Lancet:氯卡色林可预防或缓解超重/肥胖患者的2型糖尿病

创作:沈志勋 审核:沈志勋 10月14日
纳入12000名BMI≥27并有着高动脉粥样硬化风险的超重/肥胖患者,平均分为2组,分别使用氯卡色林或安慰剂治疗,随访3.3年(中位数);
相比于安慰剂组,氯卡色林组的糖尿病/前驱糖尿病/血糖正常患者的体重分别减少了2.6kg、2.8kg、3.3kg;
在前驱糖尿病及血糖正常患者中,氯卡色林分别显著降低了19%及23%的糖尿病风险;
在糖尿病患者中,氯卡色林显著降低了0.33%的HbA1c水平,但略微升高了低血糖的风险(差异不显著)。
延伸阅读
Lancet [IF:53.254]

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

氯卡色林对超重/肥胖患者的2型糖尿病的预防及缓解作用:一项随机安慰剂对照临床试验

10-04, Article, 10.1016/S0140-6736(18)32328-6more

Abstract:
Background: 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.
Methods: 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.
Findings: 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).
Interpretation: 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.

First Authors:
Marc S Sabatine,Stephen D Wiviott

Correspondence Authors:
Erin A Bohula,Benjamin M Scirica

All Authors:
Erin A Bohula,Benjamin M Scirica,Silvio E Inzucchi,Darren K McGuire,Anthony C Keech,Steven R Smith,Estella Kanevsky,Sabina A Murphy,Lawrence A Leiter,Jamie P Dwyer,Ramon Corbalan,Christian Hamm,Lee Kaplan,Jose Carlos Nicolau,Ton Oude Ophuis,Kausik K Ray,Mikhail Ruda,Jindrich Spinar,Tushar Patel,Wenfeng Miao,Carlos Perdomo,Bruce Francis,Shobha Dhadda,Marc P Bonaca,Christian T Ruff,Marc S Sabatine,Stephen D Wiviott