BERLIN – Lower rates of incident type 2 diabetes mellitus (T2DM) and improved glycemic control were two of the metabolic effects seen with the appetite-suppressant drug lorcaserin versus placebo on top of existing lifestyle management measures in a large-scale trial of more than 12,000 overweight or obese individuals with established cardiovascular disease or T2DM and other cardiovascular risk factors.Lorcaserin HCL

In the CAMELLIA-TIMI 61 trial, treatment with a twice-daily, 10-mg dose of lorcaserin for a median of 3.3 years was associated with a significant 19% reduction in the risk of incident T2DM in participants with prediabetes, compared with placebo (8.5% vs. 10.3%; hazard ratio, 0.81; 95% confidence interval, 0.66-0.99; P = .038). The reduction in the risk of incident T2DM was even greater (23%) in people without diabetes at baseline (6.7% lorcaserin vs. 8.4% placebo; HR, 0.77; 95% CI, 0.63-0.94; P = .012).

Furthermore, in patients with T2DM who had a mean baseline glycated hemoglobin (HbA1c) of 7%, an absolute 0.33% reduction was seen at 1 year between the lorcaserin and placebo groups, with more modest but still significant between-group reductions (–0.09% and –0.08%) in individuals with prediabetes or normoglycemia (all P less than .0001). When baseline HbA1c levels were higher in patients with T2DM (8%), greater net reductions (0.52%) versus placebo were seen (P less than .0001).

These were some of the metabolic findings, published online in the Lancet to coincide with their presentation at the annual meeting of the European Association for the Study of Diabetes, that add to those already released from the CAMELLIA-TIMI 61 trial on cardiovascular safety, lead author and TIMI (Thrombolysis in Myocardial Infarction) group investigator Erin A. Bohula May, MD, observed during a press conference.

The cardiovascular safety data were presented at the 2018 annual congress of the European Society for Cardiology in August and published in the New England Journal of Medicine. These showed no increase with lorcaserin versus placebo in the risk of achieving a major cardiovascular endpoint (MACE) of cardiovascular death, MI, or stroke (HR, 0.99; 95% CI, 0.85-1.14; P less than .001 for noninferiority). There was also no difference between groups in the cumulative incidence of MACE+, which included heart failure, hospitalization for unstable angina, and the need for coronary revascularization (HR, 0.97; 95% CI, 0.87-1.07; P = .55 for superiority).

“We know that weight loss can improve cardiovascular and glycemic risk factors, but it’s difficult to achieve and maintain, and weight-loss agents are guideline-recommended adjuncts to lifestyle modification,” said Dr. Bohula May, who is a cardiovascular medicine and critical care specialist at Brigham and Women’s Hospital in Boston.

“However, prior to this study no agent had convincingly demonstrated cardiovascular safety in a rigorous clinical outcomes study,” she said, noting that several agents, such as the now-withdrawn rimonabant (Acomplia/Zimulti) and sibutramine (Meridia), had been shown to precipitate cardiovascular or psychiatric events, which led the Food and Drug Administration to mandate that all weight-loss drugs be assessed for cardiovascular safety. Lorcaserin (Belviq) is a centrally acting 5-HT2C agonist that works by decreasing appetite and was approved by the FDA in 2012 but is not currently available in Europe.

Long-term data on the effects of weight-loss agents on glycemic parameters were limited, hence the remit of the CAMELLIA-TIMI 61 trial was to assess both the cardiovascular and metabolic safety of lorcaserin. The drug was used on a background of lifestyle modification in 6,000 obese or overweight individuals at high risk of cardiovascular events. A further 6,000 individuals received placebo.