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Evidence summaries

Effect of Weight-Reducing Drugs in Hypertensive Patients

Orlistat appears to reduce weight and blood pressure and naltrexone/bupropion appears to reduce weight but not blood pressure in patients with hypertension. Effect on mortality and cardiovascular morbidity is unclear. Level of evidence: "B"

The quality of evidence is downgraded by imprecise results (few patients and outcome events).

Summary

A Cochrane review [Abstract] 1 included 6 studies with a total of 12 724 adult subjects with hypertension. The aim was to assess long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension. Four studies compared orlistat to placebo (n=3 132, mean age 46 to 55 years), 1 study compared phentermine/topiramate to placebo (n=1 305, mean age 53 years), and 1 study compared naltrexone/bupropion to placebo (n=8 283, mean age 62 years). No relevant studies investigating liraglutide or lorcaserin in people with hypertension were indentified.

Orlistat compared to placebo: Orlistat lowered body weight more effectively than placebo (MD −3.7 kg, 95% CI −4.7 to −2.8, statistical heterogeneity I2 =68%; 4 studies, n=2 080) after a study duration of 6 to 12 months. After 6 to 12 months, orlistat reduced systolic blood pressure (MD −2.6 mm Hg, 95% CI −3.8 to −1.4 mm Hg) and diastolic blood pressure (MD −2.0 mm Hg, 95% CI −2.7 to −1.2 mm Hg; 4 studies, n=2 058) compared to placebo. Gastrointestinal side effects were more common with orlistat compared to placebo. Serious adverse events (SAEs) were more common in participants treated with orlistat compared to those who received placebo (RR 1.45, 95% CI 1.10 to 1.91; 3 studies, n=1 476).

Naltrexone/bupropion compared to placebo: Naltrexone/bupropion led to a significantly greater reduction in body weight (−1.9 kg versus −0.0 kg, p < 0.001; 1 study, n=8 283) compared to placebo. There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo. There were no differences in the rates of all-cause mortality (RR 0.99, 95% CI 0.70 to 1.40), cardiovascular morbidity (RR 1.11, 95% CI 0.87 to 1.41), or serious adverse events (RR 1.05, 95% CI 0.96 to 1.14) between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion (RR 1.69, 95% CI 1.58 to 1.80).

Comment: The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns.

References

  • Siebenhofer A, Winterholer S, Jeitler K et al. Long-term effects of weight-reducing drugs in people with hypertension. Cochrane Database Syst Rev 2021;(1):CD007654. [PubMed]

Primary/Secondary Keywords