Introduction: Weight loss is the cornerstone of treatment for type 2 diabetes, but may be difficult to achieve with diet and exercise alone. This study was designed to evaluate the safety and efficacy of lorcaserin (Belviq) for weight loss in patients with type 2 diabetes. The effect of lorcaserin on glycemic control also was evaluated.
Methods: The 1-year, randomized, double-blind, placebo-controlled trial evaluated 604 obese and overweight patients (body mass index 27-45 kg/m2) with type 2 diabetes. Patients were randomized to lorcaserin 10 mg once daily (n=95), lorcaserin 10 mg twice daily (n=256), or placebo (n=253) for 1 year as well as diet and exercise counseling. The patients were treated with metformin, a sulfonylurea, or both, and had HbA1c at screening visit of 7% to 10%.
Results: At 52 weeks, a significantly greater percentage of patients in the lorcaserin 10 mg once-daily and twice-daily groups achieved at least 5% weight loss compared with the placebo group (44.7%, 37.5%, and 16.1%, respectively; P<0.001). Mean weight change also was significantly greater in the lorcaserin groups than in the placebo group (-5.0%, -4.5%, and -1.5%; P<0.001). In addition, the lorcaserin groups experienced a significantly greater decrease in hemoglobin A1c (-1.0, -0.9, and -0.4 respectively; P<0.001) and fasting glucose level (-28.4, -27.4, and -11.9 mg/dL, respectively; P<0.001). Furthermore, the lorcaserin groups showed a significantly greater decrease in heart rate compared with the placebo group (P=0.03 and P=0.01). The most common side effects reported in the lorcaserin groups were headache, upper respiratory infection, back pain, and nasopharyngitis.
Conclusion: Lorcaserin was associated with significant weight loss and improved glycemic control in overweight and obese patients with type 2 diabetes.
Commentary by Louis Kuritzky MD
Most patients with type 2 diabetes mellitus (T2DM) are overweight or obese. Some of the most highly efficacious agents to control glucose (insulin, sulfonylurea) tend to increase body weight despite improvements in glucose control. Weight loss is particularly beneficial for T2DM patients because it is associated with better glycemic control, improved insulin sensitivity, reduced blood pressure, and improvements in dyslipidemia.
The BLOOM-DM (Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus) study provides a hopeful signal for T2DM patients who are unable to attain more desirable body weight using lifestyle measures alone, or who are not surgical candidates.1
Lorcaserin is the first FDA-approved member of a new class of agents, selective serotonin 2C (5-HT2C) receptor agonists. Previous pharmacotherapeutic experience with dexfenfluramine (Redux) as part of the so-called “Fen-Phen” regimen was curtailed due to recognition that the 5-HT2B (NOT 5-HT2C) was associated with valvulopathy and pulmonary hypertension. Clinical trials of lorcaserin have included echocardiographic evaluation to confirm that 5-HT2C has no negative cardiovascular impact.
The BLOOM-DM trial randomized overweight or obese T2DM adults (n=604) to lorcaserin 10 to 20 mg/d or placebo for 1 year. Prespecified outcomes included: mean weight loss, percent of individuals losing at least 5% and at least 10% of body weight, A1c, fasting glucose, fasting insulin, lipids, blood pressure, waist circumference, and quality of life.
At the end of 1 year, in the treatment groups (10 mg/d and 10 mg bid) there were statistically significantly effects compared to placebo for at least 5% weight loss (44.7% and 37.5% vs 16.1%) and A1c (1.0 and 0.9 decline vs 0.4 decline). Lorcaserin was generally well tolerated with a discontinuation rate due to adverse effects slightly less than placebo (4.6% vs 5.3%). Echocardiographic studies did not demonstrate any cardiovascular toxicity. Lorcaserin may be a valuable adjunct for weight loss in T2DM patients.