Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) in People With Diabetes: The Need for Screening and Early Intervention. A Consensus Report of the American Diabetes Association Free

Until recently, liver health has been somewhat overlooked in the context of prediabetes and type 2 diabetes. The growing prevalence and serious health implications of metabolic dysfunction–associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease (NAFLD), have prompted a call to action by the American Diabetes Association (ADA). The overarching goal of this consensus report is to provide guidance to health care professionals for the care and prevention of liver disease for people with prediabetes or diabetes.

Table 1 summarizes the clinical implications for adults with prediabetes or diabetes of having MASLD. In the U.S., the prevalence of MASLD among people with type 2 diabetes is ≥70%, with approximately half having the more progressive form with metabolic dysfunction–associated steatohepatitis (MASH) and about one in five having advanced liver fibrosis (1–3). Similar trends are observed worldwide in adults with type 2 diabetes (4–6). The presence of MASH markedly increases the risk of developing liver-related complications such as cirrhosis, hepatocellular carcinoma (HCC), and overall mortality. MASLD is one of the most common indications for liver transplantation in the U.S. (7), and having type 2 diabetes is independently associated with higher posttransplantation mortality, especially after kidney transplantation (8). Having MASLD significantly increases the likelihood of developing type 2 diabetes, cardiovascular disease, and extrahepatic malignancies (6). Finally, MASLD has a major negative impact on health-related quality of life and has become a significant economic burden (9).

Despite these alarming trends, a significant lack of awareness remains among both people at risk and clinicians regarding the health perils associated with MASLD and how best to manage it, often resulting in the condition being overlooked and untreated. There is a pressing need for heightened awareness, early diagnosis, and comprehensive management. This consensus report aims to address this knowledge gap with a clinical care pathway to manage people with prediabetes or diabetes and MASLD. Health care professionals must recognize that an early diagnosis is possible by using noninvasive tests (NITs) to stratify people for their risk of developing cirrhosis. A timely diagnosis can encourage the adoption of healthier lifestyle habits or the initiation of pharmacological treatments for obesity and type 2 diabetes, which can prevent disease progression and, ultimately, cirrhosis. Numerous medications are currently under development to treat MASH. In 2024 the U.S. Food and Drug Administration approved resmetirom as the first pharmacological agent for people with MASH (10). Improvements in steatohepatitis and liver fibrosis were reported with semaglutide after 72 weeks of treatment in a phase 3 clinical trial, supporting an upcoming indication for MASH (11).

This guidance also covers the best practices for monitoring MASLD once diagnosed or in response to treatment. Because managing both hepatic and extrahepatic conditions associated with diabetes and MASLD is challenging, this guidance recommends the development of interprofessional teams that support the primary care physician and endocrinologist, including professionals such as registered dietitian nutritionists (RDNs), diabetes care and education specialists (DCES), behavioral health specialists, obesity management teams, pharmacists, hepatologists, and other specialists. Currently, numerous health care barriers hinder the delivery of optimal person-centered care for MASLD in primary care settings (12). This guidance also discusses integrating management pathways into electronic medical records (EMRs) to enhance care and the impact of alcohol intake on liver health and provides considerations for managing diabetes in individuals with cirrhosis and HCC.

Cirrhosis from MASLD is preventable in people with diabetes through early diagnosis, proper treatment, and long-term monitoring, similar to the management of care for diabetes-related microvascular complications (retinopathy, nephropathy, or neuropathy) or cardiovascular disease. With increased clinician awareness and action, individualized education, more effective care models, and robust public health policies (13,14), we aim to catalyze a shift in clinical practice that will improve outcomes and the quality of life of people with diabetes and MASLD.

The ADA convened a technical expert panel of health care professionals who play a key role in the prevention and management of diabetes and MASLD, and an experienced member of the panel was chosen as a chair to lead the development of the report. Panelist inclusion was based on excellence in clinical care, research, leadership, collaboration, and writing and editing; commitment to evidence-based practice; and availability to volunteer (unpaid) for the report development process. The number of panelists was chosen based on consideration of the health care professionals likely to be included as a part of diabetes and MASLD care teams (e.g., primary care physicians, endocrinologists, hepatologists, behavioral health specialists, obesity management specialists, RDNs, DCES, etc.). ADA solicited nominations from the pool of experts on record and from other relevant societies. ADA led the selection process and invited the experts to join this panel. In the event of invited panel members opting not to participate, the subsequent nominee on the list was invited. A preliminary version of this report was presented at the ADA 84th Scientific Sessions, and public feedback received during and after that session was incorporated into the subsequent versions of this report.

Prior to the initiation of evidence review and writing, the panel was convened in a virtual meeting and agreed on the proposed goal, content, methodology, and rigor to be followed for this consensus report. An additional virtual meeting was held for discussion of subsections and writing teams to contribute to the sections of the report. The technical expert panel, with the assistance of a methodologist, conducted literature searches in PubMed and the Cochrane Library using related medical subject headings and terms to identify studies published in English through April 2024. The literature search was updated in November 2024. To identify appropriate evidence, the panel prioritized information from systematic reviews, randomized controlled trials, and observational studies. Questions related to clinical practice and interprofessional team collaboration for the prevention and care of liver disease in people with diabetes or prediabetes provide the foundation of this report. This document includes recent information about nomenclature and clinical definition, epidemiology, diagnosis, treatment, and topics of special consideration (e.g., development of interprofessional teams, cirrhosis, and alcohol intake).

Monthly virtual meetings were held between December 2023 and November 2024 along with email and Web-based collaboration as needed. An in-person meeting was conducted in April 2024 to finalize discussion of evidence, reach consensus on the present guidance, discuss the tables and graphic design elements, and finalize writing content. Meetings were recorded, and meeting summaries were provided to panel members via an online collaboration platform and email.

This consensus guidance was developed under the auspices of ADA and represents the technical expert panel’s collective analysis and evaluation. ADA and the panel were committed to fostering a collaborative environment of respectful communication. Panel members were asked to focus on evidence-based discussion and clinical judgement rather than personal opinions or biases, which warranted supplying supporting evidence for their discussions. ADA scientific team members were present for all discussions and helped ensure that all perspectives were taken into account. These principles were conducive to mitigating conflict, respectful discussion, and consensus building.

The nominal group technique was used to reach consensus on the guidance presented in this document, which was facilitated by the consensus report chair and the ADA scientific team. Topic areas and questions were posed to the full group by the chair and other panel members during virtual and in-person meetings. The panel used discussion in a roundtable or similar fashion to take all ideas into account. These discussions were carried out in detail so as to clarify meaning, resolve questions and/or clarifications, and bring forth new ideas. The technical expert panel collectively finalized the topic areas and reached consensus on the guidance covered in this document in a nonanonymous group setting during the virtual and in-person meetings, where each member “agreed” or “strongly agreed” in a rotating sequence, ensuring that all voices were heard before a decision was made. Verbal responses were aggregated in real time during these meetings and in written fashion from comments on collaborative documents. At the end of each meeting, the panel members were provided with qualitative summaries, including topic areas for which consensus was reached and topics that required further attention on an ongoing basis.

The nominal group technique presented several strengths and some limitations. This methodology was used to encourage equal participation by all panel members and to facilitate discussion of diverse ideas. This allowed the panel to discuss viewpoints of all members of the interprofessional care team. Though this methodology had its advantages, time periodically posed a concern. Every effort was made to give topics ample time for deliberation. Complex topics were given priority at meetings to allow full discussion of insights and perspectives. The qualitative meeting summaries shared with the panel after each meeting allowed for reflection and opportunity to bring forth further discussion points throughout the development of the report until consensus on these topics was reached.

Table 2 summarizes the current nomenclature with the most relevant clinical definitions. In Supplementary Table 1, we describe the mortality risk associated with each liver disease stage, the most commonly used NITs, and the optimal setting for health care professionals managing care for people with MASLD.

Three multinational liver associations recently agreed to modify the nomenclature from NAFLD to MASLD (15). MASLD was defined as steatotic liver disease (SLD) in the presence of at least one cardiometabolic risk factor (such as prediabetes or type 2 diabetes) without other identifiable secondary cause of steatosis (15) (Fig. 1). Likewise, the term nonalcoholic steatohepatitis (NASH) has been replaced with MASH (15). The aim of the new names (MASLD and MASH) is to highlight the pathogenic role of insulin resistance and metabolic dysfunction, remove any potential stigma from the terms nonalcoholic and fatty, and serve as a pragmatic diagnostic aid by virtue of inclusion of at least one of the cardiometabolic risk factors in the definition, these being already well known to the health care community in the context of metabolic syndrome and type 2 diabetes.

Table 3 summarizes the contributions of the new terminology and current knowledge gaps. There is a high correlation between NAFLD and MASLD in population-based studies (16–18). In comparing their concordance among 12,519 eligible participants from the National Health and Nutrition Examination Survey (NHANES) III, only 5.3% of NAFLD cases did not meet MASLD criteria. Of 6,429 adults with NAFLD, 99% met MASLD criteria, with 95% doing so on the basis of BMI only (17). The high concordance between NAFLD and MASLD is attributable to the very high prevalence of overweight or obesity in the general population and that 85% of adults, even without steatosis, have at least one cardiometabolic risk factor (18).

