Weight loss and blood pressure lowering with GLP-1 receptor agonists and multi-hormone receptor modulators in overweight and obesity: a systematic review and meta-regression of phase 3 clinical trials

Background Obesity and hypertension frequently coexist, and weight-reduction is recommended as a core strategy for blood pressure (BP) management in adults with overweight or obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and emerging multi-hormone receptor modulators (MHRMs) induce substantial weight loss alongside modest BP reductions. However, the extent to which weight-loss is associated with BP lowering across these therapies remains unclear. Methods We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials evaluating GLP-1RAs and MHRMs in adults with overweight or obesity (PROSPERO: CRD420251146441). We searched Ovid MEDLINE, Ovid Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials from 1946 to December 2025. Risk of bias was assessed using the revised Cochrane Risk of Bias tool. Placebo-adjusted changes in body weight and BP at each trial's primary endpoint were pooled using random-effects meta-analysis with inverse-variance weighting. Meta-regression assessed the association between weight loss and BP reduction. Findings Thirty-seven trials including 50,171 participants were analysed. Thirty-six trials had low risk of bias across all domains. Across all trials, 50% of participants were females, 16% had type 2 diabetes and 57% had hypertension. Median treatment duration was 68 weeks. Mean placebo-adjusted weight loss was −10.1% (95% CI −11.3 to −9.0) accompanied by a −4.9 mmHg (95% CI −5.5 to −4.3) reduction in systolic BP. Between-trial meta-regression showed that 76% of the variance in systolic BP reduction was explained by differences in weight loss (R 2 = 0.76; P < 0.01), corresponding to a reduction of 0.37 mmHg (95% CI 0.28 to 0.45) per 1% change in body weight. Interpretation Across phase 3 trials of GLP-1RAs and MHRMs, greater weight loss was strongly associated with larger reductions in BP, supporting pharmacological weight-loss therapies as an adjunct strategy for BP management in obesity. Funding None.