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. Funding: Eisai.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2269-2279 |
| Number of pages | 11 |
| Journal | The Lancet |
| Volume | 392 |
| Issue number | 10161 |
| DOIs | |
| State | Published - Nov 24 2018 |
Funding
EAB reports grants from Eisai, during the conduct of the study; and personal fees from Servier, Merck, National Institutes OF Health, Lexicon, Medscape, Academic CME, MD Conference Express, Paradigm, and Novartis and grants from Amgen, AstraZeneca, and Merck, outside of the submitted work. MPB reports grants from BWH/TIMI Study Group, during the conduct of the study; and grants and other support from Amgen, Aralez, and AstraZeneca; other support from Bayer and Janssen; grants from MedImmune and Pfizer; grants, personal fees, and other support from Merck; and other support from Sanofi, outside of the submitted work. RC and JPD report personal fees from Eisai, during the conduct of the study. SEI reports personal fees from Eisai, during the conduct of the study; and personal fees from Merck, Janssen, AstraZeneca, Novo Nordisk, Sanofi/Lexicon, Intarcia, Daiichi Sankyo, Alere, and VTV Therapeutics; and personal fees and non-financial support from Boehringer Ingelheim, outside of the submitted work. EK reports grants from Abbott Laboratories, Amgen, AstraZeneca, Critical Diagnostics, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Merck, Roche Diagnostics, Takeda, Gilead, Poxel, Novartis, MedImmune, Janssen Research Development, and Genzyme, outside of the submitted work. ACK reports other support from Eisai, during the conduct of the study; and grants and personal fees from Abbott and Mylan; personal fees from Amgen, Pfizer, Bayer, and AstraZeneca; and grants from Sanofi and Novartis, outside of the submitted work. LAL reports personal fees from Eisai, during the conduct of the study; and grants and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, and Sanofi; personal fees from Servier; and grants from GlaxoSmithKline, outside of the submitted work. DKM reports personal fees from Eisai, during the conduct of the study; and personal fees from Boehringer Ingelheim, Janssen Research and Development, Sanofi US, Merck Sharp & Dohme, Eli Lilly, Novo Nordisk, GlaxoSmithKline, AstraZeneca, Lexicon, Eisai, Esperion, Metavant, and Pfizer, outside of the submitted work. SAM reports grants from Abbott Laboratories, Amgen, AstraZeneca, Critical Diagnostics, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Roche Diagnostics, Takeda, Gilead, Poxel, Novartis, MedImmune, Janssen Research Development, and Genzyme; and grants and honorarium from Merck, outside of the submitted work. JCN reports personal fees from Amgen and Servier; grants from AstraZeneca, Bayer, BMS, CLS Behring, Novartis, and Dalcor; and grants and personal fees from Sanofi, Vifor, and Pfizer, outside of the submitted work. TP, WM, and CP report employment for Eisai. KKR reports personal fees from AbbVie; grants and personal fees from Amgen, Sanofi, Regeron, Merck Sharp & Dohme, Pfizer, AstraZeneca, MedCo, Resverlogix, Akcea, Boehringer Ingelheim, Novo Nordisk, Takeda, Kowa, Cerenis, Cipla, Algorithm, and Esperion, outside of the submitted work. CTR reports grants from Eisai, during the conduct of the study; and grants and personal fees from Boehringer-Ingelheim, Bayer, Janssen, Portola, and Daiichi Sankyo, outside of the submitted work. MSS reports grants from Eisai, during the conduct of the study; and grants and personal fees from Amgen, Intarcia, Janssen, Medicines Company, Medimmune, Merck, Novartis, AstraZeneca, Intarcia, Janssen Research and Development, Medicines Company, Medimmune, Merck, and Novartis; grants from Daiichi-Sankyo, Eisai, GlaxoSmithKline, Pfizer, Poxel, Takeda, Abbott Laboratories, Critical Diagnostics, Genzyme, Gilead, and Roche Diagnostics; and personal fees from Bristol-Myers Squibb, CVS Caremark, Dyrnamix, Esperion, Alnylam, Ionis, and MyoKardia, outside of the submitted work. BMS reports grants from Eisai, during the conduct of the study; and grants from AstraZenaca, Novartis, and Merck; personal fees from AstraZeneca, Biogen Idec, Boehringer Ingelheim, Covance, Dr Reddy's Laboratory, Eisai, Elsevier Practice Update Cardiology, GlaxoSmithKline, Merck, NovoNordisk, Sanofi, and St Jude's Medical; and other support from Health [at] Scale, outside of the submitted work. SRS reports personal fees from Eisai, outside of the submitted work. SDW reports grants from Eisai, during the conduct of the study; and grants from Amgen and Sanofi-Aventis; grants and personal fees from Arena, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly, and Janssen; grants, personal fees, and other support from Merck; and personal fees from Aegerion, Allergan, Angelmed, Boehringer Ingelheim, Boston Clinical Research Institute, Icon Clinical, Lexicon, St Jude Medical, and Xoma, outside of the submitted work. All remaining authors declare no competing interests.
ASJC Scopus subject areas
- General Medicine
