Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

The SUSTAIN-6 trial was a randomized, double-blind, placebo-controlled study designed to evaluate the cardiovascular safety of semaglutide in patients with type 2 diabetes and high cardiovascular risk. The study included 3,297 patients who received subcutaneous semaglutide (0.5 or 1.0 mg weekly) or matching placebo during a median follow-up of 2.1 years.

The primary composite endpoint (MACE — major adverse cardiovascular events) included cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The results were notable: semaglutide reduced MACE by 26% compared to placebo (HR 0.74; 95% CI 0.58-0.95; p<0.001 for non-inferiority).

Analyses of individual components revealed:

• 39% reduction in non-fatal strokes (HR 0.61)
• Trend toward reduction in non-fatal myocardial infarctions (HR 0.74)
• No significant difference in cardiovascular death (HR 0.98)
• Significant reduction in the need for revascularization and in nephropathy rates

Interestingly, there was an increase in diabetic retinopathy rates in the semaglutide group, likely related to rapid glycemic improvement. HbA1c was reduced by 1.0-1.4 percentage points and body weight decreased 2.9-4.3 kg more than placebo.

SUSTAIN-6 was a landmark because it transformed semaglutide from a simple antidiabetic into a drug with proven cardiovascular benefit, significantly influencing type 2 diabetes treatment guidelines and paving the way for the SELECT trial in patients with obesity without diabetes.