Prediabetes and diabetes are now identified as important cardiometabolic risk factors for the development of MASLD, advanced fibrosis, and cirrhosis (19). However, randomized controlled trials (RCTs) will be needed for understanding of the role of hyperglycemia in the development and progression of MASLD, as findings of some studies have been of an association between suboptimal glycemic management and steatosis or fibrosis (20), while in others either a modest or no association was observed (4,21). In addition, there are no RCTs on the role of optimal glycemic management in liver outcomes in MASLD, independent of improving insulin resistance (e.g., with pioglitazone) or promoting weight loss (e.g., glucagon-like peptide 1 receptor agonists [GLP-1RA]). It must also be recognized that diabetes encompasses a spectrum of etiologies, including many where insulin deficiency rather than insulin resistance predominates (e.g., type 1 diabetes, cystic fibrosis–related diabetes, and pancreatogenic diabetes, along with others) and where the risk of steatohepatitis with clinically significant fibrosis is overall low (4,22). Recent studies have identified novel diabetes subtypes that appear more prone to development of MASLD (23). With factors taken together, future studies should include risk stratification and careful assessment of the natural history of MASLD in individuals with different subtypes of diabetes.

Several additional aspects of adopting the new nomenclature should be considered (24). Future studies should be conducted for examination of the relative specificity of each cardiometabolic risk factor included in the definition of MASLD to predict liver outcomes. Type 2 diabetes and obesity among them have the strongest diagnostic concordance with MASLD and atherogenic dyslipidemia has the least. One should bear in mind that some of these cardiometabolic risk factors may develop through mechanisms unrelated to insulin resistance (25) and, under such circumstances, be of less value for consideration in association with MASLD. Nevertheless, linking steatosis with these cardiometabolic risk factors may improve clinicians’ disease awareness and referral patterns, which deserve future investigation. Clinicians should be careful in attributing steatosis to MASLD by virtue of the presence of one of these cardiometabolic risk factors and be aware of alternate causes of steatosis, for many of which specific therapies are available. (See diagnostic considerations in section 3. diagnosis and Supplementary Table 2). Finally, while recent data confirm that obesity worsens the risk of hepatic fibrosis in young adults (aged 18–44 years) with type 2 diabetes (26), at the other end of the spectrum young adults may have isolated steatosis with insulin resistance without obesity or evident cardiometabolic disease (27). Clinicians should not miss the opportunity for these individuals with presumable “early” MASLD to risk stratify and encourage lifestyle intervention.

The perception of stigma arising from obesity, and in some cases from the term fatty in NAFLD, affects a significant number of people with this disease and is highly variable among affected individuals and their clinicians and across geographic regions (28). While the new nomenclature MASLD may function to reduce stigma, much work remains in eliminating additional contributing factors. Finally, a separate category named MetALD has been created for individuals with MASLD and an alcohol intake that is greater than that for MASLD classification but less than in alcohol-associated liver disease (ALD) (15) (Fig. 1). Future studies will be needed to help determine its natural history and the impact of lifestyle interventions and pharmacotherapy to prevent cirrhosis from MetALD.

MASLD has become the most common cause of chronic liver disease, affecting >38% (2016–2019) of the world’s adult population and 7%–14% of children and adolescents (6,29). The prevalence of MASH among the general population is estimated at 5%–7%, while the prevalence of MASLD-related cirrhosis is 1.8% (6). These rates are much higher in people with type 2 diabetes, with estimated prevalence of ∼70% for MASLD, ∼35% for MASH, and ∼7% for MASLD-related cirrhosis (1–6,30,31).

Recent data also suggest that the prevalence of MASLD among those with prediabetes is between ∼37% and 50% (32). In fact, people with prediabetes are 2.5 times more likely than those without prediabetes to have MASLD, 8.5 times more likely to have significant fibrosis, and almost 6 times more likely to have advanced fibrosis (32).

The incidence rate of MASLD has been reported to be 49 per 1,000 person-years (6). The bidirectional association of type 2 diabetes and MASLD is suggested by the twofold higher incidence of type 2 diabetes among those with MASLD (33,34). The most important predictors for prediabetes and type 2 diabetes are having overweight or obesity and MASLD (34).

Additionally, having type 2 diabetes is associated with an increased relative risk of fibrosis progression (35–37), while 15%–38% of people with type 2 diabetes have MASH with clinically significant liver fibrosis or cirrhosis (also known as at-risk MASH [see fibrosis stage definitions in Table 2 and Supplementary Table 1]) (1–6,26,31,38). The presence of MASLD has been associated with increased incidence of other metabolic-related diseases such as cardiovascular disease (43% increase), prediabetes (69%), chronic kidney disease (38%), and all cancers (54%) (39).

Beyond metabolic comorbidities, diverse genetic, environmental, and socioeconomic determinants of health explain the heterogeneous prevalence of MASLD around the world. In people with type 2 diabetes, the prevalence of MASLD is highest in Eastern Europe (80%), followed by the Middle East (71%), and lowest in Africa (53%) (40). In the U.S., MASLD prevalence differs by ethnicity and is highest for Hispanic, especially Mexican American, and lowest for Black individuals. These differences are most likely explained by differences in acquired risk factors (e.g., prevalence of obesity, diabetes, and socioeconomic determinants of health) and the genetic polymorphisms of PNPLA3, TM6SF2, and MBOAT, among others (41). The prevalence of MASLD usually increases among men until age 50 years; then, risk for women begins to be higher for MASH and advanced fibrosis (42). In this context, MASH can cause a significant burden for women and is currently the number one cause of liver transplantation among women (43). Lastly, socioeconomic disparities also exist for MASLD disease burden. In particular, food insecurity (the limited or uncertain access to nutritionally adequate foods) is associated with higher odds among adults of developing MASLD and MASLD‐associated advanced fibrosis independent of poverty status, education level, race, and ethnicity (44). Similar findings were reported among teenagers from food insecure homes (45).

Although the presence of liver fibrosis is the most significant predictor of mortality for those with MASLD, it is well known that the severity of metabolic abnormalities, especially in the case of type 2 diabetes, is a major driver of mortality among MASLD (30,32). In this context, the presence of an increasing number of metabolic abnormalities leads to increasing risk of mortality in MASLD, with the highest risk of mortality among people with type 2 diabetes (4.0-fold increase in risk) followed by those with prediabetes (3.4-fold increase in risk) (32).

In addition to cirrhosis, HCC is an important consequence of MASLD. Although the presence of cirrhosis in MASLD substantially increases the risk of HCC, those with MASLD without cirrhosis can also develop HCC (46). In this context, as type 2 diabetes predisposes to MASLD, diabetes seems to be a risk factor for developing HCC. Dysregulated glucose homeostasis, hyperinsulinemia, and lipid accumulation in the liver can activate pathways promoting hepatic tumor development in individuals with MASLD and type 2 diabetes (37,38). MASH-related HCC is now the number one indication for liver transplantation among those listed for HCC (47). In the context of liver transplant, it is important to note that the presence of diabetes prior to transplant, the receipt of a liver from a donor with diabetes, or developing diabetes posttransplant are all associated with higher risk of mortality and graft loss (48).

In addition to the clinical outcomes, MASLD is also associated with decreased health-related quality of life. The ability to be physically active is the domain most adversely affected, possibly due to fatigue (49). Finally, MASLD has significant economic consequences for society due to increased health care use and decreased quality of life, particularly among those with more metabolic comorbidities (49).

The rationale for any screening strategy is applying adequate diagnostic tools to eventually treat a condition that may lead to serious morbidity and mortality. This is the case for people with type 2 diabetes with at-risk MASH (defined as steatohepatitis with clinically significant fibrosis or fibrosis stage ≥2) (50,51) (Table 2 and Supplementary Table 1). In at-risk MASH, hepatic fibrosis is the target of screening because it is the most important determinant of liver and non-liver outcomes in people with MASLD, with the risk demonstrably higher for people with at-risk MASH (52). Several professional societies (53–58), including the ADA (59), recommend screening high-risk individuals for at-risk MASH to prevent fibrosis progression and cirrhosis. Screening followed by intensive lifestyle intervention or pioglitazone has been suggested to be cost-effective (60).

Diagnosing hepatic steatosis begins with obtaining a medical history and laboratory testing. While a liver ultrasound has in the past been widely used to diagnose hepatic steatosis, the presence of an echogenic liver itself is not highly specific, as its diagnosis is operator dependent and ultrasound has poor sensitivity for mild steatosis (61). Because having obesity and prediabetes or type 2 diabetes is associated with a high pretest probability of hepatic steatosis (≥70%) (1–6), one may proceed directly to fibrosis risk assessment without an ultrasound to confirm steatosis. (See prevalence of masld in prediabetes and type 2 diabetes according to world region and ethnicity.) Further, management is impacted by the diagnosis of clinically significant fibrosis and not by the diagnosis of steatosis per se. Therefore, the focus has shifted toward detection of fibrosis severity (i.e., at-risk MASH), which is closely linked to the risk of clinical outcomes (Supplementary Table 1 and Fig. 2). Within the workup to establish the presence of fibrosis, or as part of secondary testing when there is diagnostic uncertainty because of abnormal plasma aminotransferases (ALT or AST), steatosis can be diagnosed with the controlled attenuation parameter from a vibration-controlled transient elastography (VCTE) examination. Values >280 dB/m are highly likely indicative of having steatosis. MRI is the gold standard for confirmation of steatosis (i.e., MRI-derived proton density fat fraction PDFF [MRI-PDFF] or ¹H-MRS) (62,63).

Some individuals may have abnormal plasma aminotransferase levels. In people with MASLD, having an elevated ALT level is suggestive of steatohepatitis but not necessarily of more severe liver fibrosis or cirrhosis (1,64–66). In such cases, alternate causes of liver disease, such as hepatitis B or C and ALD, need to be excluded (Supplementary Table 2). The Centers for Disease Control and Prevention recommend universal screening at least once for hepatitis B (67) and C (68) for all adults >18 years of age. Hepatitis C is now curable in virtually all individuals. Alcohol consumption is widespread in many communities and has a synergistic effect with obesity for liver-related morbidity and mortality. All clinicians should be able to perform an alcohol-related liver disease assessment (Supplementary Table 3). The presence of both, metabolic risk factors and alcohol use (20–50 g/day for women and 30–60 g/day for men), should be considered indicative of the possibility of underlying MetALD (Fig. 1). People who consume alcohol regularly should be counseled, with appropriate management. (See section 8. alcohol intake and liver health.) Workup of uncommon causes of increased plasma aminotransferase levels may require referral to a liver specialist (Supplementary Table 3).

