Long-term effects of weight-reducing drugs in people with hypertension

This Cochrane review pooled eight randomised trials of weight-reducing drugs in about 13,000 adults with hypertension. For orlistat, phentermine/topiramate and naltrexone/bupropion, effects on death and cardiovascular disease were uncertain, though some drugs increased adverse events. Newer agents semaglutide and tirzepatide were included but reported no results for these critical outcomes.

Meta-analysis — systematic review and meta-analysis. Population: non-pregnant adults with essential hypertension in randomised controlled trials. Sample size: approximately 13,000 hypertensive participants. Follow-up: six to 48 months. Interventions: orlistat; phentermine/topiramate; naltrexone/bupropion; semaglutide; tirzepatide.

For orlistat, all-cause mortality and cardiovascular morbidity effects were very uncertain, but SAEs were probably increased (RR 1.45, 95% CI 1.10 to 1.91). Phentermine/topiramate showed very uncertain effects on mortality, cardiovascular morbidity and SAEs, but probably increased all AEs (RR 1.13, 95% CI 1.08 to 1.20). Naltrexone/bupropion showed very uncertain effects on mortality and cardiovascular morbidity, probably no difference in SAEs, but probably increased all AEs (RR 1.69, 95% CI 1.58 to 1.80). No results for these outcomes were reported for semaglutide or tirzepatide. Overall, evidence was insufficient to draw conclusions about mortality or cardiovascular morbidity benefits.

Researchers studying semaglutide, tirzepatide or liraglutide will find this review useful because it summarises the current trial evidence specifically in patients with hypertension, where separate data are often missing. For semaglutide and tirzepatide, no results on mortality, cardiovascular morbidity or adverse events were reported in the included trials. The review does not establish whether these drugs reduce cardiovascular risk in hypertension.

Key findings

• Orlistat probably increases serious adverse events compared with placebo (RR 1.45, 95% CI 1.10 to 1.91; 3 trials, 1476 participants).
• Phentermine/topiramate probably increases all adverse events compared with placebo (RR 1.13, 95% CI 1.08 to 1.20; 1 trial, 1305 participants).
• Naltrexone/bupropion probably increases all adverse events compared with placebo (RR 1.69, 95% CI 1.58 to 1.80; 1 trial, 8283 participants).
• Naltrexone/bupropion may have little to no effect on all-cause mortality compared with placebo, but the evidence is very uncertain (RR 0.99, 95% CI 0.70 to 1.40; 1 trial, 8283 participants).
• Eight RCTs including approximately 13,000 hypertensive participants evaluated orlistat, phentermine/topiramate, naltrexone/bupropion, semaglutide and tirzepatide.
• Included trials of semaglutide and tirzepatide reported no results for all-cause mortality, cardiovascular morbidity, serious adverse events or adverse events.

Limitations

• The authors state that evidence for people with hypertension remains insufficient to draw conclusions regarding mortality or cardiovascular morbidity benefits.
• Critical outcomes of death and cardiovascular complications were not the focus of the included trials and were sometimes presented only as adverse events, yielding very low certainty evidence.
• No RCTs have provided separate data for participants with hypertension for liraglutide, so liraglutide results could not be included.
• Seven of the eight included trials were funded by the pharmaceutical industry.

The record

• Journal: The Cochrane database of systematic reviews 6: CD007654
• Published: 2026-06-19
• PMID: 42318855 — DOI: 10.1002/14651858.cd007654.pub6
• MeSH terms: Humans, Cardiovascular Diseases, Hypertension, Obesity, Weight Loss, Phentermine, Cyclobutanes, Bupropion, Lactones, Naltrexone, Fructose, Anti-Obesity Agents, Drug Combinations, Cause of Death, Blood Pressure, Adult, Randomized Controlled Trials as Topic, Topiramate, Rimonabant, Orlistat, Tirzepatide, Semaglutide
• Author countries: Austria, Germany

Peptide profiles: Semaglutide, Tirzepatide, Liraglutide.

All indexed evidence: Semaglutide trials & papers, Tirzepatide trials & papers, Liraglutide trials & papers.

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