Home > Uncategorized > Semaglutide and Cardiovascular Events (SUSTAIN-6)

Semaglutide and Cardiovascular Events (SUSTAIN-6)


Marso et al
report the cardiovascular safety data of the glucagon-like peptide (GLP-1) analogue in patients with type II diabetes mellitus (weekly injection 0.5 or 1 mg). A non-inferiority margin of  1.8 ( hazard ratio) for the 95% upper bound of the hazard ratio. Semaglutide was associated with lower rates of cardiovascular death and non-fatal myocardial infarction (approximately 2 years follow up). The hazard ratio was below the inferiority margin.

Abstract

BACKGROUND

Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown.

METHODS

We randomly assigned 3297 patients with type 2 diabetes who were on a standard care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. We hypothesized that semaglutide would be noninferior to placebo for the primary outcome. The noninferiority margin was 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio.

RESULTS

At baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both. The primary outcome occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.58 to 0.95; P<0.001 for noninferiority).
Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74; 95% CI, 0.51 to 1.08; P = 0.12); nonfatal stroke occurred in 1.6% and 2.7%, respectively (hazard ratio, 0.61; 95% CI, 0.38 to 0.99; P = 0.04). Rates of death from cardiovascular causes weresimilar in the two groups. Rates of new or worsening nephropathy were lower in the semaglutide group, but rates of retinopathy complications (vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation)
were significantly higher (hazard ratio, 1.76; 95% CI, 1.11 to 2.78; P = 0.02). Fewer serious adverse events occurred in the semaglutide group, although more patients discontinued treatment because of adverse events, mainly gastrointestinal.

CONCLUSIONS

In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide.

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