Another important consideration is awareness by the health care team about how to best deliver the diagnosis of MASLD as it may affect a person’s acceptance of their condition and their ability to manage it. Thus, engaging in a clear, open conversation to explain the clinical implications of MASLD is essential. Understanding and acceptance of their condition often allow for adoption of proactive and problem-solving coping strategies that may reduce psychosocial concerns and support engagement in lifestyle modification and the treatment plan.

Adults with type 2 diabetes should undergo a two-tier process for assessment for diagnosing at-risk MASH because fibrosis stage reflects proximity to development of liver cirrhosis and is thus a strong prognostic biomarker. Figure 2 summarizes the preferred NITs for the initial and secondary fibrosis risk stratification and optimal management setting for people at high risk for MASLD. (See also Supplementary Table 1 and Table 4.)

The first step in this two-tier process begins with laboratory testing, which should include a comprehensive metabolic panel and complete blood count; plasma aminotransferase levels (ALT and AST), platelet count, and age allow for calculation of a simple noninvasive marker of liver fibrosis, the fibrosis-4 index (FIB-4) (Fig. 2 and Table 4). FIB-4 as the first-tier test has several advantages: it is simple and inexpensive to use, a robust negative predictive value of a FIB-4 score for exclusion of advanced fibrosis (69,70), and, most importantly, test results at baseline as well as longitudinal changes in FIB-4 predict clinical outcomes in people with MASLD (71–76), including in individuals with type 2 diabetes (77). In a recent comparative study, overall diagnostic accuracy of FIB-4 was found to be similar to that of most other proprietary and nonproprietary biomarkers among individuals with biopsy-confirmed MASLD included in the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) cohort (78).

A FIB-4 score <1.3 can reliably be used to exclude advanced fibrosis (Fig. 2), with a negative predictive value of ≥90% (69). Individuals with values below this cutoff do not need further evaluation (in particular, with a FIB-4 score <1.0). With age as a contributor to the FIB-4 score calculation, its performance may be affected for people ≤35 or ≥65 years of age. One study recommended using a cutoff of 2.0 to rule out clinically significant fibrosis in people ≥65 years old (57). However, there are limited data that confirm the 2.0 cutoff. Hence, we suggest using a simplified approach that relies on a threshold of 1.3 for considering a second-tier test (79,80).

Approximately 30%–40% of individuals with obesity and prediabetes or type 2 diabetes may have a FIB-4 score >1.3, and they should undergo a second test for further risk stratification as part of the two-tier approach (1–3). Individuals with a FIB-4 score >2.67 (≤5% of individuals with type 2 diabetes in nonhepatology settings) are at increased risk for advanced fibrosis, with a positive predictive value for clinically significant fibrosis ranging from 60% to 80% (81). These individuals can be directly referred (without the need of additional risk stratification at the primary care level) to gastroenterologists and hepatologists to assess for the presence of at-risk MASH or cirrhosis (Fig. 2). Most clinical care pathways endorse the use of liver stiffness measurement (LSM), most commonly with transient elastography (VCTE), as the second step in the two-tier approach (Fig. 2). A stepwise FIB-4 plus VCTE–based algorithm performed well in stratifying the risk of future liver-related events in a recent multicenter cohort (80). A VCTE-derived LSM of <8.0 kPa rules out advanced fibrosis accurately most times (81) and is associated with a low risk of liver outcomes (82,83), and people with LSM <8.0 kPa should be followed in primary care and endocrinology clinics with repeat surveillance in 1–2 years (see Long-term Monitoring). Individuals with LSM >8.0 kPa should be referred to gastroenterology or hepatology specialists for additional diagnostic testing. Shear wave elastography, point shear wave elastography, and other ultrasound-based methods can also be used for initial risk stratification, but they are not as well validated as VCTE.

The Enhanced Liver Fibrosis (ELF) test can also be used as a second-tier test (84) (Fig. 2, Supplementary Table 1, and Table 4). ELF is a noninvasive blood-based proprietary test approved for prognostication when advanced fibrosis is suspected, although it can be ordered for secondary risk assessment, particularly because the availability of VCTE may be limited in some settings. The ELF test includes a panel of biomarkers consisting of three components: type III procollagen peptide, hyaluronic acid, and tissue inhibitor of metalloproteinase-1. An ELF score <7.7 is associated with a very low risk of fibrosis, whereas a score ≥9.8 helps identify people with MASLD with advanced fibrosis and at increased risk of progression to cirrhosis and liver-related clinical events (85–88). An ELF score >11.3 is associated with the highest risk of hepatic decompensation events, and such cases are best managed in a hepatology setting (89,90). ELF has proven useful in guiding referrals in primary care and diabetes clinic populations (91,92). An ELF score <9.8 suggests a low risk of advanced liver fibrosis, which may be followed in primary care or endocrinology settings with repeat testing at ≥2 years. Individuals with ELF score ≥9.8 should be referred for secondary assessment due to the increased risk of liver-related events. Of note, the optimal ELF cutoff for use in nonhepatology clinics is evolving; management decisions should be individualized when the ELF score is between 9.2 and 9.7 based on clinical risk (i.e., testing may be needed more often in a high-risk individual with multiple cardiometabolic risk factors).

Individuals with a FIB-4 score >1.3 and VCTE-derived LSM ≥8.0 kPa or an ELF score ≥9.8 should be considered for referral to liver specialty clinics (gastroenterology or hepatology) for additional assessment (Fig. 2). In liver clinic settings, imaging-based methods are usually used for better estimation of the fibrosis stage, including magnetic resonance elastography (MRE) (93) or multiparametric MRI-derived iron-corrected T1 (cT1) (which may identify people with at-risk MASH) (94). In head-to-head comparisons, MRE has higher accuracy in detecting liver fibrosis, especially in earlier stages, than VCTE (95–97). While MRE may not be the initial choice for risk stratification due to cost and access considerations, it can serve as a valuable tool in specialty clinics, especially in cases of uncertainty or unreliable VCTE results. VCTE-derived LSM >10 kPa and MRE-derived LSM >3.5 kPa suggest advanced fibrosis (i.e., liver fibrosis stages 3 [F3] and 4 [F4]) and a value >15 kPa and MRE values >4.4 kPa are consistent with a high probability of cirrhosis (i.e., stage F4) (98). VCTE-derived LSM >25 kPa (99), VCTE-derived LSM >20 kPa with platelet counts ≤150,000/mm³, and MRE-derived LSM >5.7 kPa are all reflective of likely having clinically significant portal hypertension (100) (Supplementary Table 1).

Liver biopsy is generally considered when noninvasive assessments are inconclusive or when alternative diagnoses are suspected. NIT results that may improve identification of advanced fibrosis or cirrhosis among individuals attending liver clinics and decrease the need for liver biopsy include transient elastography–based scores such as Agile 3+ (VCTE-LSM combined with AST-to-ALT ratio, platelet count, sex, diabetes status, and age) or Agile 4 (VCTE-LSM combined with AST-to-ALT ratio and platelet count for diagnosis of cirrhosis) (101–103), MRE-based measures such as MRI-AST (MAST) score (MRE plus AST) or MEFIB index (MRE plus FIB-4) (104,105), and used more recently to identify at-risk MASH, results from blood-based proprietary tests such as NIS2+ score (from a two-biomarker test derived from YKL-40 and miR-34a-5p corrected for sex) (102,103) or Metabolomics-Advanced Steatohepatitis Fibrosis Score (MASEF score) (a metabolomics-driven score) (106) and MRI-derived cT1 (94) (Supplementary Table 1).

The chronic nature and fluctuating course of MASLD require monitoring of the disease state in affected individuals. There is also a high possibility of de novo development of MASLD in individuals with diabetes, supporting the need for monitoring individuals without MASLD at the initial evaluation. Initiation of therapy also requires follow-up to assess treatment response. The best evidence-based guidance is summarized below.

A growing body of literature indicates that most individuals with a FIB-4 score <1.3 are unlikely to have increased liver-related outcomes or mortality within a 5-year time frame (76,107,108). These individuals may therefore be considered relatively low-risk, and management is usually focused on optimization of body weight, diabetes management, and underlying risk factors. However, there are limited data on how often to repeat FIB-4 testing because the natural history of fibrosis progression in MASH is not fully established and is highly variable among people with type 2 diabetes. In a prospective study from Hong Kong with use of repeated imaging (VCTE), worsening in LSM was found in 12% of participants after 3 years of follow-up (109). Of note, FIB-4 is a low-cost test with acceptable negative predictive value but with modest sensitivity and positive predictive value. With factors taken together, we recommend that individuals with an initial FIB-4 score <1.3 be reassessed with repeat FIB-4 measurements in 1–2 years. Clinically significant fibrosis may be present in some adults with type 2 diabetes and FIB-4 values between 1.0 and 1.3, especially when type 2 diabetes is associated with obesity and multiple cardiometabolic risk factors. For instance, in a recent large phase 3 study with recruitment of people with MASLD with fibrosis stages F2 and F3, often with obesity and type 2 diabetes, the mean ± SD of the FIB-4 score was 1.4 ± 0.7 (10). This indicates that for some individuals with at-risk MASH FIB-4 score may be <1.3, especially in the context of obesity and type 2 diabetes. Therefore, a FIB-4 score cutoff of <1.3 should be taken as a general guidance for assessment of having a lower risk of advanced fibrosis, but it does not replace clinical judgement. Case finding with eventual additional testing may be justified with a FIB-4 score between 1.0 and 1.3 in people with type 2 diabetes with obesity or other traditional cardiometabolic risk factors. For these cases transient elastography may also be of benefit as part of risk assessment. The risk of developing MASLD has been independently associated with insulin resistance, weight gain, obesity, and cardiometabolic risk factors (110–112). In contrast, individuals with type 2 diabetes without MASLD often have less insulin resistance and a more favorable cardiometabolic profile in comparison with those with steatosis (113,114).

