SUSTAIN-6 was a double-blind, randomised controlled trial in which adults with type 2 diabetes and high CV risk (either established CV disease or one or more CV risk factor alongside stage ≥3 chronic kidney disease or age ≥60 years) were enrolled. These participants (n=3297) were randomised 1:1:1:1 to semaglutide 0.5 mg, 1.0 mg or the same volumes of placebo, all in conjunction with standard of care.
After 2 years of treatment, the primary outcome – the first occurrence of death from CV causes, non-fatal myocardial infarction or non-fatal stroke – had occurred in 6.6% of semaglutide recipients versus 8.9% of placebo recipients (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.58–0.95; P<0.001 for non-inferiority; P=0.02 for superiority). This was mainly driven by a significant (39%) reduction in the rate of non-fatal stroke and a non-significant (26%) reduction in non-fatal myocardial infarction, with no significant difference in the rate of CV death. The number needed to treat to prevent one event of the primary outcome over 2 years was estimated to be 45.
Mean HbA1c reduced significantly with both semaglutide doses compared to placebo, with a treatment difference of 7 mmol/mol (0.7%) and 11 mmol/mol (1.0%) with the 0.5 mg and 1.0 mg doses, respectively. Reductions in body weight (treatment differences of 2.9 kg and 4.3 kg) and systolic blood pressure (3.4 mmHg and 5.4 mmHg) were also significantly greater with semaglutide for the two doses.
New or worsening nephropathy was significantly less common in semaglutide recipients (3.8% vs 6.1%; HR, 0.64; 95% CI, 0.46–0.88). However, interestingly, complications due to diabetic retinopathy were more common (3.0% vs 1.8%; HR, 1.76; 95% CI, 1.11–2.78). The authors note a previously observed association between rapid glucose lowering and worsening of retinopathy in people with type 1 diabetes and suggest that neither this nor a direct effect of semaglutide can be ruled out.
The most common adverse events observed with the 0.5 mg and 1.0 mg doses were nausea (11.4% and 16.8%, respectively, vs 4.5% with placebo) and severe or blood glucose-confirmed symptomatic hypoglycaemia (8.3% and 10.7% vs 5.3%).
The results, published simultaneously in the New England Journal of Medicine, can be read in full here.
