This review concluded that lorcaserin resulted in modest weight loss and appeared to be well tolerated. The authors' conclusions reflect the evidence presented, but it is unclear whether the small changes in weight, BMI and other outcomes measured as a result of treatment with lorcaserin represent clinically significant benefits.

To evaluate the effectiveness and safety of lorcaserin therapy in obese adults.

PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched without language restrictions for studies published between 1946 and July 2012; search terms were reported. Current Controlled Trials, US National Institutes of Health Clinical Trials Registry and the World Health Organization International Clinical Trials Registry were also searched. Reference lists of retrieved studies were scanned for additional studies.

Randomised controlled trials (RCTs) that evaluated the efficacy and/or safety of lorcaserin in obese adults (aged 18 to 65 years) with a body mass index (BMI) of 27 to 45kg/m², were eligible for inclusion. The primary outcomes were changes in weight and BMI.

All studies were conducted in the USA. The mean age of participants ranged from 41.3 to 53.2 years and the proportion of male participants from 13% to 46%. Baseline BMI ranged from 35.2 to 36.9kg/m² and baseline weight from 96.7 to 106kg. Where reported, lorcaserin was most commonly administered at 10mg two or four times a day. Most studies enforced a 600kcal deficit diet and exercise.

Two reviewers independently screened studies for inclusion.

Trial quality was assessed by two independent reviewers using the Jadad scale; scores of 3 or above (out of 5) were included. Two criteria were added to the assessment: level of blindness and the use of an intention-to-treat analysis.

Data for weight loss, percentage of cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, blood pressure, heart rate and adverse events were extracted by one reviewer and checked by a second. Relative risks were calculated for binary outcomes and mean differences for continuous outcomes.

Pooled relative risks or weighted mean differences were calculated along with 95% confidence intervals using a DerSimonian and Laird random-effects model. Heterogeneity was assessed using the Ι² statistic. Analyses were conducted on an intention-to-treat basis for primary outcomes; intention-to-treat was used for secondary analyses where available, otherwise completer analyses were conducted. Only studies with a duration of one year were included in the meta-analysis; other studies were combined in a narrative synthesis. Too few studies were included to assess publication bias.

Five RCTs met the inclusion criteria (8,315 patients; range 57 to 4,004). Two of the RCTs had follow-up less than one year (eight or 12 weeks), so three RCTs (7,789 patients) were included in the meta-analyses. One RCT scored 5, two scored 4 and two scored 3 on the Jadad scale; all trials scored 3 for level of blindness (all reported being double-blind) and four used an intention-to-treat analysis.

Lorcaserin resulted in a statistically significant additional weight loss of 3.23kg (95% CI 2.70 to 3.75; Ι² 59%) and reduction in BMI of 1.16kg/m² (95% CI 0.98 to 1.34; Ι² 62%) compared to placebo. Lorcaserin significantly decreased average waist circumference by 2.51cm (95% CI -3.04 to -1.99), systolic blood pressure by 0.61mmHg (95% CI -1.16 to -0.07), diastolic blood pressure by 0.49mmHg (95% CI -0.88 to -0.11), total cholesterol (WMD -1.06, 95% CI -1.07 to -0.42), low-density lipoprotein-cholesterol (WMD -1.29, 95% CI -2.32 to -0.25) and triglycerides (-4.70, 95% CI -6.53 to -2.87). There was no significant difference in the change in heart rate or high-density lipoprotein-cholesterol. Headache, nausea and dizziness were statistically significantly associated with lorcaserin. The results of sensitivity analyses were reported.

Two RCTs that compared lorcaserin to placebo had only short-term follow-up; one reported significant reductions in total cholesterol and low-density lipoprotein-cholesterol, and the other reported reductions in total cholesterol, high-density lipoprotein-cholesterol and triglycerides and a significant reduction in weight.

Lorcaserin resulted in modest weight loss and appeared to be well tolerated.

The review addressed a clear question supported by reproducible inclusion criteria. Relevant sources were searched, but only studies published in English were included, so publication and language bias could not be ruled out. The authors acknowledge potential for publication bias. Appropriate criteria were used to assess trial quality. Random-effects meta-analyses were conducted due to the presence of clinical heterogeneity; there were too few studies in these analyses to inform the distribution of effects required in a random-effects model.

The authors conclusions' reflect the evidence presented, but it is unclear whether the small changes achieved with lorcaserin compared to placebo in weight, BMI and other outcomes measured represent clinically significant benefits.

Practice: The authors did not state implications for practice.

Research: The authors recommended the conduct of clinical and pharmacovigilance studies with longer study durations to inform of the long-term efficacy and safety of lorcaserin. They also state that further investigation in different patient groups such as children and adolescents are needed.

None stated.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.