Once MASH with fibrosis develops, progression to more advanced stages is believed to occur at an average rate of 7 years per stage progression (115). Therefore, those whose FIB-4 score increases from <1.3 to >1.3 should be referred for transient elastography. Given the potential for underestimation of fibrosis severity in those with type 2 diabetes, those who progress from <1.0 to values between 1.0 and 1.3 may also be considered for secondary assessment with VCTE or an ELF test (74–84).

In the majority (>90%) of people from primary care and endocrinology clinics, a FIB-4 score >1.3 will range between 1.3 and 2.67. A FIB-4 score between 1.3 and 2.67 was initially considered indicative of “indeterminate risk” for having advanced fibrosis, reflecting the score range between a high-sensitivity cutoff for ruling out (FIB-4 score <1.3) and a high-specificity cutoff for ruling in (FIB-4 score >2.67) advanced fibrosis (116). However, more recent studies directly relating FIB-4 score between 1.3 and 2.67 to clinical outcomes indicate that, for people either with or without type 2 diabetes, rates of death, liver-related deaths, liver outcomes, and cardiovascular disease are higher among those with a FIB-4 score between 1.3 and 2.67 than among those with a FIB-4 score <1.3 (76). Because of this increased risk of negative outcomes, it is recommended that for people with a FIB-4 score >1.3 risk stratification with transient elastography be considered a requirement, as discussed above.

People with a FIB-4 score >1.3 but VCTE-LSM <8.0 kPa can be followed in non-liver specialty clinics with repeat surveillance in 1–2 years. Most guidelines (53–59) recommend LSM by VCTE as the leading disease monitoring tool, as it predicts future outcomes (83,117). In a global cohort of >16,000 individuals, an increase in VCTE-LSM by ≥30% was associated with increased risk of adverse clinical outcomes (83). The transient elastography–based FibroScan-AST (FAST) score, for detection of at-risk MASH, and the Agile scores, for detection of advanced fibrosis or cirrhosis (Supplementary Table 1), are additional scores that may be helpful in this regard (83,101,118,119). For these elastography-based scores VCTE-LSM is combined with routine blood parameters and clinical features. Although not representative of a substantial diagnostic improvement, these scores may help reduce the number of people with inconclusive results from VCTE-LSM alone (83,101,118,119).

People with a FIB-4 score >1.3 and VCTE-LSM >8.0 kPa should undergo more diagnostic testing in gastroenterology or hepatology specialty clinics for confirmation of at-risk MASH or cirrhosis. In individuals with cirrhosis, an increase in liver stiffness and a decrease in platelet counts to <150,000 are associated with development of portal hypertension, which is a key driver of clinical decompensation (99). Annual transient elastography along with platelet counts may be considered for this subgroup. Screening for HCC and assessment of Model for End-Stage Liver Disease (MELD) score and complication(s) of portal hypertension should be performed every 6 months in individuals with cirrhosis to ensure timely diagnosis of HCC and referral for liver transplant for a rising MELD score, particularly to values of ≥15.

Individuals with a FIB-4 score >2.67 at initial evaluation are at high risk for advanced fibrosis, liver-related outcomes, and all-cause mortality. Approximately 3%–5% of people with type 2 diabetes and MASLD may have an initial FIB-4 score >2.67 (1–3). Such individuals can be directly referred to gastroenterologists or hepatologists for evaluation of the presence or absence of cirrhosis and initiation of cirrhosis-related care for HCC surveillance, to prevent decompensation and delay the need for liver transplant, if indicated.

As the disease progresses, people with type 2 diabetes and MASLD may experience increased frustrations and worries about their future. The interprofessional team should consider screening for depressive symptoms and anxiety. As complications dominate, people need to learn to live with challenges that impact their usual level of activity and feeling of well-being.

Individuals with a FIB-4 score >1.3 and a second test (i.e., VCTE-LSM) confirming at-risk MASH may receive treatment for obesity or type 2 diabetes (e.g., GLP-1RA, dual glucose-dependent insulinotropic polypeptide [GIP] and GLP-1 receptor agonist [dual GIP/GLP-1RA], or pioglitazone) that may also impact underlying MASH, or they may receive treatment specifically targeting MASH (e.g., resmetirom or semaglutide). FIB-4 is not very sensitive to fibrosis change, and its increase or decrease only occurs after substantial changes in fibrosis stage (69). Furthermore, short-term improvement (6–12 months) in FIB-4 likely reflects changes in inflammation (i.e., plasma aminotransferases) rather than fibrosis. On the other hand, several studies have shown that liver stiffness measures improve after effective drug intervention, and sustained improvement has been reported in clinical trial settings (120). These data support the use of transient elastography (VCTE-LSM) to evaluate responses to therapeutic intervention. Improvement by ≥30% represents therapeutic response, whereas an increase by ≥30% reflects disease progression (83). Referral to the gastroenterologist or hepatologist is warranted if there is a suggestion of disease progression.

The value of EMR-integrated clinical decision support tools in MASLD is multifaceted. EMR use facilitates the incorporation of MASLD clinical practice guidelines into the clinical workflow. EMRs with FIB-4 scores can engage people through granting access to their data, empowering them in their health care journey. In EMR systems FIB-4 calculation can be automated, streamlining risk stratification in clinical practice (121). This can serve as a decision support tool in flagging people with high FIB-4 scores for further evaluation, aiding early detection, secondary testing, and referrals to the liver specialist and other members of the MASLD interprofessional team. EMR integration can assist in disease monitoring and tracking disease progression over time, providing insights for optimizing medical care. Additionally, this integration can contribute to research and population health management, from understanding the natural history of the disease in the “real world” to assessing the role of different lifestyle interventions and pharmacotherapy.

Overall, EMR-integrated clinical decision support tools will play an important role for busy clinicians in screening implementation for high-risk individuals and improve clinical outcomes.

Management of MASLD in adults involves an interprofessional team including but not limited to primary care physicians, endocrinologists, nurses, RDNs, DCES, behavioral health specialists, obesity management teams, pharmacists, and liver and other medical specialists. The comprehensive care plan includes lifestyle modification, weight management, and pharmacological treatment aimed at preventing cardiovascular disease and MASH cirrhosis (59).

A healthy lifestyle is the foundation of treatment in people with type 2 diabetes and MASLD. Figure 3 summarizes a broad spectrum of useful lifestyle interventions. In people with overweight and obesity, the magnitude of weight loss correlates overall with improved glycemic management, insulin sensitivity, and histological improvement in MASH, including fibrosis (122,123). Among people with MASH, weight loss of ≥5% of total body weight decreases steatosis. Weight loss of >5% usually is needed to reverse steatohepatitis (56,122,124,125). Many studies suggest that even more weight reduction (≥10%) is needed to improve fibrosis and that the response can be highly variable (56,57,122,124). Of note, improvement in liver histology may be seen with lesser degrees of weight loss and, conversely, only modest improvement with significant weight loss.

When lifestyle modification includes individualized nutrition diagnosis, treatment, and behavior modification recommendations, it should be delivered by an RDN. However, all health care team members can reinforce general nutrition guidance. Furthermore, it is essential to use appropriate psychosocial care methods and provide access to diabetes self-management education and support (DSMES) services as a critical part of healthy lifestyle interventions for people with type 2 diabetes and MASLD (126).

Nutrition plans should be tailored to the individual’s social, work, cultural, and financial context and provided in a practical, implementable format. Given that MASLD often clusters in families, and family support is crucial for success, family counseling should be included (69). Evidence suggests that no ideal calorie percentage from carbohydrates, proteins, and fats can be broadly recommended for all people with prediabetes or diabetes (127). However, nutrition plans high in saturated fat and sugar (from sucrose and/or high-fructose corn syrup) are associated with postprandial hypertriglyceridemia, insulin resistance, and higher risk of MASLD or MASH with fibrosis progression in high-risk individuals (122,128). Increased fructose consumption is associated with fibrosis severity, independent of total caloric intake (128). In macronutrient distribution avoidance of ultraprocessed foods and reduction in saturated fat and simple sugars and fructose consumption should be emphasized, as should an eating pattern enriched with high fiber and unsaturated fats (56,57,126,127).

Various nutritional approaches (e.g., low fat vs. low carbohydrate, Mediterranean diet, Dietary Approaches to Stop Hypertension [DASH] diet, high protein, meal replacement, and intermittent fasting, among others) seem comparable in their ability to improve steatosis (129,130), but their benefit for steatohepatitis and fibrosis have not been adequately studied (122). A (culturally appropriate) Mediterranean eating pattern (rich in fruits, vegetables, whole grains, and heart healthy fats) is preferred due to the best long-term data on beneficial cardiometabolic risk factor reduction and mortality benefit (122,129–131) and is endorsed in current MASLD guidelines (55,56,58,59,122).

Alcohol consumption increases the risk of cirrhosis and HCC (132). It should be avoided in individuals with at-risk MASH. (See section 8. alcohol intake and liver health.)

Structured exercise has been shown to decrease insulin resistance, plasma aminotransferases, and steatosis in individuals with MASLD (133–136). Different exercise types and intensities can produce different outcomes, with aerobic activity potentially offering greater hepatic benefits than other types (133,134) and high-intensity activity improving MASH and fibrosis (137).

