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2016 ; 315
(22
): 2424-34
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Association of Pharmacological Treatments for Obesity With Weight Loss and
Adverse Events: A Systematic Review and Meta-analysis
#MMPMID27299618
Khera R
; Murad MH
; Chandar AK
; Dulai PS
; Wang Z
; Prokop LJ
; Loomba R
; Camilleri M
; Singh S
JAMA
2016[Jun]; 315
(22
): 2424-34
PMID27299618
show ga
IMPORTANCE: Five medications have been approved for the management of obesity,
but data on comparative effectiveness are limited. OBJECTIVE: To compare weight
loss and adverse events among drug treatments for obesity using a systematic
review and network meta-analysis. DATA SOURCES: MEDLINE, EMBASE, Web of Science,
Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial
registries. STUDY SELECTION: Randomized clinical trials conducted among
overweight and obese adults treated with US Food and Drug Administration-approved
long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion,
phentermine-topiramate, or liraglutide) for at least 1 year compared with another
active agent or placebo. DATA EXTRACTION AND SYNTHESIS: Two investigators
identified studies and independently abstracted data using a predefined protocol.
A Bayesian network meta-analysis was performed and relative ranking of agents was
assessed using surface under the cumulative ranking (SUCRA) probabilities.
Quality of evidence was assessed using GRADE criteria. MAIN OUTCOMES AND
MEASURES: Proportions of patients with at least 5% weight loss and at least 10%
weight loss, magnitude of decrease in weight, and discontinuation of therapy
because of adverse events at 1 year. RESULTS: Twenty-eight randomized clinical
trials with 29?018 patients (median age, 46 years; 74% women; median baseline
body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A
median 23% of placebo participants had at least 5% weight loss vs 75% of
participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible
interval [CrI], 6.63-12.85; SUCRA, 0.95), 63% of participants taking liraglutide
(OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55% taking naltrexone-bupropion (OR,
3.96; 95% CrI, 3.03-5.11; SUCRA, 0.60), 49% taking lorcaserin (OR, 3.10; 95% CrI,
2.38-4.05; SUCRA, 0.39), and 44% taking orlistat (OR, 2.70; 95% CrI, 2.34-3.09;
SUCRA, 0.22). All active agents were associated with significant excess weight
loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95% CrI,
-10.20 to -7.42 kg); liraglutide, 5.3 kg (95% CrI, -6.06 to -4.52 kg);
naltrexone-bupropion, 5.0 kg (95% CrI, -5.94 to -3.96 kg); lorcaserin, 3.2 kg
(95% CrI, -3.97 to -2.46 kg); and orlistat, 2.6 kg (95% CrI, -3.04 to -2.16 kg).
Compared with placebo, liraglutide (OR, 2.95; 95% CrI, 2.11-4.23) and
naltrexone-bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were associated with the
highest odds of adverse event-related treatment discontinuation. High attrition
rates (30%-45% in all trials) were associated with lower confidence in estimates.
CONCLUSIONS AND RELEVANCE: Among overweight or obese adults, orlistat,
lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide,
compared with placebo, were each associated with achieving at least 5% weight
loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the
highest odds of achieving at least 5% weight loss.
|*Weight Loss
[MESH]
|Anti-Obesity Agents/*adverse effects/therapeutic use
[MESH]
|Bayes Theorem
[MESH]
|Benzazepines/adverse effects/therapeutic use
[MESH]
|Drug Combinations
[MESH]
|Female
[MESH]
|Fructose/adverse effects/analogs & derivatives/therapeutic use
[MESH]
|Humans
[MESH]
|Lactones/adverse effects/therapeutic use
[MESH]
|Liraglutide/adverse effects/therapeutic use
[MESH]
|Male
[MESH]
|Middle Aged
[MESH]
|Naltrexone/adverse effects/therapeutic use
[MESH]
|Obesity/*drug therapy
[MESH]
|Orlistat
[MESH]
|Phentermine/adverse effects/therapeutic use
[MESH]