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SUSTAIN-6: Retinopathy complications may be increased with semaglutide
SAN DIEGO — An analysis of data from SUSTAIN-6, the cardiovascular outcome trial of the glucagon-like peptide 1 receptor agonist semaglutide, sheds light on the increased rate of diabetic retinopathy complications found in the treatment groups compared with the placebo groups, according to a speaker here.
In the SUSTAIN-6 CV outcome trial, Tina Vilsbøll, MD, DMSc, clinical manager at Steno Diabetes Center in Copenhagen, Denmark, and colleagues randomly assigned 3,297 adults with type 2 diabetes (median age, 64.6 years; 60.7% men; 2,735 with established CVD, kidney disease or both) to receive either 0.5-mg or 1-mg semaglutide (Novo Nordisk), or placebo weekly, in addition to their standard-care regimen. Primary outcome was the composite of first event of CV death, nonfatal myocardial infarction or nonfatal stroke. Retinopathy was a prespecified secondary outcome.
Fewer participants in the semaglutide group compared with the placebo group experienced the composite primary outcome: 6.6% vs. 8.9%, respectively (P < .001 for noninferiority). The semaglutide group also had lower rates of new or worsening nephropathy compared with the placebo group, whereas retinopathy complication rates were significantly higher in the semaglutide group, occurring in 50 (3%) vs. 29 (1.8%) patients (HR = 1.76; 95% CI, 1.11-2.78; P = 0.02).
Complications included the need for retinal photocoagulation in 38 patients (2.3%) in the semaglutide group vs. 20 (1.2%) in the placebo group and for intravitreal agent injections in 16 (1%) vs. 13 (0.8%) patients in the semaglutide vs. placebo groups. Vitreous hemorrhage occurred in 16 (1%) vs. 7 (0.4%) patients, respectively, and diabetes-related blindness
in 5 (0.3%) patients in the semaglutide groups vs. 1 (0.1%) in the placebo groups.
“In absolute numbers, the numbers were low. ... [There were] 50 and 29 events in total and distributed under the four different events,” Vilsbøll said. “What you can see is in relation to all events, [the rate] was higher with semaglutide. It was not just one of the four, but numerically all four were higher in the semaglutide-treated patients.
“Then we did some further analyses to learn more about the patients who had these complications,” she said.
The 79 participants who experienced a retinopathy complication had a longer duration of diabetes and higher mean HbA1c, 9.4% for the retinopathy group vs. 8.7% in the cohort overall. Nearly 65% of the retinopathy group was taking insulin vs. 58% of the overall population. Among the complications group, at baseline 83.5% had a history of diabetic retinopathy. A history of proliferative retinopathy was present in 29% of the complications group vs. 6.1% of the participants overall, and a history of laser or injection treatment for proliferative retinopathy was present in 17.7% vs. 3.4%, respectively.
“When we split the patients into patients without retinopathy at baseline and patients with retinopathy, patients who did not have any history of retinopathy [had] no signals with semaglutide — it was exactly the same as placebo,” Vilsbøll said.
Also, patients who had retinopathy complications had a rapid and steep decrease of approximately 2.5% in HbA1c level, and rapid improvement in glycemic control is a risk factor for retinopathy complications, Vilsbøll said.
“Summarizing this: When initiating a highly effective treatment as semaglutide [is], similar guidance should be given in these vulnerable patients,” she said. – by Jill Rollet
Reference:
Marso ST, et al. N Engl J Med. 2016;doi:10.1056/NEJMMoa1607141.
Vilsbøll T. Cardiovascular Outcomes with Semaglutide in Subjects with Type 2 diabetes Mellitus (SUSTAIN 6). Presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017; San Diego.
Disclosures: Vilsbøll reports serving on the advisory panel and as a speaker for Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk A/S, and Sanofi.