Although current guidelines recommend accumulating at least 150 min of moderate- or 75 min of vigorous-intensity activity weekly and performing resistance activities two to three times per week for individuals with diabetes or MASLD or MASH (126,138), care teams should personalize activity plans based on individual needs, goals, and preferences as well as provide resources to support activity self-efficacy and long-term adoption (126). Minimizing sedentary time and engaging in brief sessions (∼10 min) of simple activities such as walking with the goal of meeting activity guidelines should be encouraged (126). Resistance training may prevent sarcopenia and functional decline (133,139).

Psychosocial care should be provided to all people with type 2 diabetes and MASLD to optimize health-related quality of life. There is a lack of large, high-quality studies for evidence-based best treatment recommendations for depression, anxiety, binge eating disorder, serious mental illness, or substance use, specifically in MASLD (140). Drawing from the type 2 diabetes literature, evidence-based approaches include cognitive behavioral therapy, mindfulness-based therapy, and/or pharmacotherapy (126). All may be of help to treat mental health issues in adults with diabetes and MASLD that often overlap with obesity and its comorbidities, as well as with the use of obesogenic psychiatric medications. Behavioral health professionals should monitor outcomes systematically to assess progress and ongoing needs.

DSMES services provided by a DCES have been shown to support behavior change in people with type 2 diabetes. DSMES should be offered at least annually to people with type 2 diabetes and MASLD (for more details, refer to ADA “Standards of Care in Diabetes—2025” [Standards of Care] [126]). While basic healthy eating guidance is provided during DSMES sessions, coordination with the RDN ensures that specific nutrition therapy related to the person’s liver disease is addressed (141).

Although there are limited data on behavioral weight loss interventions in MASLD (142), structured nutrition and exercise intervention in addition to health education should be offered to all people with MASLD (57,126,143–145). These interventions share similarities with strategies for the management of obesity and for the prevention and treatment of type 2 diabetes (146). Literacy about fibrosis stage and risk of MASLD progression may improve adherence to lifestyle intervention (147–149).

Together with lifestyle optimization, pharmacotherapy should always be considered in the management of people with diabetes with overweight or obesity and MASLD. Lifestyle modification alone often is unable to achieve or maintain long-term weight loss of the magnitude usually recommended to reverse steatohepatitis and fibrosis (>10%) (56,57,122).

Pharmacological therapy for obesity in MASLD should be individualized, potential risk-benefit and cost considered, and treatment strategies reassessed often over time. Figure 4 summarizes the management of MASLD in considering the severity of liver disease and the pharmacological options for obesity or type 2 diabetes with potential to reverse steatohepatitis, as well as MASH-specific therapies (i.e., resmetirom). GLP-1RA reduce cardiovascular disease, the main cause of death in MASLD (150), and offer renal protection to people with type 2 diabetes (see ADA Standards of Care [151,152]). Certain GLP-1RA also reduce cardiovascular disease in individuals without diabetes with overweight or obesity and preexisting cardiovascular disease (153).

At present, no obesity pharmacotherapy has an approved indication for MASLD, but GLP-1RA have reported positive results in phase 2 RCTs and a phase 3 RCT. In a phase 2 RCT where 320 participants with MASH (65% with type 2 diabetes) received treatment with semaglutide, a GLP-1RA, MASH resolution without worsening of fibrosis occurred in 59% of individuals vs. 17% on placebo (P < 0.001). Fibrosis did not improve (43% in the 0.4-mg group vs. 33% in the placebo group, respectively, P = 0.48), but fewer individuals on semaglutide had worsening of fibrosis at 72 weeks (4.9% in the 0.4-mg group vs. 18.8% in the placebo group) (154). Recently, the phase 3 Effect of Semaglutide in Subjects with Non-cirrhotic Non-alcoholic Steatohepatitis (ESSENCE) trial in 800 participants with MASH (11) reported that for 36.8% of individuals treated for 72 weeks with semaglutide 2.4 mg s.c. once weekly improvement in liver fibrosis was achieved with no worsening of steatohepatitis, compared with 22.4% on placebo (P < 0.001), while 62.9% achieved resolution of steatohepatitis with no worsening of liver fibrosis, compared with 34.3% on placebo (P < 0.001) (11).

Tirzepatide, a dual GIP/GLP-1RA, has also been studied for the treatment of MASH. In an early study in adults with type 2 diabetes and MASLD, it had been reported that 52 weeks of treatment decreased liver fat by up to 47%, compared with 11% with insulin degludec (P < 0.001) (155). In the phase 2 SYNERGY-NASH trial, treatment of 190 adults with overweight or obesity and MASH (50%–60% with diabetes) for 52 weeks with tirzepatide at doses of 5, 10, and 15 mg/day resulted in resolution of steatohepatitis without worsening of fibrosis in 44%, 56%, and 62% of participants, respectively, compared with 10% with administration of placebo (P < 0.001 for all three comparisons) (156). The percentage of participants with an improvement of at least one fibrosis stage without worsening of MASH was 55%, 51%, and 51% of participants, respectively, compared with 30% with placebo. Finally, in an early proof-of-concept trial in individuals with MASH, the GLP-1RA liraglutide at a mean daily dose of 1.3 mg/day was reported to have positive results after 48 weeks of treatment. MASH resolution occurred in 9 of 23 (39%) participants who were treated with liraglutide, compared with 2 of 22 (9%) in the placebo group (P = 0.019) (157). Progression of fibrosis was seen in only 9% of those who received liraglutide compared with 36% in the placebo group (P = 0.04).

Promising dual and triple agonists in the pipeline also include survodutide, a dual glucagon and GLP-1 receptor agonist. In 295 participants with overweight or obesity and MASH (clinical trial reg. no. NCT04771273, ClinicalTrials.gov), all doses of survodutide (2.4, 4.8, and 6.0 mg/day) met the primary outcome: a decrease of at least 2 points in NAFLD activity score without worsening of fibrosis, as well as MASH resolution. At the highest dose, significant improvement in liver fibrosis was seen in individuals with at-risk MASH (P < 0.001) (158). Tests are also ongoing of retatrutide, a triple GIP receptor agonist, GLP-1RA, and glucagon receptor agonist, for the management of MASH. In phase 2 trials, retatrutide induced dose-dependent weight loss in people with type 2 diabetes (159) or obesity (160). In a subset of 98 people with obesity and MASLD (≥10% liver fat, assessed with MRI-PDFF), the higher dose of retatrutide (12 mg s.c. once weekly) normalized liver fat in 90% of participants at the higher doses and improved biomarkers of steatohepatitis after 48 weeks of treatment (161).

For other U.S. Food and Drug Administration–approved weight management agents, i.e., orlistat (an oral lipase inhibitor), centrally acting oral combinations such as phentermine/topiramate ER or naltrexone/bupropion ER, or daily liraglutide 3 mg s.c., rigorous histological evidence of benefit in MASH is lacking, although they may reduce plasma aminotransferases or steatosis in the case of significant weight loss (56,162). There have been reports from several clinical trials that liraglutide at doses used to treat diabetes (up to 1.8 mg) or obesity (3.0 mg) (163,164) ameliorate steatosis, along with a report from a 48-week pilot study of histological improvement (157).

Metabolic (also termed bariatric) surgery in people with diabetes improves glycemic management, promotes diabetes remission (165), and prevents cardiovascular disease (146,166–168). Metabolic surgery improves steatosis in 70%–80% of individuals, with resolution of inflammation and hepatocyte ballooning (necrosis) in 50%–75% and fibrosis in 30%–40% (169,170). Metabolic surgery also reduces the risk of HCC (170,171) and other cancers (171). Although most data are from case-control observational studies, in an RCT in 288 adults with biopsy-confirmed MASH, lifestyle modification plus best medical care was compared with Roux-en-Y gastric bypass or sleeve gastrectomy (172). The primary outcome of resolution of MASH without worsening of fibrosis at 1 year of follow-up was achieved in 56% and 57% of the Roux-en-Y gastric bypass and sleeve gastrectomy groups, respectively, compared with 16% with lifestyle modification (P < 0.0001). Among participants who completed the trial (82%), the primary outcome with either type of surgery was met in 70% of participants, compared with 19% with lifestyle modification (P < 0.0001).

The long-term benefit of metabolic surgery for the treatment of MASH is possibly best illustrated with an observational study where 606 adults with obesity and MASH, but without cirrhosis, were matched to a nonsurgical control group (n = 550) and followed for a median of 7 years (172). The metabolic surgery group showed more favorable long-term outcomes compared with the nonsurgical group, including significantly lower major adverse liver outcome occurrence (2.3% vs. 9.6%, respectively, P = 0.01) and a significant reduction in cardiovascular events (8.5% vs. 15.7%, respectively, P = 0.007). Thus, metabolic surgery can significantly reduce the risk of cirrhosis and cardiovascular disease, although lack of significant weight loss is associated with failure to reverse steatohepatitis or fibrosis. Endoscopic metabolic surgeries are less invasive options, but more robust evidence is needed for recommendations for their use to treat obesity in adults with MASLD (56,57).

Metabolic surgery should be recommended with caution in compensated cirrhosis from MASLD (i.e., asymptomatic stage of cirrhosis without associated liver complications), as the risk of hepatic decompensation appears comparable with that for individuals with less advanced liver disease when performed in experienced centers with interprofessional teams (173,174). However, long-term studies are needed to better establish the safety and efficacy of metabolic surgeries and which type is best. There is significantly less information on procedures in people with clinically significant portal hypertension or decompensated cirrhosis (i.e., with complications such as variceal hemorrhage, ascites, hepatic encephalopathy, or jaundice), but overall these conditions are associated with worse outcomes and metabolic surgery should only be considered together with liver transplantation in tertiary centers. Therefore, metabolic surgery is not recommended in decompensated cirrhosis, given the limited outcome data available and the higher risk of postoperative liver-related complications (55–57).

