Appetite suppressant lorcaserin may prevent incident diabetes in obese, overweight patients
Overweight or obese patients taking lorcaserin as an appetite suppressant may have the added benefit of a reduced risk of incident diabetes, according to results of the CAMELLIA-TIMI 61* trial presented at EASD 2018.
“On the background of lifestyle modification, lorcaserin resulted in modest, but durable, weight loss in overweight and obese patients with and without diabetes and to overall improvements in glycaemic control,” said the study authors.
In addition to undergoing a lifestyle modification-based weight management programme, 12,000 overweight or obese individuals (BMI ≥27 kg/m2; median age 64 years, 35.8 percent female, median baseline BMI 35 kg/m2) with atherosclerotic cardiovascular disease (CVD) or multiple CV risk factors were recruited from 473 sites in eight countries and randomized 1:1 to receive either the selective serotonin 2C receptor agonist (5-HT2C) lorcaserin (10 mg BID) or placebo. Patients were followed up for a median 3.3 years. More than half of the patients (56.8 percent) had diabetes at baseline, while 33.3 and 9.9 percent had pre-diabetes and normoglycaemia, respectively. The use of diabetes treatment medications was permitted.
At 1 year, net weight loss with lorcaserin was higher than that with placebo (least-squares [LS] mean treatment difference, -2.6, -2.8, and -3.3 kg for patients with diabetes, prediabetes, and normoglycaemia, respectively; p<0.0001 for all).
There was a 19 percent decrease in the risk of incident diabetes among patients with prediabetes at baseline (HbA1c ≥5.7 to <6.5 percent or fasting plasma glucose 5.6–6.9 mmol/L) who received lorcaserin compared with those who received placebo (8.5 percent vs 10.3 percent, hazard ratio [HR], 0.81, 95 percent confidence interval [CI], 0.66–0.99; p=0.038). Among all patients without diabetes at baseline, the risk of incident diabetes reduced by 23 percent (6.7 percent vs 8.4 percent, HR, 0.77, 95 percent CI, 0.63–0.94; p=0.012). [EASD 2018, oral presentation S33.4; Lancet 2018;doi:10.1016/S0140-6736(18)32328-6]
At 1 year, patients with diabetes (mean baseline HbA1c 7.0 percent) who received lorcaserin experienced a significant decrease (0.33 percent) in HbA1c levels compared with those on placebo (p<0.0001), as did those with prediabetes and normoglycaemia (LS mean treatment difference, -0.09 and -0.08 percent, respectively; p<0.0001 for both).
Prediabetic lorcaserin recipients were also more likely to achieve normoglycaemia (without any glucose-lowering medications) than placebo recipients though the findings were not significant (9.2 percent vs 7.6 percent, HR, 1.20; p=0.093), while diabetic lorcaserin recipients were more likely to achieve remission of hyperglycaemia (7.1 percent vs 6.0 percent, HR, 1.21; p=0.049).
Patients with diabetes who received lorcaserin were less likely to initiate new glucose-lowering medications (p<0.0001) and more likely to discontinue glucose-lowering medications (p=0.0045) compared with those on placebo at 1 year. They also experienced fewer microvascular complications compared with placebo recipients (10.1 percent vs 12.4 percent, HR, 0.79; p=0.001), driven primarily by a lower incidence of persistent microalbuminuria (7.8 percent vs 10.0 percent; p=0.001).
The incidence of severe hypoglycaemia with serious complications was low in both lorcaserin and placebo recipients with diabetes, though slightly higher in the lorcaserin group (0.4 percent vs 0.1 percent; p=0.054).
“Taken together, these findings reinforce the notion that modest, durable weight loss can improve cardiometabolic health and supports the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health,” said study author Associate Professor Benjamin Scirica from the Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, US.
Though the positive impact on glucose control with lorcaserin is assumed to be “weight dependent”, mechanisms behind the effect are undetermined, and potentially due to “decreased caloric intake” or “suppression of hepatic gluconeogenesis”, said the authors.