Weight Loss, Not GLP-1 Therapy, Predicts Systolic Blood Pressure Change in Diabetes

New results suggest that weight loss is the primary driver of changes in systolic blood pressure in adults with diabetes, not GLP-1 therapy selection, with each pound of weight loss associated with a 0.179 mmHg reduction in systolic blood pressure (P <.001).

The findings were presented at the Endocrine Society (ENDO) 2026 Annual Meeting by Thomas Edward Blakely, BS, MS candidate at the University of California, San Francisco (UCSF).

GLP-1 receptor agonists are an important class of therapeutics for diabetes management, showing improvements in glycemic control, body weight reduction, cardiovascular outcomes, and potential neuroprotective effects for this patient population. They also reduce systolic blood pressure, with some clinical trials suggesting that 10% to 30% of the changes act through weight-independent pathways.

“FDA-approved weight management GLP-1 therapies differ substantially in weight-loss efficacy, but whether this difference manifests in differential blood pressure changes after accounting for weight change is understudied,” Blakely and colleagues wrote.

To address this gap in research, Blakely and colleagues conducted a retrospective cohort study to assess 6-month changes in blood pressure and weight in adults with diabetes starting a US Food and Drug Administration (FDA)-approved GLP-1 weight-management therapy, including liraglutide, semaglutide, and tirzepatide. Their secondary aim was to compare systolic blood pressure change across therapies after accounting for weight loss.

Investigators assessed medication adherence by calculating the proportion of days covered (PDC) following the first 90 days of therapy, with analysis restricted to patients with a PDC ≥0.80. Follow-up measurements of weight and blood pressure were the closest records after 6 months of GLP-1 use, within a 90-day window. They used propensity score-weighted linear regression models to compare changes in systolic blood pressure across the therapies.

The study cohort included 361 patients who had ≥6 months of data before and after treatment initiation. Overall, the cohort had a mean age of 53.1 years and was 65.9% female. Most patients (95.0%) had a baseline BMI >30 kg/m², with a baseline systolic blood pressure of 127.1 (15.7) mmHg and diastolic blood pressure of 75.1 (10.7) mmHg. In total, 48 patients were on liraglutide, 210 were on semaglutide, and 103 were on tirzepatide.

At 6 months, mean weight change was −21.4 (17.8) lb, with 70.4% of patients achieving ≥5% weight loss and 46.3% achieving ≥10% weight loss. Systolic blood pressure decreased by 3.6 (17.2) mmHg and diastolic blood pressure by 0.7 (13.2) mmHg.

In correlation analysis, investigators observed a significant association between weight change and systolic blood pressure reduction (r = 0.138; P = .009), but not diastolic blood pressure (r = 0.079; P = .136).

In the propensity score-weighted regression model (adjusted R² = 0.360), changes in systolic blood pressure did not differ significantly between GLP-1 therapies after adjusting for weight loss, baseline measures, demographics, and comorbidities. As noted, each pound of weight loss was associated with a 0.179 mmHg reduction in systolic blood pressure (P <.001).

“In adults with diabetes, systolic blood pressure changes did not significantly differ by GLP-1 therapy selection after adjusting for weight loss,” investigators concluded. “Our results suggest that weight change is the primary driver of systolic blood pressure changes.”

References

1. Blakely T, Zhou C, Shin J, et al. Blood Pressure and Weight Outcomes Following First-Time Use of GLP-1 Therapies in Adults with Diabetes. Poster presented at: ENDO Annual Meeting; June 2026; Chicago, IL.

2. Darwish R, Abu-Sharia G, Butler AE. History of glucagon-like peptide-1 receptor agonists. Pharmacological Research. Published online November 26, 2025:108045. doi:https://doi.org/10.1016/j.phrs.2025.108045