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.

• MeSH
• anorektika terapeutické užití   MeSH
• ateroskleróza komplikace   farmakoterapie   MeSH
• benzazepiny terapeutické užití   MeSH
• diabetes mellitus 2. typu krev   komplikace   farmakoterapie   prevence a kontrola   MeSH
• dvojitá slepá metoda MeSH
• glykovaný hemoglobin analýza   MeSH
• hmotnostní úbytek účinky léků   MeSH
• hypoglykemika terapeutické užití   MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• nadváha komplikace   MeSH
• obezita komplikace   MeSH
• prediabetes komplikace   farmakoterapie   prevence a kontrola   MeSH
• senioři MeSH
• tělesná hmotnost účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• anorektika MeSH
• benzazepiny MeSH
• glykovaný hemoglobin MeSH
• hypoglykemika MeSH
• lorcaserin MeSH Prohlížeč

A short overview of new drugs approved for the treatment of obesity (lorcaserin, phentermine/topiramate combination) as well as those with a perspective for approval as antiobesity drugs (cetilistat, naltrexone/bupropion combination, liraglutide) is presented. All these drugs produce significant weight loss accompanied by reductions in cardiometabolic health risks. Although the adverse events were rather rare and tended to decrease with the duration of treatment with most of these medications, the drug-specific safety concerns should be seriously considered. In order to ensure an appropriate, efficient and safe implementation of novel antiobesity drugs into the comprehensive treatment of obesity, it will be necessary to establish a network of physicians and other health-care providers well educated in obesity management.

• Klíčová slova
• antiobesity drugs, cetilistat, liraglutide, lorcaserin, naltrexone/bupropion, phentermine/topiramate,
• MeSH
• benzazepiny terapeutické užití   MeSH
• benzoxaziny terapeutické užití   MeSH
• bupropion terapeutické užití   MeSH
• fentermin terapeutické užití   MeSH
• fixní kombinace léků MeSH
• fruktosa analogy a deriváty   terapeutické užití   MeSH
• glukagonu podobný peptid 1 analogy a deriváty   terapeutické užití   MeSH
• hmotnostní úbytek účinky léků   MeSH
• látky proti obezitě terapeutické užití   MeSH
• lidé MeSH
• liraglutid MeSH
• naltrexon terapeutické užití   MeSH
• obezita farmakoterapie   MeSH
• topiramat MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH
• úvodníky MeSH
• Názvy látek
• benzazepiny MeSH
• benzoxaziny MeSH
• bupropion MeSH
• cetilistat MeSH Prohlížeč
• fentermin MeSH
• fixní kombinace léků MeSH
• fruktosa MeSH
• glukagonu podobný peptid 1 MeSH
• látky proti obezitě MeSH
• liraglutid MeSH
• lorcaserin MeSH Prohlížeč
• naltrexon MeSH
• topiramat MeSH

Worldwide obesity prevalence has nearly doubled since 1980. Due to numerous co-morbidities, obesity represents a serious health and socioeconomic problem worldwide. Pharmacotherapy should be an integral part of comprehensive obesity management. Drug therapy can assist in weight loss and its maintenance in those individuals who do not achieve appropriate weight loss through lifestyle interventions alone. After the withdrawal of sibutramine from the market in 2010, orlistat, a lipase inhibitor, was the only remaining prescription drug approved for the long-term treatment of obesity. In 2012, phentermine/topiramate extended-release (PHEN/TPM ER) combination and lorcaserin were approved by the US FDA as novel medications for long-term weight management. Three major phase III trials conducted with each drug confirmed their efficacy in terms of weight loss/maintenance and improvement of cardiometabolic risks. No head-to-head studies between the two new anti-obesity drugs have been carried out. However, in the existing studies PHEN/TPM ER had a superior weight loss profile to lorcaserin but the incidence of adverse effects was lower with lorcaserin. Both drugs were well-tolerated, and adverse events were modest in intensity, dose dependent, rather rare, and tended to decrease with the duration of treatment. Major safety concerns regarding PHEN/TPM ER include elevations in resting pulse rate, teratogenicity, mild metabolic acidosis, and psychiatric and cognitive adverse events. Valvulopathy, cognitive impairment, psychiatric disorders, and hypoglycemia represent major safety concerns for lorcaserin. Although existing trials have not demonstrated any significant issues with PHEN/TPM ER-induced heart rate elevation and lorcaserin-induced valvulopathy, all safety concerns should be seriously taken into account in patients treated with either of these novel anti-obesity medications.

• MeSH
• benzazepiny škodlivé účinky   MeSH
• benzoxaziny škodlivé účinky   MeSH
• bupropion škodlivé účinky   MeSH
• chemie farmaceutická MeSH
• fentermin aplikace a dávkování   škodlivé účinky   MeSH
• fruktosa aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• glukagonu podobný peptid 1 škodlivé účinky   analogy a deriváty   MeSH
• látky proti obezitě aplikace a dávkování   škodlivé účinky   MeSH
• lidé MeSH
• liraglutid MeSH
• naltrexon škodlivé účinky   MeSH
• nežádoucí účinky léčiv MeSH
• obezita farmakoterapie   MeSH
• topiramat MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• benzazepiny MeSH
• benzoxaziny MeSH
• bupropion MeSH
• cetilistat MeSH Prohlížeč
• fentermin MeSH
• fruktosa MeSH
• glukagonu podobný peptid 1 MeSH
• látky proti obezitě MeSH
• liraglutid MeSH
• lorcaserin MeSH Prohlížeč
• naltrexon MeSH
• topiramat MeSH

Pharmacotherapy of obesity should be an integral part of the comprehensive obesity management program which includes diet, exercise and cognitive behavioural intervention. Currently available antiobesity drugs result in only modest weight loss, however it is still accompanied by reduction of cardiometabolic health risks. In the past several antiobesity drugs were removed from the market because of serious adverse effects (psychostimulatory, cardiovascular, pulmonary hypertension, valvular disease, depression, addiction etc.). Such situations led some investigators and clinicians to nihilistic approaches to the drug treatment of obesity. This paper aims to review the data on clinical efficiency and safety of currently available antiobesity drugs and to summarize our knowledge on the recently discovered antiobesity agents which underwent clinical trials (such as lorcaserin, tesofensine, cetilistat, combination drugs, gut hormone analogues etc.). Approaches with two drug combination of decreased doses were recommended to increase both safety and efficacy of antiobesity treatment. However, previous experiences that antiobesity drug combinations (e.g. fenfluramine/phentermine) may also potentiate adverse events should be carefully considered in the evaluation of recently tested compounds. Administration of physiological doses of gut hormones - derived appetite regulating agents seems to be a promising, efficient, specific and thus, low side-effect approach in the treatment of obesity. To confirm the strong role of antiobesity drugs in the treatment of obesity and its complications further long-term studies evaluating their effect on morbidity and mortality end points in appropriate target populations are needed.

• MeSH
• látky proti obezitě škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• obezita farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• látky proti obezitě MeSH