Diabetes management in patients with kidney failure treated with replacement therapy/dialysis (KFRT) is challenging (1). In addition, the majority (>60%) of patients with diabetes and KFRT are treated with insulin, predisposing them to hypoglycemia (2). As a result, patients with diabetes and KFRT experience higher rates of severe hypoglycemia (2) compared with other high-risk groups. Glucagon should be prescribed to patients at risk for hypoglycemic events (<54 mg/dL) or hypoglycemic events requiring assistance from another person to revert severe episodes, with the goal of preventing emergency department visits, hospitalizations, and mortality (3). However, glucagon is rarely prescribed in the general diabetes population (4). Consequently, we examined national trends in glucagon fills among U.S. adults with diabetes and KFRT.

We retrospectively analyzed data between 1 January 2013 and 31 December 2017 from the U.S. Renal Data System (5). This study was deemed exempt by the Mayo Clinic institutional review board. We included adults (≥18 years old) with diabetes (ascertained using Healthcare Effectiveness Data and Information Set criteria [4]) and KFRT for ≥3 months. Diabetes type was categorized as previously described based on diagnosis codes and medication claims (4). Glucagon prescriptions rates were identified from pharmacy claims during each calendar quarter and calculated as a proportion of patients treated with antidiabetes medications. We further stratified glucagon fills by diabetes type, insulin regimen, and insulin/medication class. Change in prescriptions over time was assessed using a χ2 test between the adjusted rates in 2013 and 2017.

Among 254,195 U.S. adults with diabetes and KFRT included, 27,538 (12.14%) had type 1 diabetes and 226,657 (87.85%) had type 2 diabetes. Median age was 62.0 (IQR 50.0–70.0) years, 47.1% were women, 49% were non-Hispanic White, 25.7% were non-Hispanic Black, and 19.9% were Hispanic. Most patients lived in the southern region of the U.S. (38.9%) and were receiving hemodialysis (88.4%). The most prevalent comorbidities were hypertension (50.2%), heart failure (20.0%), neuropathy (22.9%), and retinopathy (17.2%). Overall quarterly rates of glucagon prescriptions decreased from 1.73% in 2013 to 1.46% in 2017 (P < 0.001). Among patients with type 1 diabetes, quarterly glucagon prescription rates remained stable from 3.72 to 3.50% (P = 0.37), and decreased among patients with type 2 diabetes, from 1.44 to 1.28% during the study period (P < 0.001) (Fig. 1). Among patients with type 1 diabetes, glucagon prescription rates among those treated with basal/bolus analog insulins ranged between 1.7 and 1.3% (P not significant). Glucagon fill rates among patients treated with other regimens were all <0.7% during the study period. Among patients with type 2 diabetes, glucagon prescription rates remained low in those treated with basal/bolus analog insulin (range 0.5–0.6% of patients per quarter). Quarterly glucagon fill rates among all other patients were very low (all <0.2%).

Figure 1

Glucagon prescriptions in patients with KFRT and type 1 diabetes (T1D) and type 2 diabetes (T2D). Q, quarter.

Figure 1

Glucagon prescriptions in patients with KFRT and type 1 diabetes (T1D) and type 2 diabetes (T2D). Q, quarter.

Close modal

U.S. adults with diabetes and KFRT have among the highest rates of severe hypoglycemia requiring emergency care or hospitalization (2). Clinical practice guidelines recommend prescribing glucagon (the antidote of insulin) for emergency treatment of severe hypoglycemia to all patients at risk for these events (3). Despite this recommendation, and of utmost concern, we found that only ∼3.5% of these high-risk patients with type 1 diabetes and <1.5% of these patients with type 2 diabetes filled glucagon prescriptions per calendar quarter, with declining fill rates over time.

Emergency department visits and hospitalizations for and mortality from severe hypoglycemic events are preventable, particularly with the use of glucagon (3). Electronic medical record interventions, with well-designed best practice advisory prompts and targeting of high-risk populations, have demonstrated increases in coprescription of naloxone, the antidote for opioids, changes in clinician behaviors, and decreases high-dose prescriptions (6). Future studies should assess similar interventions for glucagon in the KFRT population.

Our study is limited by reliance on claims data and lack of information on whether patients were prescribed glucagon but did not fill it or were never prescribed it in the first place. We also could not identify reasons for these low rates. Because of very low overall fill rates, subgroup analyses by patient characteristics could not be performed, though our work in the general diabetes population identified racial, ethnic, and income-based disparities in glucagon fills (4). Consistent with these disparities, we observed lower rates among those using human insulin, which may represent a population less likely to have access to care and medications. In conclusion, our findings of low rates of glucagon prescriptions in this high-risk group for hypoglycemia is a call to action for multipronged strategies targeted toward clinicians, patients, professional societies, payers, and advocacy groups.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the U.S. government.

Funding. This work was supported by National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants P30DK111024 (to R.J.G.), K23DK123384 (to R.J.G.), and K23DK114497 (to R.G.M.). G.E.U. is partly supported by NIH/National Center for Advancing Translational Sciences clinical and translational science award UL1TR002378, and both G.E.U. and M.K.A. are partially supported by NIH/NIDDK grant 1P30DK111024-01. R.G.M. is also supported by NIDDK grant R03DK127010, National Institute on Aging grant R01AG079113, National Center for Advancing Translational Sciences grant UL1TR002377, and Patient-Centered Outcomes Research Institute grants DB-2020C2-20306 and PCS-1409-24099.

The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Data were aggregated into groups, and cells with <11 individuals or <5 providers or facilities were omitted per U.S. Renal Data System (USRDS) guidance. The data reported here have been supplied by the USRDS under a user agreement. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of U.S. government.

Duality of Interest. R.J.G. received research support to Emory University for investigator-initiated studies from Novo Nordisk, Dexcom, and Eli Lilly and consulting fees, advisory board fees, and honoraria from Sanofi, Eli Lilly, Novo Nordisk, Pfizer, Merck, Boehringer Ingleheim, and Weight Watchers outside of this work. G.E.U. has received unrestricted research support for research studies to Emory University from Dexcom, Abbott, Bayer, and AstraZeneca. M.K.A. has received grant support to Emory University from Merck and received consulting fees from Bayer and Eli Lilly, all outside the scope of this work. K.R.T. is supported by NIH research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, and UM1AI109568 and Centers for Disease Control and Prevention project number 75D301-21-P-12254 and reports other support from Eli Lilly and Gilead, personal fees and other support from Boehringer Ingelheim and AstraZeneca; grants, personal fees, and other support from Bayer and Novo Nordisk, grants and other support from Goldfinch Bio, and grants from Travere outside the submitted work. No other potential conflicts of interest relevant to this article were reported.

Author Contributions. R.J.G. drafted the initial manuscript. R.J.G., S.A.I., G.E.U., B.M., J.M.M., M.K.A., K.R.T., and R.G.M. contributed to the study concept and design, interpretation of data, and critical revision of the manuscript for important intellectual content. R.J.G., S.A.I., and R.G.M. contributed to the data acquisition and analysis. R.J.G. and R.G.M. developed the study’s concept and initial protocol and obtained funding. S.A.I. performed the statistical analyses. R.J.G., and R.G.M. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

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