Effects of Diabetes Duration on Cardiorenal Efficacy of GLP-1 Analogs

Human kidney cross section
Human kidney cross section
Liraglutide and semaglutide demonstrated cardiorenal efficacy regardless of diabetes duration.

Diabetes duration increases risk for cardiorenal effects developing, according to study results presented at the American College of Cardiology’s Annual Scientific Session held March 16-18, 2019, in New Orleans, Louisiana. Additionally, both glucagon-like peptide-1 analogs liraglutide and semaglutide appear to reduce risk for cardiorenal outcomes effectively regardless of diabetes duration.

The LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) and SUSTAIN-6 trials (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) demonstrated that glucagon-like peptide-1 receptor agonists liraglutide and semaglutide reduce cardiovascular risk in patients with type 2 diabetes (T2D).

To investigate the effects of T2D duration on the cardiorenal efficacy of liraglutide and semaglutide, researchers conducted a post-hoc analysis of LEADER and SUSTAIN-6 in which 9340 participants with T2D and high cardiovascular risk were randomly assigned to receive liraglutide or semaglutide and 3297 were assigned to a placebo group.

Patients were categorized as having a diabetes duration <5 years, 5 to <15 years, 15 to <25 years, or ≥25 years. The primary end point was a composite of a major adverse cardiovascular event (MACE), defined as nonfatal myocardial infarction, stroke, or cardiovascular death. Secondary outcomes measured nephropathy and other major cardiovascular events.

The results indicated that patients with a longer duration of T2D were older, more often women, and had worse renal function and higher rates of peripheral artery disease and insulin use.

Diabetes duration was positively associated with frequency of nephropathy as well as with all adverse cardiovascular events examined in the study. Compared with placebo, use of liraglutide across the spectrum of diabetes duration reduced the risk for MACE (hazard ratio [HR] range, 0.70-0.90), nephropathy (HR range, 0.71-0.90), and other cardiovascular events (HR range, 0.78-0.91).

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In a similar fashion, patients receiving semaglutide were at reduced risk for MACE (HR range, 0.61-0.90), nephropathy (HR range, 0.47-0.79), and other cardiovascular events (HR range, 0.65-0.88) compared with those taking placebo for all categories of T2D duration.

Based on these results, the investigators concluded that liraglutide and semaglutide were both effective in reducing cardiorenal events in T2D, even in patients with longer diabetes duration who were at increased risk.

Disclosure: Novo Nordisk funded and developed the LEADER and SUSTAIN-6 trials.

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Verma S, Bain SC, Honore JB, et al. Duration of diabetes and cardiorenal efficacy of liraglutide and semaglutide: a post hoc analysis of the LEADER and SUSTAIN-6 clinical trials. Presented at: American College of Cardiology’s 68th Annual Scientific Session; March 16-18, 2019; New Orleans, LA. Poster 1024-05.

This article originally appeared on The Cardiology Advisor