Semaglutide Passes Cardiovascular Safety Test in Patients with Type 2 Diabetes

Summary and Comment |
October 5, 2016

Semaglutide Passes Cardiovascular Safety Test in Patients with Type 2 Diabetes

  1. Harlan M. Krumholz, MD, SM

With regard to clinical outcomes, findings from the SUSTAIN-6 trial not only establish noninferiority to placebo, they also suggest benefit.

  1. Harlan M. Krumholz, MD, SM

To fulfill an FDA requirement that new diabetes therapies demonstrate cardiovascular safety, investigators conducted an industry-sponsored, noninferiority trial of semaglutide, a glucagon-like peptide 1 analogue, for cardiovascular outcomes. They randomized 3297 patients aged 50 or older with type 2 diabetes to receive semaglutide (0.5 mg/week or 1.0 mg/week) or placebo for 104 weeks. All participants had either established cardiovascular disease or additional cardiovascular risk factors.

In the semaglutide group, the reduction in mean glycated hemoglobin was 1.1% and 1.4% at the lower and higher doses, compared with 0.4% in the placebo group. Mean weight loss in the semaglutide group was 3.6 kg and 4.9 kg, respectively, compared with about 0.5 kg in the placebo group. The primary composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke occurred in 6.6% of semaglutide patients and 8.9% of placebo patients (hazard ratio, 0.74; 95% confidence interval, 0.58–0.95). Mortality rates in the two groups did not differ significantly. Nephropathy was less common and diabetic retinopathy complications and gastrointestinal disorders were more common in the semaglutide group than in the placebo group.

Comment

In this study, semaglutide was noninferior to placebo with respect to cardiovascular outcomes. The surprising finding of benefit, while not prespecified, opens the intriguing possibility that this drug's effect translates to a reduction in cardiovascular risk. We may be entering an era of diabetes treatment in which the target glycated hemoglobin level matters less than the strategy used to lower glucose. I am eager to see if the results of follow-up trials validate the benefit found in this study.

Editor Disclosures at Time of Publication

  • Disclosures for Harlan M. Krumholz, MD, SM at time of publication Consultant / Advisory board United Healthcare (Advisory Board); Element Science (Consultant) Equity ImageCor; Hugo PHR Grant / Research support Agency for Healthcare Research and Quality; Food and Drug Administration; National Heart, Lung, and Blood Institute; Robert Wood Johnson Foundation; Medtronic; Johnson & Johnson; Chinese National Center for Cardiovascular Disease; Centers for Medicare & Medicaid Services Editorial boards BMJ.com/US; American Journal of Managed Care; American Journal of Medicine; Archives of Medical Science; Critical Pathways in Cardiology; Current Cardiovascular Risk Reports; JACC: Cardiovascular Imaging; Circulation: Cardiovascular Quality and Outcomes; Circulation (Associate Editor)

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