Effects of weight loss medications on mortality and cardiovascular events: A systematic review of randomized controlled trials in adults with overweight and obesity

Nutr Metab Cardiovasc Dis. 2021 Aug 26;31(9):2587-2595. doi: 10.1016/j.numecd.2021.05.023. Epub 2021 May 28.

Abstract

Aims: Adults affected by obesity are at higher risk of premature mortality. Medications can help to lose weight and to maintain weight loss. Aim of this meta-analysis was to assess whether anti-obesity medications affect all-cause mortality, mortality due to cardiovascular events, cardiovascular risk factors and body weight.

Data synthesis: A Medline search was performed to identify randomized controlled trials (RCTs) of anti-obesity medications in adults with overweight or obesity reporting data on all-cause mortality, cardiovascular mortality or non-fatal cardiovascular events, with a follow-up of at least 6 months. We identified 28 RCTs with 50,106 participants. The median follow-up was 52 weeks. Evidence did not show superiority of anti-obesity medications over placebo in reducing all-cause mortality (risk ratio 1.03, 95%Confidence Interval [CI] 0.87 to 1.21) or cardiovascular mortality (risk ratio 0.92, 95%CI 0.72 to 1.18). All-cause mortality rate was positively associated with weight loss (β = 0.0007; p = 0.045); hence, for each kg of body weight lost there was a 0.07% decrease of all-cause mortality. The pharmacological treatment reduced total-cholesterol (7.15 mg/dl; 95%CI 1.46-12.85), LDL-cholesterol (5.06 mg/dl; 95%CI 1.12-9.00), and triglycerides levels (9.88 mg/dl; 95%CI 5.02-14.75), while it increased HDL-cholesterol (1.37 mg/dl; 95%CI 0.17-2.57). Systolic blood pressure decreased (0.90 mmHg; 95%CI 0.15-1.64).

Conclusions: Although we were unable to demonstrate a superiority of anti-obesity medications over placebo on mortality, metaregression showed that even a small weight reduction tends to reduce all-cause mortality in obesity. Our data support public health measures to reduce the obesity burden by including the use of anti-obesity medications.

Registration number (prospero): CRD42020210329.

Keywords: Anti-obesity medications; Cardiovascular events; Meta-analysis; Mortality.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anti-Obesity Agents / adverse effects
  • Anti-Obesity Agents / therapeutic use*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control*
  • Female
  • Heart Disease Risk Factors
  • Humans
  • Male
  • Obesity / diagnosis
  • Obesity / drug therapy*
  • Obesity / mortality
  • Obesity / physiopathology
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Time Factors
  • Treatment Outcome
  • Weight Loss / drug effects*

Substances

  • Anti-Obesity Agents