New research presented at this year’s annual meeting of the European Association for the Study of Diabetes (EASD) in Berlin, Germany, and published in The Lancet, shows that the appetite-suppressant drug lorcaserin decreases risk of developing diabetes and increases the rates of remission of high blood sugar. Lorcaserin also reduces the risk of kidney complications due to diabetes in obese and overweight patients. The study is by Dr Erin Bohula and Dr Benjamin Scirica and colleagues from the Brigham and Women’s Hospital investigators from the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Boston, MA, and Harvard University, Cambridge, MA, USA.
There is a direct relationship between increased body weight and the risk of diabetes. In CAMELLIA-TIMI 61, lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite has been shown to facilitate sustained weight loss in obese or overweight patients. As reported last month, lorcaserin facilitated modest but sustained weight loss without an increased risk of major adverse cardiovascular events in obese or overweight patients at high cardiovascular risk. The long-term effects of lorcaserin on diabetes prevention and remission, however, are unknown.
CAMELLIA-TIMI 61 was a randomized, double-blind, multi-national trial of lorcaserin or placebo on a background of lifestyle modification in overweight or obese patients with or at high risk for atherosclerotic vascular disease. The prespecified endpoint of incident diabetes was assessed in patients with prediabetes at baseline. Other prespecified outcomes for efficacy included remission of hyperglycemia (high blood sugar), achievement of blood sugar in the normal range, reducing diabetic microvascular complications, and for safety, hypoglycemia (incidents of dangerously low blood sugar).
A total 12,000 patients were randomized from February 2014 through to November 2015 and followed for a median of 3.3 years. At 1 year, patients with baseline diabetes (N=6816, 57%), pre-diabetes (N=3991, 33%) and normoglycemia (N=1193, 10%) treated with lorcaserin had a 2.6 kg, 2.8 kg, and 3.3 kg net weight loss, respectively, with all results statistically significant.
Lorcaserin reduced the risk of incident diabetes by 19% in patients with prediabetes (8.5% vs 10.3%). Furthermore, lorcaserin tended to increase the rate of achievement of normoglycemia in patients with prediabetes (9.2% vs. 7.6%, although not statistically significant) and significantly increased the rate of remission of hyperglycemia in patients with diabetes by 21% (7.1% vs. 6.0%). Lorcaserin also reduced the risk of a composite of microvascular events of incident microalbuminuria, diabetic retinopathy or neuropathy by 21% in patients with diabetes (10.1% vs. 12.4%). In patients with diabetes at baseline, severe hypoglycemia with serious complications was rare, but more common with lorcaserin (12 vs 4 events, borderline statistical significance). In patients with diabetes, lorcaserin reduced glycated hemoglobin (HbA1c by 0.3% compared with placebo at 1 year from a mean baseline of 7.0%.
The authors say: “Lorcaserin is effective for weight loss, and in contrast to many other obesity medications to date, has proven safety for major adverse cardiovascular events, including CV death, myocardial infarction or stroke.”
They add: “Now, in addition to proven persistent weight loss efficacy with extended duration use, we report that when added to lifestyle interventions, lorcaserin significantly reduced the incidence of diabetes, tended to increase achievement of normoglycemia in patients with prediabetes, increased the rate of remission of hyperglycemia in patients with diabetes, and reduced the risk of diabetic microvascular complications. Taken together, these findings reinforce the notion that modest, durable weight loss can improve cardiometabolic health and supports the role of lorcaserin as an adjunctive therapy in chronic weight management and metabolic health.”
They conclude: “Lorcaserin is approved in the United States, but not in most European counties. We feel that the results from CAMELLIA-TIMI 61 provide clinicians, patients, and regulatory officials with extensive data from a large, well-characterized patient population at high risk for cardiovascular events, so they can make the most informed decisions as possible regarding efficacy and safety.”