Hot off the presses from the New England Journal of Medicine – an emerging type 2 diabetes medication called semaglutide has been shown to decrease cardiovascular events in a high risk population with type 2 diabetes.
The two year study, called the SUSTAIN-6 study and in which I was an investigator, enrolled 3,297 people from 20 countries around the world who had established cardiovascular disease, or at least one cardiovascular risk factor. They were randomized to receive either semaglutide 0.5mg, semaglutide 1.0mg, or placebo as once weekly subcutaneous injections.
The primary outcome of the study, which was a composite outcome of first occurrence of nonfatal heart attack, nonfatal stroke, or cardiovascular death, was found to be reduced by 26% compared to placebo, with 6.6% of patients on semaglutide experiencing an event, vs 8.9% of patients on placebo. When we look at these endpoints individually, there was a significant reduction of 39% of
nonfatal stroke, whereas the differences in nonfatal heart attack and death were not significant.
nonfatal stroke, whereas the differences in nonfatal heart attack and death were not significant.
Although all patients in the study were treated to achieve target glycemic control, blood glucose control was better in the semaglutide groups, with hemoglobin A1C reduced by 0.7% and 1.0% in the semaglutide 0.5mg and 1.0mg groups respectively, compared to placebo, despite the fact that insulin needed to be started twice as often in the placebo group than in the semaglutide group.
In terms of other complications that we are aiming to prevent in people with diabetes, rates of new or worsening kidney disease was reduced with semaglutide. The risk of retinopathic (eye) complications was higher, experienced by 3% of patients on semaglutide vs 1.8% of patients on placebo. Rarely, achieving glycemic control rapidly (particularly when sugars start off very high) can paradoxically increase the risk of eye complications. It is not clear if this was the reason in these patients; a direct effect of semaglutide cannot be ruled out.
So what does this mean for the care of people with type 2 diabetes? The above results suggest that 45 people with type 2 diabetes and high cardiovascular risk would need to be treated for 2 years in order to prevent one cardiovascular event. In the diabetes world, this is an impressive benefit, similar to the benefit of statins for cholesterol, and also in a similar realm to the two other diabetes medications, empagliflozin and liraglutide, that have been shown to prevent cardiovascular events (read more here and here). The data showing cardiovascular benefit on all three of these medications has come out within the last year – before that, we did not have definitive evidence that any diabetes medication clearly reduces the risk of cardiovascular events.
It is indeed wonderful that we now know that some glucose lowering medications are able to prevent cardiovascular events in people with type 2 diabetes. While semaglutide has not yet been approved for use, this study suggests that it will be a beneficial addition to our type 2 diabetes treatment armamentarium.
Disclaimer: I have been involved in research trials of semaglutide, other GLP-1 receptor agonists including liraglutide, and SGLT2 inhibitors like empagliflozin. I receive honoraria as a continuing medical education speaker and consultant from the makers of semaglutide and liraglutide (Novo Nordisk) and empagliflozin (Boehringer-Ingelheim/Eli Lilly).
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