Tirzepatide and blood pressure reduction: stratified analyses of the SURMOUNT-1 randomised controlled trial.

Background: Treating obesity may be a pathway to prevent and control hypertension. In the SURMOUNT-1 trial in people with obesity or overweight with weight-related complications, 72-week tirzepatide treatment led to clinically meaningful body weight and blood pressure reduction. Post hoc analyses were conducted to further explore the effects of tirzepatide on the pattern of blood pressure reduction and whether the effects were consistent across various subgroups.
Methods: The mixed effect for repeated measure model was used to compare changes in overall blood pressure, across demographic and clinical subgroups, baseline blood pressure subgroups and hypertension categories between SURMOUNT-1 participants randomised to treatment with tirzepatide and placebo. The association between weight changes and blood pressure and adverse events associated with low blood pressure were also evaluated by mediation analysis.
Results: Tirzepatide treatment was associated with a rapid decline in systolic and diastolic blood pressure over the first 24 weeks, followed by blood pressure stabilisation until the end of the observation period, resulting in a significant net reduction by 72 weeks of 6.8 mm Hg systolic and 4.2 mm Hg diastolic blood pressure versus placebo. Participants randomly assigned to any tirzepatide group were more likely than those assigned to placebo to have normal blood pressure at week 72 (58.0% vs 35.2%, respectively). The effects were broadly consistent across baseline blood pressure subgroups, shifting the blood pressure distribution curve to lower blood pressure levels. The mediation analysis indicated that weight loss explained 68% of the systolic and 71% of the diastolic blood pressure reduction. Low blood pressure adverse events were infrequent, but the rate was higher in the tirzepatide group.
Conclusions: In these post hoc analyses, in participants with obesity or overweight, tirzepatide was associated with reduced blood pressure consistently across participant groups primarily via weight loss, with relatively few blood pressure-related adverse events.
Trial Registration Number: NCT04184622.
Competing Interests: Competing interests: In the past 3 years, HMK received options for Element Science and Identifeye and payments from F-Prime for advisory roles. He is a co-founder of and holds equity in Hugo Health, Refactor Health, and ENSIGHT-AI. He is associated with research contracts through Yale University from Janssen, Kenvue, Novartis, and Pfizer. JAdL has received honoraria for participation in data safety monitoring committees from Eli Lilly and Company, Novo Nordisk, Amgen, Regeneron, AstraZeneca and Merck. NS has consulted for Abbott Laboratories, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Hanmi Pharmaceuticals, Janssen, MSD, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, Sanofi and received grant support paid to his university from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics. BL, PS, CJM, NNA, MCB and AS are employees and shareholders of Eli Lilly and Company.
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