Approximately 15%–20% of adults with type 2 diabetes (1,2,4,21,175) have at-risk MASH and are on a path to develop cirrhosis if untreated (1,2,4,21,176,177). This high prevalence is comparable with or higher than that for other diabetes-related complications such as diabetic nephropathy, retinopathy, or neuropathy. Although no glucose-lowering medication is approved for the treatment of MASLD, preference in treating diabetes should be given to those treatments with evidence of safety and effectiveness for steatohepatitis from high-quality phase 2 RCTs and a phase 3 RCT (e.g., GLP-1RA and/or pioglitazone, or dual GIP/GLP-1RA tirzepatide), with the dual purpose of treating hyperglycemia and steatohepatitis (154,178,179) (Fig. 4). Once cirrhosis is established there are currently no effective treatments. Table 5 summarizes our current knowledge about the effect of glucose-lowering medications in MASLD as well as their cardiorenal benefit.

As discussed above in pharmacological treatment of obesity in masld, semaglutide (11,154), tirzepatide (156), and liraglutide (157) improve MASLD in individuals without cirrhosis. Still, their long-term safety, tolerability, and efficacy remain to be established. The combination of gastrointestinal side effects, formulation as injectables, and high cost may limit long-term treatment adherence. Real-world data suggest discontinuation rates of ∼50% and ∼60% at 12 and 24 months, respectively—usually higher with daily versus weekly GLP-1RA dosing (180,181).

Pioglitazone may reverse steatohepatitis in people without diabetes (182–185) or with prediabetes or type 2 diabetes (186,187) (Table 5). The effect on fibrosis is modest; the placebo-subtracted proportion of people with improvement in fibrosis among different studies ranges from 9% to 22% (statistically significant in none) (182–187). Studies have been relatively small and underpowered for this outcome. Still, in some studies, fewer individuals exhibit fibrosis progression in comparison with placebo (185,187), and in a meta-analysis of available studies investigators concluded that pioglitazone may improve fibrosis (178). As a generic medication, pioglitazone may be a cost-effective alternative for the dual purpose of treating type 2 diabetes and MASH (60). Dose-dependent weight gain can be mitigated by prescribing lower doses (15 mg/day, weight gain 1%–2%) (188–190). Net weight loss is observed when pioglitazone is combined with a GLP-1RA (191–196) or a sodium–glucose cotransporter 2 (SGLT2) inhibitor (194,197–200). In addition, combined pioglitazone and GLP-1RA treatment is associated with a greater decrease in hepatic steatosis as compared with pioglitazone alone in people with type 2 diabetes (196,201). Pioglitazone improves left ventricular function (194,202) but may promote heart failure if inadvertently prescribed to individuals with preexisting congestive heart failure. Dose- and time-dependent increases in risk of fractures and bladder cancer have been reported, although the data for bladder cancer remain controversial (203).

Vitamin E may be considered for the treatment of MASH in selected individuals without diabetes (182), with effects significantly impacted by haptoglobin genotype (204), although when used in combination with pioglitazone in adults with diabetes it did not enhance pioglitazone’s efficacy in comparison with earlier studies with the thiazolidinedione, and there is not enough evidence at this time for recommendation for people with type 2 diabetes (55–58,205). In a retrospective study in individuals with MASH and advanced fibrosis, it was reported that vitamin E was associated with less disease progression (206). However, controversy remains about a potential increase in hemorrhagic stroke and prostate cancer (207).

In at least six phase 2 RCTs, SGLT2 inhibitors were tested in individuals with type 2 diabetes and MASLD (dapagliflozin, empagliflozin, and canagliflozin, and smaller studies with others), and modest reductions in hepatic steatosis were consistently reported (e.g., mean of ∼20% placebo-subtracted relative decrease in intrahepatic triglycerides) (164) (Table 5). Modest benefit was reported in an open-label trial with liver histological outcomes (208), while in another no improvement was noted (209). In a recent prospective study in 237 people with type 2 diabetes from diabetes clinics, with a mean follow up of ∼4.5 years, it was reported that use of SGLT2 inhibitors was associated with less fibrosis progression (liver stiffness measured with transient elastography) (210). SGLT2 inhibitors have not been rigorously tested with histological outcomes in MASH, but their cardiometabolic benefits make them an attractive option for people with MASLD.

Glucose-lowering agents other than pioglitazone or GLP-1RA or dual GIP/GLP-1RA can be continued for glycemic management, as clinically indicated, but may not improve MASH (i.e., metformin) (56,57) or have not been tested in MASH in paired liver biopsy trials (i.e., insulin, sulfonylureas, dipeptidyl peptidase 4 [DPP-4] inhibitors, meglitinides, or acarbose) (Table 5).

The prevalence of MASLD is increasing among people with type 1 diabetes, especially when associated with obesity (211), and weight gain appears to be linked to insulin resistance, hyperglycemia, and more difficult to manage diabetes (212). In one study an only 8% prevalence of steatosis was reported, measured with MRI, in adults with type 1 diabetes predominantly without obesity compared with an eightfold higher prevalence in those with type 2 diabetes (liver fibrosis was not measured) (213). A meta-analysis from 29 studies, including 390 individuals with type 1 diabetes and 10,487 individuals with type 2 diabetes, reported prevalence rates of fibrosis, measured with transient elastography, of 5.2% and 19.8%, respectively (4). The current recommendation is to screen for fibrosis in people with type 1 diabetes only in the context of risk factors for MASLD, in particular obesity, elevated plasma aminotransferases, or steatosis as an incidental finding (56,59). Treatment should focus on lifestyle modification that induces weight loss in individuals with overweight or obesity. Optimizing glycemic management with insulin therapy may reduce steatosis (155,164,214). Other diabetes medications (or resmetirom) have not been tested in this population.

Resmetirom is a selective thyroid hormone receptor β (THR-β) agonist (215), approved in early 2024 for the treatment of MASH with fibrosis stages F2 and F3. Its THR-β isoform selectivity (a receptor isoform with expression predominately in liver, kidney, pituitary, and brain tissue) minimizes potential undesirable off-target THR-α–related effects in heart and bone tissues. Resmetirom decreases steatosis through not yet fully understood mechanisms such as enhancing mitochondrial function and improving the hepatic conversion of thyroxine (T4) to triiodothyronine. Administration for 52 weeks in 966 adults randomized 1:1:1 to oral resmetirom at a dose of 80 mg or 100 mg or placebo led to MASH resolution in up to 29.9% of participants receiving resmetirom compared with 9.7% on placebo (P < 0.001) (10). Fibrosis improved in up to 25.9% and 14.2%, respectively (P < 0.001). Treatment initiation does not require a liver biopsy, and specific guidance has been developed for identification with NITs of adults with MASH with fibrosis stages F2 and F3 (i.e., LSM by imaging with VCTE or MRE) for whom therapy is suitable (216). Main exclusion criteria are compensated or decompensated cirrhosis, active liver diseases (i.e., autoimmune hepatitis or primary biliary cholangitis), suboptimally managed hypothyroidism or hyperthyroidism, or ongoing alcohol consumption of >20 g/day for women or >30 g/day for men. Nausea, vomiting, and diarrhea are the most frequent adverse events with resmetirom therapy. Resmetirom may lower free T4 levels by ∼20% and increase two- to threefold sex hormone–binding globulin (SHBG) protein levels (10,216). Increasing SHBG in the setting of borderline or frank hypogonadism has the potential to exacerbate hypogonadism because it may alter the dynamics between bound and free testosterone, resulting in a decrease in biologically active hormone. Also, SHBG can potentially deliver testosterone directly to tissues with unknown biological effects on androgen-dependent organs (63,217). The long-term clinical significance of these hormonal changes remains to be determined (218). Baseline thyroid function testing prior to initiating therapy is recommended by the American Association for the Study of Liver Diseases (AASLD) (216), as hypothyroidism is common in the general population (∼12%) and steatosis may be associated with hypothyroidism (55). Monitoring of thyroid function during resmetirom therapy should be based on clinical judgement. Of note, some people during the phase 3 trial had free T4 levels below normal (most often transient), needed resmetirom dose adjustments, or were started on levothyroxine (219). Because hypogonadism develops more often in older adults and in those with MASLD, clinicians should follow current guidelines (56,122,124) that recommend the evaluation of symptomatic individuals for hypogonadism on the basis of a fasting total testosterone and free testosterone concentration (ideally with liquid chromatography–mass spectrometry and equilibrium dialysis, respectively) (220) or consider an endocrinology consult.

There is limited information on combining resmetirom with medications often used for comorbidities in MASLD (e.g., pioglitazone, GLP-1RA, or dual GIP/GLP-1RA). People with obesity and type 2 diabetes should make it a priority to optimize lifestyle and medical management with a GLP-1RA, pioglitazone, or their combination or a dual GIP/GLP-1RA (tirzepatide) with potential benefits for steatohepatitis (59). Addition of resmetirom should be initiated by a hepatologist or gastroenterologist with expertise in MASH and within the context of an interprofessional team approach, cost-benefit assessment, and individual decision sharing. In monitoring resmetirom treatment recent guidance by AASLD should be followed (216).

MASLD in type 2 diabetes is best managed by a coordinated health care team with expertise to address prevention, screening, diagnosis, lifestyle interventions, medication, and monitoring, led by the primary care physician (Fig. 5). Depending on the disease stage, location, and resources in the area, the health care team may vary and even include expertise accessed remotely. Prevention is a critical first step, requiring awareness and expertise in managing diet, exercise, and obesity at the primary care level with support from dietitians, exercise physiologists, and behavioral health care professionals. Pharmacists can help by screening for obesogenic medications and suggesting pharmacologic interventions for obesity if appropriate. Diagnosis of early disease and eventual referral to a gastroenterologist or hepatologist, as per the diagnostic algorithm in Fig. 2, should become a routine component of type 2 diabetes care. A diagnosis of at-risk MASH may motivate behavior change and may be helpful for individuals for obtaining insurance coverage for more intensive behavioral and medical interventions.

