Lorcaserin for body weight reduction : A systematic review and meta-

analysis

Leite, B.F.1 ; Leão, L.S.C. 1 ; Buehler A. M. 2; Pereira T. V. 2

1 Brazilian Ministry of Health 2 Hospital Alemão Oswaldo Cruz

INTRODUCTION

According to the World Health Organization (WHO), obesity worldwide has almost doubled since

1980. Currently, most European countries have a prevalence of overweight (BMI ≥ 25) or obese (BMI ≥ 30)

ranging between 50% and 66% of the population, as in America, countries like the United States and Brazil

this prevalence is 67% and 40%1. A nonlinear regression study estimates a 33% increase in the prevalence

of adult obesity and 130% in the prevalence of severe obesity over the next two decades2.

The increased concern about obesity comes from its increasing prevalence and now represents a

threat to public health3,4. Overweight and obesity are associated with increased risk of developing other

chronic diseases such as type 2 diabetes mellitus, dyslipidemia, systemic hypertension, cardiovascular

disorders, skeletal muscle disorders (such as osteoarthritis), obstructive apnea sleep, some cancers and

mortality. This fact also implies high costs for the health system, patients and society as well as loss of quality

of life due to obesity and its comorbidities 5.

The main goal of treatment for obesity either surgical or medical (non-surgical) is to reduce the

weight and body mass indict (BMI), lower waist circumference, achieving partial or total remission of T2DM

and control the metabolic syndrome and hypertension. In Brazil, drug treatment possibilities have become

increasingly restricted. Recently, ANVISA introduced again in the market derivatives amphetamine

(fenproporex, mazindol and amfepramone) after three years of withdrawal from the market for safety

reasons.

New technologies are highly desirable in the treatment of this disease, but not all medications are

indicated for all patients and safety issues should be an additional concern about the success of treatment. In

this regard, the objective of this systematic review is to summarize the available evidence on the lorcaserin, a

selective serotonin 2C receptor agonist used in the treatment of obesity.

METHODS

Following the methodological guidelines for the development of PTC Ministry of Health, was first

drafted the guiding question of the study through the PICO, then a search was conducted in the main

databases (PubMed, Embase, Cochrane, Lilacs and CRD). Each study recovered in the databases was

selected and evaluated by two independent researchers, their inconsistencies resolved by consensus, when

there was no consensus, the assessment of a third investigator was requested. To assess the risk of bias on

the results found in the selected studies, we used the Cochrane Collaboration tool for assessing the risk of

bias in randomized clinical trials6.

Statistical analysis was performed using Review Manager 5.3 (RevMan). The evaluated outcomes

were summarized quantitatively using the Mantel-Haenszel model for the variables calculated by measuring

the relative risk, and the inverse of the variance for the variables calculated by the average difference metric.

Both models were calculated using the random effect. Heterogeneity between the results of the pooled

studies was assessed by the degree of inconsistency (I2), and confirmed the significant heterogeneity by

Cochran Q test with P <0.1.

It found a total of 555 articles through research carried out in the aforementioned databases. After

deleting the duplicate studies, was conducted a pre-selection of independent double check by reading the

title and abstract, 424 were excluded because they are not relevant to the proposed objective, leaving 18

potentially eligible studies to complete reading. Carried out a complete reading of the articles, 5 studies met

eligibility criteria and were included in the systematic review.

Lorcaserin for body weight reduction : A systematic review and meta-

analysis.

Leite, B.F.1 ; Leão, L.S.C. 1 ; Buehler A. M. 2; Pereira T. V. 2

1 Brazilian Ministry of Health 2 Hospital Alemão Oswaldo Cruz

RESULTS

Most of the trials had 3 comparative groups, evaluating the medication used once and twice daily

compared to placebo. We first compared the two active groups and if there were no differences between

then, we grouped them in only one. If we identified statistical differences between the two dosages, we

considered the results by dosage.

For the body weight reduction, lorcaserin administrated once a day reduced the body weight by

1.95 kilograms [Kg, (95% CI -2.71;-1.18); I2 = 55%]. Lorcaserin administrated twice daily reduced the body

weight by 2.74 kilograms [95% CI (-3.24;-72.23); I2=25%]. Lorcaserin showed a positive and significant effect

for all the others outcomes investigated.

RESULTS

Despite the profile of the adverse reaction were mild, it increased the risk for the most adverse

reaction commonly reported by the trials.

Considering that the medication is not commercially available, it is not possible to estimate the

treatment cost and its cost-effectiveness. Furthermore, since this is a new technology, long-term follow up

studies and cost-effectiveness analysis are high desirable to better understanding the effect of lorcaserin on

body weight.

Adverse events Total Events -

Lorcaserin

Total Events - Placebo

I² (%)

Relative Risk

Headache

781 361 0 1,68 [1,49 – 1,89]

Upper respiratory infection

562 402 79 1,00 [0,72 – 1,39]

Nasopharyngitis 573 417 19 1,08 [0,94 – 1,25]

Dizziness 365 138 34 1,97 [1,50 – 2,59]

Nausea 380 194 6 1,49 [1,25 – 1,79]

Diarrhea 265 186 59 1,06 [0,76 – 1,49]

Urinary tract infection

315 193 0 1,28 [1,07 – 1,52]

Fatigue 315 127 0 1,89 [1,55 – 2,31]

Total (95% CI)

Lorcaserin for body weight reduction : A systematic review and meta-

analysis

Leite, B.F.1 ; Leão, L.S.C. 1 ; Buehler A. M. 2; Pereira T. V. 21 Brazilian Ministry of Health 2 Hospital Alemão Oswaldo Cruz

REFERENCES

1 . World Health Organization. WHO global database on body mass index. http://apps.who.int/bmi/index.jsp.

2. Finkelstein EA, Khavjou OA, Thompson H, et al. Obesity and severe obesity forecasts through 2030. Am J Prev Med. Jun; 2012 42(6):563–570.

3. Gallagher EJ, Leroith D, Karnieli E. The metabolic syndrome — from insulin resistance to obesity and diabetes. Med Clin North Am 2011; 95:855-73.

4. Garber AJ. Obesity and type 2 diabetes: Which patients are at risk? Diabetes Obes Metab 2012;14:399-408.

5. Picot J, Jones J, Colquitt JL, Gospodarevskaya E, Loveman E, Baxter L, et al. The clinical effectiveness and cost-effectiveness of bariatric (weight loss) surgery for obesity: a systematic review and economic evaluation.

Health Technol Assess 2009;13:1-190, 215-357, iii-iv.

6. Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. http://www.cochrane-handbook.org. Updated March 2011. Accessed November 07,

2014.