Diabetes drug lowers stroke risk, increases odds of retinopathy complications

By Gene Emery

NEW YORK (Reuters Health) - Semaglutide, Novo Nordisk's experimental GLP-1 analogue treatment for diabetes, given subcutaneously once a week, cuts the composite risk of a first-time heart attack, stroke or cardiovascular death by 26%, according to published findings released Friday.

But when those outcomes were evaluated separately, semaglutide only produced a statistically significant reduction in nonfatal stroke. It did, however, increase the odds of retinopathic complications by 76%.

Gastrointestinal side effects were common.

The results of the international SUSTAIN-6 study were released Friday morning by the New England Journal of Medicine to coincide with the European Association for the Study of Diabetes annual meeting in Munich. Novo Nordisk, which funded the test, released a few details about the results in April, sending shares in the Danish drug maker up as much as 3.5 percent.

Of the 3,297 volunteers with type 2 diabetes, 83% had established cardiovascular disease, chronic kidney disease, or both. They were followed for two years.

While 8.9% of patients on placebo for 104 weeks developed one of the three composite outcomes, the rate was 6.6% with once-weekly treatment with semaglutide (P

The researchers estimated that 45 patients would need to be treated for 24 months to prevent one stroke, heart attack or cardiovascular death.

The odds of a nonfatal heart attack were lower with the drug - 2.9% versus 3.9% with placebo - but the difference was not statistically significant (P=0.12).

There was no difference in the risk of cardiovascular death (P=0.92) or death from any cause (P=0.79).

However, while 2.7% of placebo recipients had a nonfatal stroke, the rate was 1.6% with semaglutide, a reduction of 39% (P=0.04).

People on the drug also had lower rates of new or worsening nephropathy. The rate was 3.8% with the drug and 6.1% without (P=0.005).

Drug recipients were also significantly less likely to require a revascularization procedure. It was done in 5.0% of semaglutide recipients versus 7.6% of placebo patients (P=0.003).

The overall rates of serious or severe adverse events were similar whether patients received the drug or placebo.

However, when the researchers looked at a composite of retinopathy complications, such as blindness, vitreous hemorrhage, or conditions requiring treatment with photocoagulation or an intravitreal agent, they found rates of 3.0% with the drug and 1.8% with placebo, a 76% increase for people on semaglutide (P=0.02).

The researchers said that problem was unexpected.

The most common problems were gastrointestinal, affecting 51% of the low-dose (0.5 mg) patients and 36% of placebo patients. Diarrhea plagued 18%, nausea affected 17% and vomiting was reported by nearly 11%.

Ultimately, 11.5% of the volunteers in the low dose semaglutide group discontinued their treatment because of adverse events. The discontinuation rate was 14.5% when the dose was twice as high - compared to only 5.7% with placebo.

SOURCE: https://bit.ly/2ciRhq5

N Engl J Med 2016.