Other valuable team members include obesity specialists in established weight loss programs and medical exercise programs, such as for cardiovascular or pulmonary rehabilitation. Mental health treatment and referral to behavioral health specialists can aid people with type 2 diabetes and MASLD who struggle with depression (140), which can hinder behavior change and weight loss (Fig. 5). Suboptimally managed hyperglycemia should be managed with the combined efforts of an endocrinologist and diabetes educator. Even after an individual progresses to advanced fibrosis or cirrhosis and is under a liver specialist’s care, the primary care and interprofessional teams must remain involved for management of behavioral and nutritional care and care for cardiometabolic risk factors and other MASLD-related comorbidities (56,57,59,126).

The endocrinologist/diabetes care specialist is essential in managing MASLD in people with type 2 diabetes (56,57,221). Given the increased risk of cardiometabolic complications (150,222,223) and advanced liver fibrosis in this population (1,21), these professionals are at the front line of recognizing MASLD and treating its comorbidities (224). MASLD is found to occur more often in people attending diabetes clinics in comparison with primary care, possibly because long-standing type 2 diabetes is much more common. Therefore, the endocrinologist is in a unique position to 1) lead efforts to screen and risk stratify people at risk (Fig. 2), 2) promote lifestyle changes (Fig. 3) and initiate medications that benefit people with type 2 diabetes and MASLD (56,57) (Fig. 4), 3) develop interprofessional teams and manage referrals for optimal care (Fig. 5), and 4) stay engaged in the long-term follow-up of people with MASLD (12,224,225).

Of note, the endocrinologist should identify and treat other conditions associated with MASLD besides type 2 diabetes commonly seen in endocrinology clinics such as obesity (including secondary causes, e.g., Cushing syndrome), polycystic ovary syndrome, hypothyroidism (215), hypogonadism (frequent in older males), hypopituitarism, severe hypertriglyceridemia, and lipodystrophy (including that associated with HIV/highly active antiretroviral therapy), among others. The endocrinologist is often the first in line to exclude MASLD and diagnose secondary causes of liver disease (Supplementary Table 2).

Timely and appropriately structured lifestyle interventions remain crucial, with emphasis on weight loss as the principal strategy. Summary of pharmacological choices for obesity in MASLD in Fig. 4 and Table 5 follows the ADA Standards of Care that recommend weight loss using a GLP-1RA or a dual GIP/GLP-1RA (59).

As discussed earlier, metabolic surgery is recommended for suitable candidates, albeit with caution advised for people with compensated cirrhosis, and is not recommended in hepatic decompensated cirrhosis (59). Thus, a multifaceted approach involving lifestyle changes, pharmacotherapy, and potentially surgery is key to managing the intertwined issues of type 2 diabetes, obesity, and MASLD, with the aim of preventing progression to more severe liver diseases.

DSMES is valuable in providing general nutritional recommendations as part of its comprehensive curriculum (141). We further recommend referral to an RDN to deliver medical nutrition therapy that can target the specific metabolic conditions relevant to each individual (226). There are several unique considerations for RDNs in caring for people with type 2 diabetes and MASLD. Even when a patient does not have elevated plasma aminotransferases, RDNs need to consider whether at-risk MASH may be present in developing nutrition care plans for any adult within the high-risk groups, such as those with obesity, prediabetes, or type 2 diabetes or with a medical history of steatosis. Such plans should be formulated with the aim of managing weight, attaining glycemic goals, and addressing cardiometabolic risk factors to prevent hepatic and extrahepatic outcomes (57).

RDNs and DCES should consider a FIB-4 score calculation, if all components are available, for risk stratification and a better understanding of, along with educating people on, the importance of medical nutrition therapy for a person’s liver health. Additionally, alcohol impacts both energy balance and disease progression, so suspicion of effects of alcohol should trigger an alcohol-related liver disease assessment (Supplementary Table 3) and be addressed during counseling sessions. (See section 8. alcohol intake and liver health.) Finally, communication with the referring provider about risk stratification, nutrition care plans, liver health outcomes, and new health conditions is essential to long-term success.

The behavioral modification team plays a foundational role in managing MASLD in people with diabetes in terms of both prevention and disease management. Primary care physicians and other clinicians can access additional support for lifestyle interventions through various behavioral health team members, including exercise physiologists, behavioral health professionals, and DCES. These professionals offer vital expertise in physical activity programs, body composition and weight management, psychosocial concerns, diabetes distress, substance use, education promoting positive lifestyle behaviors, and overcoming barriers (Supplementary Table 4).

Gastroenterologists and hepatologists play an important role in managing clinically significant fibrosis, starting from the comprehensive fibrosis staging of the disease (clinically significant fibrosis, advanced fibrosis, or cirrhosis), then in developing stage-specific treatment plans, and then during long-term follow-up, in collaboration with other members of the interprofessional team. As mentioned in fibrosis risk stratification and referral guidelines, overview of additional tests by specialists, and role of liver biopsy, people at risk for fibrosis (based on FIB-4 or LSM scores) should be considered for referral to liver specialty clinics (gastroenterology or hepatology) where they may undergo imaging-based methods (MRE or cT1) or liver biopsy for final diagnosis. The liver specialists may also use evolving multimodal scores such as transient elastography–based scores (Agile 4 and Agile 3+), NIS2+ score (102,103), or MRE-based measures (MAST score, MEFIB index, and MASEF score) (104–106) for diagnosis of cirrhosis or advanced fibrosis.

People with cirrhosis also require ongoing HCC surveillance (liver ultrasound and α-fetoprotein), screening and primary prophylaxis for esophageal varices, and monitoring for the need for liver transplantation. Treatment of comorbidities, such as type 2 diabetes, calls for joint care with endocrinologists/diabetes specialists in determining how to best tailor diabetes treatments and monitoring response accordingly (see below).

Cirrhosis profoundly modifies the overall management of diabetes. Liver cirrhosis can worsen insulin resistance and glucose intolerance, explaining the higher prevalence of diabetes observed among people with cirrhosis (227)—highest among those with MASLD-cirrhosis or cryptogenic cirrhosis (56% and 51%, respectively) (228). In people with compensated cirrhosis, the presence of diabetes magnifies the risk for liver-related morbidity and mortality (3,20,229,230). In diabetes, many pathophysiological mechanisms have been invoked by which hyperglycemia may promote the development of MASH and progression to cirrhosis; however, these mechanisms remain poorly understood (203,231–233). Observational studies suggest lower rates of cirrhosis and adverse liver outcomes with GLP-1RA, SGLT2 inhibitors, and thiazolidinediones (234). In short-term clinical trials, glucose-lowering medications that stimulate weight loss (i.e., GLP-1RA) or improve insulin sensitivity (i.e., pioglitazone) may ameliorate steatohepatitis, and eventually fibrosis progression, during the course of treatment (164) (Table 5). However, the role of hyperglycemia per se is unclear and robust evidence of cirrhosis prevention through optimizing glycemic management is lacking.

The diagnosis of diabetes can be challenging due to chronic anemia, hypersplenism, renal insufficiency, sarcopenia, or ascites, where there may be discordance between standard tests used in the diagnosis of diabetes (i.e., fasting glucose and A1C) (235). People with cirrhosis may have normal or near-normal fasting plasma glucose levels despite the presence of prediabetes or diabetes. An oral glucose tolerance test could “unmask” diabetes in the presence of an apparently normal A1C (236).

Management of diabetes presents unique challenges as well in people with cirrhosis. The approach to managing their diabetes is conditional on the presence of compensated or decompensated cirrhosis [i.e., with impaired liver synthetic function or complication(s) of portal hypertension] (19). One aspect of clinical relevance is that MASLD may be associated with higher risk of severe hypoglycemia in adults with type 2 diabetes (237). Among people with type 2 diabetes, those with cirrhosis had a much higher risk of severe hypoglycemia and overall mortality in comparison with those without liver cirrhosis (238). As summarized in Fig. 6, several risk factors combine in cirrhosis to promote severe hypoglycemia, such as impaired renal function and cachexia, frequent need of insulin (with diminished renal clearance in chronic kidney disease), and cognitive dysfunction with diminished alertness during hypoglycemia that could be misdiagnosed and mistreated as hepatic encephalopathy. Concomitant medications, such as nonselective β-blockers for portal hypertension, may also increase the risk for impaired awareness of hypoglycemia in masking signs and symptoms (i.e., tremor, tachycardia) because they block the effects of norepinephrine. Therefore, a less stringent and individualized glycemic goal may be considered for people with decompensated cirrhosis (239).

Formation of an interprofessional team (primary care, RDN, endocrinologist/diabetes care specialist, hepatologist, and others) is the best practice for managing cirrhosis. Diabetes and nutrition education, with high protein intake (1.2–1.5 g/kg/day) and regular exercise, if feasible, may prevent sarcopenia, which is a common problem in people with cirrhosis (122,240). Education on glucagon administration to treat severe hypoglycemia, as well as the use of glucose monitoring devices (241), may decrease the overall risk of complications associated with hypoglycemia in cirrhosis from glucose-lowering medications. Continuous glucose monitoring systems await future greater use in this setting but have been validated and proven valuable in small proof-of-concept studies (241,242) and may be particularly useful in the case of having alerts for hypoglycemia.

