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.


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; 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)


Your Comment

(will not be published)

Filtered HTML

  • Allowed HTML tags: <a> <em> <strong> <cite> <blockquote> <code> <ul> <ol> <li> <dl> <dt> <dd>
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Do you have any conflict of interest to disclose?
This question is for testing whether you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

* Required

Reader comments are intended to encourage lively discussion of clinical topics with your peers in the medical community. We ask that you keep your remarks to a reasonable length, and we reserve the right to withhold publication of remarks that do not meet this standard.

PRIVACY: We will not use your email address, submitted for a comment, for any other purpose nor sell, rent, or share your e-mail address with any third parties. Please see our Privacy Policy.