Journal Article

Effect of lorcaserin on prevention and remission of type 2 diabetes in overweight and obese patients (CAMELLIA-TIMI 61): a randomised, placebo-controlled trial

Dwyer, Jamie, Bialow, M, Llamas Esperon, G, Amerena, J, Bhagwat, R, Nirmalaraj, BK, Trueba, P, Cobos, J, Weinstein, D, Schramm, E, Salacata, A, Paraschos, A, Perez, A, Kroll, R, Nelson, W, Henson, B, Perez, L, Harper, W, Studdard, H, Goch, A, Shepard, M, Garcia-Castillo, Armando, Fialkow, J, Fortin, C, Murphy, Sabina A, Garza Ruiz, J, Cannon, K, Kahn, B, Piepiorka, M, Rodbard, H, Keech, Anthony, Laskowska-Derlaga, E, Neustel, M, Colquhoun, D, Bonaca, Marc P, Sharma, S, Cheung, D, Skórski, M, French, W, Hoekstra, J, Ternouth, I, Inzucchi, Silvio E, Aycock, GR, Benson, M, Huffman, C, Rider, J, Atieh, M, Hong, M, Hess, A, Mahal, S, Saeed, S, Essandoh, L, White, J, Kalen, V, Rogers, W, Alfonso, T, White, A, Selvanayagam, J, Tallet, J, Hershon, K, Pincetti, C, Godoy, G, Liu, J, Miękus, P, Labroo, A, Wahlen, J, Zhang, L, Sorli, C, Navas, J, Srivastava, S, Chane, M, Phillips, C, Pritchard, J, Lee, J, Chokshi, S, Kaplan, Lee, Hotchkiss, D, William, M, Worthley, M, Wilson, S, Tami, L, Lee, A, Pomposini, D, Browder, D, Bell, A, Gerrish, C, Dor, I, Yared, Z, Lubin, B, Jayasinghe, R, Sabatine, Marc S, Ellison, H, Pomiećko, W, Twum-Barima, D, Snyder, H, Wujkowski, M, Robinson, J, Odhav, A

2018

Overview

There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission. In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m2) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA1c) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264. Between Feb 7, 2014, and Nov 20, 2015, 12 000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3·3 years (IQR 3·0–3·5). At baseline, 6816 patients (56·8%) had diabetes, 3991 (33·3%) prediabetes, and 1193 (9·9%) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg (95% CI 2·3–2·9) for those with diabetes, 2·8 kg (2·5–3·2) for those with prediabetes, and 3·3 kg (2·6–4·0) for those with normoglycaemia (p<0·0001 for all analyses). Lorcaserin reduced the risk of incident diabetes by 19% in patients with prediabetes (172 [8·5%] of 2015 vs 204 [10·3%] of 1976; hazard ratio 0·81, 95% CI 0·66–0·99; p=0·038) and by 23% in patients without diabetes (174 [6·7%] of 2615 vs 215 [8·4%] of 2569; 0·77, 0·63–0·94; p=0·012). Lorcaserin resulted in a non-significant increase in the rate of achievement of normoglycaemia in patients with prediabetes (185 [9·2%] vs 151 [7·6%]; 1·20, 0·97–1·49; p=0·093). In patients with diabetes, lorcaserin resulted in a reduction of 0·33% (95% CI 0·29–0·38; p<0·0001) in HbA1c compared with placebo at 1 year from a mean baseline of 53 mmol/mol (7·0%). In patients with diabetes at baseline, severe hypoglycaemia with serious complications was rare, but more common with lorcaserin (12 [0·4%] vs four [0·1%] events; p=0·054). Lorcaserin decreases risk for incident diabetes, induces remission of hyperglycaemia, and reduces the risk of microvascular complications in obese and overweight patients, supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health. Eisai.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Aged / Appetite / Appetite Depressants - therapeutic use / Arteriosclerosis / Atherosclerosis / Atherosclerosis - complications / Atherosclerosis - drug therapy / Benzazepines - therapeutic use / Body mass index / Body weight / Body Weight - drug effects / Body weight loss / Cardiovascular disease / Coronary vessels / Diabetes / Diabetes mellitus / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - drug therapy / Diabetes Mellitus, Type 2 - prevention & control / Diabetic neuropathy / Diabetic retinopathy / Disease prevention / Double-Blind Method / Double-blind studies / Evidence-based medicine / FDA approval / Female / Gastrointestinal surgery / Glycated Hemoglobin A - analysis / Health risk assessment / Health risks / Heart attacks / Hemoglobin / Humans / Hyperglycemia / Hypertension / Hypoglycemia / Hypoglycemic Agents - therapeutic use / Lifestyles / Long-term effects / Male / Metabolism / Microvasculature / Middle Aged / Motivation / Obesity / Obesity - complications / Overweight / Overweight - complications / Patients / Prediabetic State - complications / Prediabetic State - drug therapy / Prediabetic State - prevention & control / Randomization / Remission / Remission Induction / Risk analysis / Risk factors / Serotonin / Statistical models / Vascular diseases / Weight control / Weight loss / Weight Loss - drug effects