Yes, you may very well need to adjust antihypertensive regimen of patients who have experienced significant weight loss while on GLP-1RAs.^1,2  

In the STEP-1 trial evaluating the impact of semaglutide on cardiometabolic risk factors in adults who were overweight or obese, 34.3% of the group receiving semaglutide had either reduction in the dose or cessation of antihypertensive medications, compared to 15.6% in the placebo group.²  In SURMOUNT-1 trial examining the impact of tirzepatide on blood pressure reduction, a significant net reduction of 6.8 mm Hg systolic and 4.2 mm Hg diastolic blood pressure compared to placebo over 72 weeks was found; weight loss accounted for ~70% of systolic or diastolic blood pressure reduction. ²

The need to lower the dose of or discontinue antihypertensive medications in the setting of significant weight loss should not come as a surprise since this phenomenon predates the widespread use of GLP-1RA in obesity. ^1,3 However, in addition to their impact on blood pressure through weight loss, GLP-1RAs may  lower blood pressure through alternative  mechanisms, including natriuresis, direct vasodilation and reduction in sympathetic nervous system activity.⁴  It’s also important to remember that GLP-1RAs may reduce both systolic and diastolic blood pressures in patients with hypertension even before significant weight loss is observed! ⁵

But it’s not just about antihypertensive medications!  The use of GLP-1RAs with its attendant weight loss may also require dosage adjustment or discontinuation of several other commonly prescribed medications (eg, insulin, levothyroxine, and anticonvulsants, phenytoin, warfarin, lithium carbonate, and digoxin).² So don’t forget to regularly review the medication list of patients who have experienced recent weight loss on GLP-1RAs!

Bonus Pearl:  Did you know that the concept of incretin effect was first proposed in the 1970s based on observations that insulin secretion was 2-3 times higher after oral glucose intake than that after intravenous glucose administration? ⁵

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References

1. Manian FA. Antihypertensive medications in patients with weight loss. JAMA Intern Med 2025;185:475. Antihypertensive Medications in Patients With Weight Loss | JAMA Internal Medicine | JAMA Network
2. Karakus KE, Shah VN, Akturk HK. Tirzepatide-induced rapid weight loss-related thyrotoxicosis. JAMA Intern Med 2024;184:1246-1247. Tirzepatide-Induced Rapid Weight Loss–Related Thyrotoxicosis | Lifestyle Behaviors | JAMA Internal Medicine | JAMA Network
3. Shantha GPS, Kumar AA, Kahan S, et al. intentional weight loss and dose reductions of antihypertensive medications: a retrospective cohort study. Cardiorenal Med 2013;3:17-25. Intentional weight loss and dose reductions of antihypertensive medications: a retrospective cohort study – PubMed
4. Lingway I, Mosenzon O, Brown K, et al. Systolic blood pressure reduction with tirzepatide in patients with type 2 diabetes: insights from SURPASS clinical program. Cardiovasc Diabetol 2023;22:66. Systolic blood pressure reduction with tirzepatide in patients with type 2 diabetes: insights from SURPASS clinical program – PubMed
5. Liu QK. Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists. Front Endocrinol 2024; 15:1431292. Frontiers | Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists

Disclosures/Disclaimers: Reference 1 was written by this contributor. The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!