By Max Bingham, PhD
Interim Data Is Positive on Endoscopic Duodenal Mucosal Resurfacing for Type 2 Diabetes Treatment
Preliminary data from a first-in-human study of the Revita duodenal mucosal resurfacing (DMR) procedure suggest the approach might well result in significant improvement in hyperglycemia in patients with type 2 diabetes. The study by Rajagopalan et al. (p. ) presents an interim analysis of data at 6 months postprocedure from 39 type 2 diabetes patients with the suggestion of potent glycemic effects including large reductions in mean HbA1c.The endoscopic procedure involves hydrothermal ablation of the duodenal mucosa, which in short means applying heat to the mucosal cells of the duodenum. Efficacy of the treatment was then assessed via various relevant measurements including HbA1c conducted prior to the procedure and at various time points up to 6 months. Due to the workup of the procedure during the study, patients received either so-called short segment or long segment ablation. According to the authors, reductions in fasting plasma glucose were noted at 1 week and HbA1c reductions at 1 month. The effects were still reportedly present at 6 months in a majority of patients. More potent glycemic effects were present in patients that received longer segments of ablation. While the study is uncontrolled and nonrandomized, the authors rightly urge caution but remain optimistic with the study scheduled to continue for a few more years. At this stage, they say that mechanisms remain unclear but are likely linked to altered signaling following the procedure. Commenting more widely on the study, Harith Rajagopalan told Diabetes Care: “We believe these early studies show evidence of safety as well as early signs of a mechanism of action that could be a new treatment approach for people with type 2 diabetes who have failed oral medications. As we proceed with randomized clinical trials we hope to learn more about the role the duodenum plays in insulin resistance and how we can alter the progression of type 2 diabetes. Hopefully the result of this work will be a scalable alternative for patients who are frustrated by their current options.”
No Effects of Resveratrol on Insulin Sensitivity in Type 2 Diabetes: Potential Interaction With Metformin
The natural polyphenol resveratrol does not improve hepatic or peripheral insulin sensitivity in patients with type 2 diabetes that are taking metformin. This is according to a crossover study by Timmers et al. (p. ). Specifically the researchers have found that metformin might interact with resveratrol and possibly block any potential effects of the supplement. As a result, the authors conclude that resveratrol is likely to have limited value as an add-on treatment and suggest that studies on the effects of resveratrol on insulin sensitivity should be conducted in the absence of oral glucose-lowering drugs and possibly in subjects with prediabetes. The crossover-designed study focused on 17 patients with type 2 diabetes who received either placebo or 150 mg/day of resveratrol for 30 days with a washout period (30 days) in-between. Insulin sensitivity was then assessed via the gold standard hyperinsulinemic-euglycemic clamp technique—a method that the authors say has not routinely been used in other studies on resveratrol and insulin sensitivity in patients with diabetes. A range of other measures was also taken. In short, there was no difference in insulin sensitivity after either placebo or resveratrol. However, muscle lipid content increased, mitochondrial function improved, and systolic blood pressure tended to decrease after resveratrol treatment. There was also a correlation between patients’ metformin dose and plasma levels of the resveratrol metabolite, dihydroresveratrol. According to author Patrick Schrauwen: “We confirmed that resveratrol has beneficial effects on mitochondrial function and some other measures in patients with type 2 diabetes. However, these beneficial effects did not result in improvements in glucose homeostasis. Most likely, the glucose-lowering drug that patients with type 2 diabetes use overruled the effects of resveratrol, a food supplement. Therefore, food supplements like resveratrol may be better suited for the prevention and treatment of diseases in drug-naïve patients. Future studies, including long-term interventions, should reveal if this is indeed the case.”
Reduced Blood Pressure in Type 1 Diabetes and Reduced Risk of Adverse Renal Outcomes
Lower blood pressure in type 1 diabetes may be associated with a reduced risk of adverse renal events, according to Ku et al. (p. ). Moreover, increased blood pressure may also increase risk of such events, prompting calls for current recommendations on blood pressure to be reviewed. Using data from the Diabetes Control and Complications Trial (DCCT) and its long-term follow-up the Epidemiology of Diabetes Interventions and Complications (EDIC), the authors looked at the relationship between systolic and diastolic blood pressures and a range of renal outcomes, including macroalbuminuria and stage III chronic kidney disease (the primary outcomes). The study involved just over 1,000 participants and follow-up of ∼24 years. In comparison to the reference systolic blood pressure level (130 to <140 mmHg, the recommended level in diabetes), they found substantially lower risk for both outcomes associated with lower blood pressure (<120 mmHg). The opposite was true with much higher blood pressure levels. Similar trends were also evident with diastolic blood pressure as well as for more minor adverse renal events such as microalbuminuria and declining glomerular filtration rate. Perhaps significantly, there was no interaction between any measure of blood pressure and the original assignment of patients to either conventional glycemic control therapy or the intensive regime (part of the original DCCT trial), suggesting that the effect of lowering blood pressure independently modified risk of adverse renal outcomes. Recently devised recommendations on blood pressure in both type 1 and 2 diabetes have increased the levels from <130/80 to <140/90 mmHg on the basis of a lack of solid trial-based evidence that there was any benefit to patients. But, as the authors state, that recommendation was based mostly on data exclusively related to type 2 diabetes. Commenting more widely on the outcomes, author Elaine Ku said: “We believe our results further inform the current debate with regards to optimal blood pressure targets in patients with type 1 diabetes and highlight the need for trials dedicated to this specific population.”
Sitagliptin Has No Effect on Long-term Adverse Cardiovascular or Chronic Kidney Disease Outcomes: TECOS Trial Update
Sitagliptin, a dipeptidyl peptidase-4 inhibitor used to help control and lower glucose levels in type 2 diabetes, has no clinically significant effects on cardiovascular or chronic kidney disease (CKD) outcomes—an outcome likely to support its continued use in the treatment of diabetes. The findings come from a post-hoc analysis by Cornel et al. (p. ) of TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin), a trial that did indeed show that adding sitagliptin to regular diabetes treatments did not increase the risk of major adverse cardiovascular events. However, what is not clear is the effect of the drug on cardiovascular and CKD outcomes in participants with impaired kidney function. Using data from 14,671 TECOS participants, the authors evaluated both outcomes over a 3-year period with patients categorized according to their estimated glomerular filtration rate (eGFR) category, a measure of kidney function. They report that there was a relationship between eGFR category and cardiovascular outcomes with lower baseline eGFR corresponding to increased incidence of a composite outcome of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Individual components of this composite outcome largely followed the same pattern. However, when comparing the sitagliptin and placebo groups, the patterns where not different. Sitagliptin was not associated with any difference in cardiovascular outcomes for any eGFR stage. Kidney function also declined at about the same rate in both groups, although with a marginally lower but constant eGFR difference in the sitagliptin group, which the researchers say is likely not going to have any significant clinical impact. In short, they conclude that sitagliptin is not inferior to placebo in terms of cardiovascular or CKD outcomes. Author Rury R. Holman commented further on the study: “TECOS shows that further analyses of data from large-scale randomized controlled trials can provide additional insights that can reassure patients and help guide clinical practice.”
