A meta-analysis of 32 studies and 43,618 adults presented at this year's European Congress on Obesity in Istanbul, Turkey (12-15 May) shows that use of new classes of obesity drugs for weight loss is associated with a clinically relevant drop in blood pressure (BP): a 0.34 mmHg reduction in systolic BP per 1% weight loss. The study is by Dr Marcel Muskiet at the Leiden University Medical Center, Leiden, The Netherlands and Professor David Cherney and colleagues from the University Health Network / University of Toronto, Ontario, Canada.
Obesity and high blood pressure (hypertension) are converging public health crises that contribute to preventable cardiovascular disease and deaths. Epidemiological and physiological evidence, and clinical guidelines, support the management of overweight and obesity as a central strategy for blood pressure (BP) reduction.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs), as well as newer dual agonists targeting both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), can induce clinically meaningful weight loss with accompanying BP reductions, varying by agent and diabetes-status. However, the relationship between weight loss and BP reduction remains incompletely defined, as these drugs exert both weight-dependent and -independent effects.
The emergence of additional agents (the now broadly referred to as multi-hormone receptor modulators; MHRMs), including those drugs targeting pathways such as amylin and glucagon, has added further complexity. These therapies extend beyond GLP-1R-agonism by simultaneously engaging with other hormone receptors. Quantifying this relationship may refine therapeutic weight and BP targets and clarify the BP benefits of contemporary weight-loss drugs.
The authors conducted a meta-analysis of phase 3 clinical trial programs to quantify the relationship between weight loss and BP lowering with GLP-1RAs and MHRMs in adults living with overweight or obesity. Placebo-adjusted change in body weight (BW) and BP were extracted using treatment policy estimands (this means the reported changes in body weight and blood pressure reflect the average effect in all participants assigned to each group, even if some did not fully follow the treatment or discontinued it - similar to a "real-world" effect rather than a perfect-use scenario). The primary timepoint for each trial was used as the endpoint. Pooled mean differences in BW and BP, and the changes in both, were calculated using statistical modelling.
The analysis included 32 phase 3 trials, encompassing 43,618 adults with overweight or obesity. Mean age was 54 years, mean BMI was 35.5 kg/m², 50% were female, and 9.2% had type 2 diabetes. Baseline systolic BP was 128 Hg (31 trials; n=42,211), with 59% of participants living with hypertension (29 trials; n=41,827). Median treatment duration was 66 weeks. Across all agents and doses, placebo-adjusted mean weight loss was –10.9% accompanied by a systolic BP reduction of –5.2 mmHg. The statistical analysis (Figure in full abstract) showed that 77% of the variance in BP reduction was explained by the magnitude of weight loss with GLP-1RAs/MHRMs, corresponding to a 0.34 mmHg reduction in systolic BP per 1% weight loss. This relationship remained consistent after adjustment for study duration, baseline BMI, sex distribution, and diabetes status (0.36 mmHg/ per 1% weight loss)
The authors say that even without weight loss (these drugs may directly relax blood vessels, improve kidney salt handling, and reduce stress signals in the body, all of which can help lower blood pressure.
The authors conclude: "Across phase 3 trials of GLP-1 receptor agonist and multi-hormone receptor modulator obesity drugs in adults with overweight or obesity, the magnitude of blood pressure-lowering was closely associated with the degree of weight loss, highlighting the clinically relevant –yet often underappreciated– BP-lowering potential of these drugs.
"These findings support a meaningful role for these medications in blood pressure management in overweight and obesity, and underscore the need for targeted mechanistic and clinical studies to calculate weight-dependent and weight-independent effects."
They note several such trials are ongoing to investigate these effects, including both larger clinical (registration) trials (such as ATTAIN-HYPERTENSION) and smaller studies that evaluate blood pressure alongside weight loss (e.g., SOLUTION-Pilot). In addition, there are mechanistic studies in humans focusing on acute effects on cardiac and vascular function, kidney physiology, and neurohormonal pathways.
This study has several limitations. First, the analysis was based on trial-level rather than individual patient-level data, which limits the ability to account for differences between participants or identify causal mechanisms. Second, there was substantial variability across trials in terms of populations, treatments, and study design, which may influence the precision of the estimates. Third, blood pressure was not the primary outcome in the included trials, and changes in background antihypertensive medications may have affected results. Finally, differences in how outcomes were defined and measured across studies may have introduced additional variability, although the overall findings were consistent across multiple analyses.