Lifestyle modification including regular physical activity may improve diabetes, MASH (122,124), portal hypertension (243,244), and endurance and functional outcome measures in people with cirrhosis (245) and potentially decrease the risk for HCC (246,247). Compensated cirrhosis may be treated with caution using oral agents and GLP-1RA or dual incretin agonists, as in less severe stages of cirrhosis. Avoidance of sulfonylureas and metformin in the case of renal impairment is recommended due to the high risk of hypoglycemia and of lactic acidosis, respectively (248). However, rigorous long-term studies regarding the use of oral agents or GLP-1RA and dual incretin agonists in people with compensated cirrhosis are limited. Short-term (28–48 weeks) studies in people with cirrhosis suggest that GLP-1RA–based therapies may be safe and also can improve glycemic management in people with MASH (249,250). In several short-term studies SGLT2 inhibitors have safely been tested in individuals with advanced fibrosis and cirrhosis (19). Pioglitazone should be avoided in decompensated cirrhosis from MASH because it is mainly metabolized in the liver by CYPC28 and to a lesser extent by CYP3A4, and there is limited clinical experience. However, there was no increase in adverse events reported either in a meta-analysis that included adults with biopsy-proven MASH and advanced liver fibrosis or compensated cirrhosis treated with pioglitazone (178) or in a large population-based study (251). Insulin therapy is the preferred agent for the treatment of hyperglycemia in adults with type 2 diabetes with decompensated cirrhosis (59), given its safety and efficacy plus the lack of long-term data with oral agents or GLP-1RA (19). Future studies will be needed to reassess the role of different glucose-lowering medications in cirrhosis. A recent study from the Veterans Health Administration system in 16,058 individuals reported a 14% lower risk of cirrhosis with GLP-1RA treatment in comparison with DPP-4 inhibitor users (252). However, there was no benefit from GLP-1RA use in people with established cirrhosis (252).

In several retrospective and prospective studies, type 2 diabetes is independently associated with a two- to fourfold higher risk for HCC (31,177,253–257). Much of the association between diabetes and HCC may be explained by the development and progression of MASLD.

Although people with both diabetes and MASLD are among the highest-risk groups for HCC, the absolute risk of HCC is low and variable (258). Hence, current guidelines do not recommend screening for HCC in people with diabetes and MASLD unless there is evidence of cirrhosis. People with diabetes complications and/or suboptimal glycemic management, especially if they also have a high FIB-4 score, may be an important subgroup for close monitoring for future risk of cirrhosis (258,259). Duration of diabetes and other comorbid metabolic conditions also increased HCC risk in other studies.

Improved glycemic management to reduce cirrhosis and HCC burden in people with diabetes may hold promise but remains an understudied paradigm. Studies among individuals with type 2 diabetes have shown a reduction in HCC incidence with metformin but an increase with combination of metformin and a sulfonylurea or insulin, or a greater risk of HCC with oral agents combined with insulin therapy (259,260). Adequate glycemic management was associated with a 31% lower risk of HCC (259). The potential preventive effects of newer glucose-lowering medications for HCC are currently unknown, but this question warrants evaluation. While GLP-1RA, SGLT2 inhibitors, and pioglitazone are associated with lower rates of cirrhosis in population-based studies, their ability to prevent HCC is less clear (234,252,261). Overall, there is significant heterogeneity across observational studies, which, together with challenges in adjusting for multiple confounders, calls for caution in interpreting associations between diabetes medications and risk of HCC.

Initial evaluation of people with cirrhosis includes an assessment of alcohol intake (Supplementary Table 3). In people with preexisting obesity and diabetes, alcohol use has a synergistic effect for worsening insulin resistance, chronic liver injury, cirrhosis, HCC, and liver-related morbidity and mortality (132). Any alcohol use should be avoided in people with diabetes and chronic liver disease. Mild-to-moderate alcohol intake can serve as a cofactor for the development of steatohepatitis and fibrosis progression. Heavy alcohol intake may increase the risk of type 2 diabetes in genetically predisposed individuals by inducing hepatic and peripheral (i.e., muscle) insulin resistance and promoting a chronic increase in pancreatic β-cell demand. Alcohol intake can be defined as mild if <20 g/day for women and <30 g/day for men, moderate if between 21 and 39 g/day for women and between 31 and 59 g/day for men, or heavy if ≥40 g/day for women and ≥60 g/day for men. While earlier studies suggested a protective effect of alcohol use on cardiometabolic risk factors (262,263), subsequent studies of moderate alcohol use (defined broadly as >20 g/day) suggest lower odds of MASH resolution and increased risk for cirrhosis, HCC (264,265), and extrahepatic malignancies (266–268). Further, alcohol use may have a negative effect on glycemic management in people with diabetes (269,270), irrespective of the use of antidiabetes medications (271). Understanding of the impact of alcohol use (type, pattern, frequency, duration) in individuals with concomitant diabetes and liver disease is required.

It is now well established that adults with prediabetes or type 2 diabetes have the highest risk of developing MASLD. Approximately one in five people with type 2 diabetes have clinically significant fibrosis and are at high risk of developing cirrhosis from MASLD (i.e., has at-risk MASH), which is one of the leading reasons for liver transplantation in the U.S. MASLD is also associated with increased risk of HCC as well as extrahepatic malignancies and cardiovascular disease.

Individuals with prediabetes or type 2 diabetes should be risk stratified with a two-tier approach (FIB-4 ± VCTE-LSM) for assessment of their risk of having at-risk MASH with clinically significant liver fibrosis or cirrhosis. This consensus report delivers the message that timely identification and proper management can prevent the progression of fibrosis to cirrhosis in people with prediabetes and type 2 diabetes in the same way as already accepted for diabetes-related microvascular complications (retinopathy, nephropathy or neuropathy) or cardiovascular disease. With interprofessional care teams and clinician awareness and action, education, development of proper models of care, and proactive public health policies we hope to catalyze a shift in clinical practice that will improve outcomes and the quality of life of people with diabetes and MASLD.

Acknowledgments. The authors thank Alexandra M. Yacoubian (ADA) for administrative assistance and Michael Bonar (Leicester Diabetes Centre, Leicester, U.K.) and Charlie Franklin (Leicester Diabetes Centre) for figure design.

Funding. This statement was funded by ADA general revenue. C.R.R. has received honoraria for travel and speaker engagements from the ADA. M.B. has received research funding (to institution) from the ADA.

No other entity, including industry, provided support for this statement.

Duality of Interest. K.C. has received research support (to institution) from Boehringer Ingelheim, Echosens, Inventiva, Labcorp, and Perspectum. K.C. has served as a consultant for Aligos Therapeutics, Arrowhead, AstraZeneca, 89bio, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Novo Nordisk, ProSciento, Sagimet Biosciences, Siemens USA, Zealand Pharma, and Terns Pharmaceuticals. M.F.A. has received research support (to institution) from Madrigal Pharmaceuticals, 89bio, Hanmi Pharmaceutical, Gilead Sciences, and Inventiva. M.F.A. has served as a consultant or advisory board member for Novo Nordisk, Hanmi Pharmaceutical, Inventiva, Madrigal Pharmaceuticals, and 89bio. C.M.A. has served as an advisory board member for Altimmune, BioAge Labs, Biolinq, CinFina Pharma, Cowen and Company, EPG Comm, Vida, Veru, Wave Life Sciences, Form Health, Fractyl Health, Gelesis, Eli Lilly, L-Nutra, NeuroBo Pharmaceuticals, Xeno, Novo Nordisk, Nutrisystem, Optum Rx, Pain Script, Palatin, The Pursuit By You, Redesign Health, and ReShape Lifesciences. D.B. has served as a co-investigator for clinical trials with Inventiva Pharma and Boehringer Ingelheim. D.B. also attended an advisory board meeting for Boehringer Ingelheim and has received honoraria for lectures from Novo Nordisk. K.D.C. has received research funding from BPGbio, Target RWE, and Merck. K.D.C. has served as an advisory board member or instructor/speaker for Target RWE. C.R.R. has been part of a focus group with Dexcom and is part of a steering committee funded by Boehringer Ingelheim and Eli Lilly. M.R. has received funding for travel, is part of a speaker’s bureau, or served on advisory board for AstraZeneca, Boehringer Ingelheim, Echosens, Madrigal Pharmaceuticals, Merck Sharp & Dohme, Novo Nordisk, and Target RWE. A.J.S. has received consulting fees from Eli Lilly and has served as a consultant for Echosens, Abbott, Promed, GENFIT, Satellite Bio, Corcept Therapeutics, Arrowhead, Boston Pharmaceuticals, Variant, Cascade, 89bio, AstraZeneca, Alnylam Pharmaceuticals, Regeneron Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Gilead Sciences, Histoindex, Janssen, Lipocine, Madrigal Pharmaceuticals, Merck, GlaxoSmithKline, Novartis, Akero Therapeutics, Novo Nordisk, PathAI, Pfizer, Poxel, Salix Pharmaceuticals, Myovant Sciences, Median Technologies, Sequana Medical, Surrozen, Takeda Pharmaceuticals, Terns Pharmaceuticals, and Zydus Pharmaceuticals. A.J.S. has received grant funding (to institution) from AstraZeneca, Bristol-Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Mallinckrodt Pharmaceuticals, Merck, Ocelot, Novartis, and Salix Pharmaceuticals. AJ.S. has received royalties from Elsevier and UptoDate. A.J.S. also has stock options in Durect, GENFIT, Tiziana Life Sciences, and Inversago. J.H.S. has served as a consultant or advisory board member for Abbott, Bayer, Novo Nordisk, Sanofi, Eli Lilly, and Madrigal Pharmaceuticals. Z.M.Y. has received grant funding from Madrigal Pharmaceuticals and has served as a consultant for Madrigal Pharmaceuticals, Novo Nordisk, and Boehringer Ingelheim. No other potential conflicts of interest relevant to this article were reported.

Prior Presentation. Parts of this study were presented at the 84th Scientific Sessions of the ADA, Orlando, FL, 21–24 June 2024.

Handling Editors. The journal editor responsible for overseeing the review of the manuscript was John B. Buse.