GLP-1 obesity drugs linked to clinically relevant blood pressure reductions

A recent meta-analysis – presented at the European Congress on Obesity – has found that glucagon-like peptide-1 receptor agonists and related multi-hormone obesity drugs were associated with lower systolic blood pressure in adults living with overweight or obesity

A meta-analysis of 32 phase III studies involving 43,618 adults has found that contemporary obesity drugs used for weight loss were associated with a clinically relevant reduction in blood pressure, with systolic blood pressure reported to fall by 0.34 millimetres of mercury for each 1 per cent reduction in body weight.

The findings were presented at this year’s European Congress on Obesity in Istanbul, Turkey, which took place in May. The study was conducted by Dr Marcel Muskiet of Leiden University Medical Center in the Netherlands, Professor David Cherney of the University Health Network and the University of Toronto in Canada and colleagues.

Obesity and hypertension represent convergent public health challenges, as both contribute substantially to preventable cardiovascular disease and premature mortality. Clinical guidelines and physiological evidence have supported the management of overweight and obesity as an important strategy to reduce blood pressure and cardiovascular risk.

Glucagon-like peptide-1 (GLP-1) receptor agonists have become increasingly prominent in the treatment of obesity and type 2 diabetes. Dual agonists that target both GLP-1 and glucose-dependent insulinotropic polypeptide have also shown clinically meaningful effects on weight loss. In many studies, these agents have also been associated with reductions in blood pressure, although the extent to which this effect depends directly on weight loss has remained less clearly defined.

The research team said the emergence of additional obesity therapies, now often described as multi-hormone receptor modulators, has added further complexity. These agents may act beyond GLP-1 receptor agonism and may also target pathways involving hormones such as amylin and glucagon. To quantify the relationship between weight loss and blood pressure reduction could help clinicians to refine treatment targets and better understand the cardiovascular effects of contemporary anti-obesity medicines.

The authors conducted a meta-analysis of phase III clinical trial programmes to assess the relationship between weight reduction and blood pressure reduction with GLP-1 receptor agonists and multi-hormone receptor modulators in adults living with overweight or obesity. They extracted placebo-adjusted changes in body weight and blood pressure using treatment policy estimands*. In practical terms, this means the reported changes reflected the average effect among all participants assigned to each treatment group, even where some participants did not fully adhere to treatment or discontinued therapy. This approach is closer to a real-world estimate than an idealised measure of perfect use.

The primary time point for each trial was used as the endpoint. The researchers calculated pooled mean differences in body weight and blood pressure, as well as the relationship between changes in both measures, through statistical modelling.

The analysis included 32 phase III trials and 43,618 adults with overweight or obesity. The mean age of participants was 54 years, the mean body mass index was 35.5 kg/m², 50 per cent of participants were female and 9.2 per cent had type 2 diabetes. Baseline systolic blood pressure was 128 millimetres of mercury across 31 trials involving 42,211 participants. In 29 trials involving 41,827 participants, 59 per cent of participants were living with hypertension. The median duration of treatment was 66 weeks.

Across all agents and doses, placebo-adjusted mean weight loss was 10.9 per cent, accompanied by a systolic blood pressure reduction of 5.2 millimetres of mercury. The statistical analysis showed that 77 per cent of the variance in blood pressure reduction was explained by the magnitude of weight loss with GLP-1 receptor agonists or multi-hormone receptor modulators. This corresponded to a 0.34 millimetre of mercury reduction in systolic blood pressure for each one per cent reduction in body weight.

The relationship remained consistent after adjustment for study duration, baseline body mass index, sex distribution and diabetes status, at 0.36 millimetres of mercury per one per cent weight loss.

The authors said the findings also suggested that these drugs may have direct blood pressure effects beyond their effect on body weight. Such effects could plausibly involve relaxation of blood vessels, improved renal salt handling and reduced stress signalling, all of which may contribute to lower blood pressure.

“Across phase III 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 – blood pressure-lowering potential of these drugs,” the authors concluded.

“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 added.

The researchers noted that several trials have continued to investigate these effects. These include larger registration studies – such as ATTAIN-HYPERTENSION – and smaller studies to evaluate blood pressure alongside weight loss, such as SOLUTION-Pilot. Mechanistic studies in humans have also examined acute effects on cardiac and vascular function, kidney physiology and neurohormonal pathways.

The study had several limitations. The analysis used trial-level data rather than individual patient-level data, which limited the ability to account for differences between participants or to identify causal mechanisms. The included trials also varied substantially in their populations, treatments and study designs, which may have affected the precision of the estimates.

Effects on blood pressure were not the primary outcome in the included trials and changes in background antihypertensive medication may have influenced the findings. Differences in how outcomes were defined and measured across studies may also have introduced additional variability, although the overall results were consistent across multiple analyses.

* Estimands are precisely defined descriptions of what treatment effect a study is trying to estimate. In clinical trials, an estimand sets out the exact question behind a numerical result. It helps avoid vague statements such as ‘the drug reduced symptoms’ by specifying what outcome is being measured, in whom, under what conditions and how complications during the trial should be handled.

To read the abstract from the conference please click here