New Study Finds Tirzepatide Use Lowered Blood Pressure in Patients with Obesity

James A. de Lemos, MD
Credit: UT Southwestern Medical Center

The beneficial effects of tirzepatide (Mounjaro/Zepbound) may extend beyond weight loss and glucose control, with results of a new study suggesting use of the first FDA-approved GLP-1/GIP receptor agonist could also help lower blood pressure.

A substudy of the pivotal SURMOUNT-1 trial, results of the study suggest use of tirzepatide was associated with significant reductions in systolic blood pressure in adult patients with obesity, with results pointing to mean reductions of 7.4 mmHg with tirzepatide 5 mg, 10.6 mmHg with tirzepatide 10 mg, and 8.0 mmHg with tirzepatide 15 mg.¹

“Our findings indicate treating obesity with the weight loss medication tirzepatide may be an effective strategy for preventing or treating high blood pressure,” said lead investigator James A. de Lemos, MD, the Kern Wildenthal, MD, PhD, distinguished chair of cardiology and a professor of medicine at UT Southwestern Medical Center in Dallas.² “Although tirzepatide has been studied as a weight loss medication, the blood pressure reduction in our patients in this study was impressive. While it is not known if the impact on blood pressure was due to the medication or the participants’ weight loss, the lower blood pressure measures seen with tirzepatide rivaled what is seen for many hypertension medications.”

Although most of the headlines in the last half-decade related to type 2 diabetes and obesity management have centered around the effects of semaglutide, in the form of Ozempic and Wegovy, excitement surrounding the prospect of a dual-incretin agonist in tirzepatide has been growing since the first releases of data from the SURPASS and SURMOUNT programs, which were used to support approval in type 2 diabetes and chronic weight management, respectively.^3,4,5

Originally presented at the American Diabetes Association (ADA) 82nd Scientific Sessions in 2022, the phase 3 SURMOUNT-1 trial was designed as a double-blind, randomized, controlled trial to assess the effects of 5 mg, 10 mg, or 15 mg of tirzepatide once weekly relative to placebo for weight loss. The trial enrolled 2539 patients with a BMI of 30 kg/m2 or greater or 27 kg/m2 plus at least 1 weight-related complication, excluding diabetes, and randomized them in a 1:1:1:1 ratio to their aforementioned treatment options.⁴

A 72-week trial, results suggested the mean percentage change in weight at week 72 was −15.0% (95% Confidence Interval [CI], −15.9 to −14.2) with tirzepatide 5 mg, −19.5% (95% CI, −20.4 to −18.5) with tirzepatide 10 mg, and −20.9% (95% CI, −21.8 to −19.9) with tirzepatide 15 mg compared to −3.1% (95% CI, −4.3 to −1.9) with placebo (P <.001 for all). The trial, along with SURMOUNT-2, would go on to serve as the basis of the US Food and Drug Administration’s approval of tirzepatide for use as an adjunct to diet and exercise in chronic weight management in November 2023.^4,5

A planned substudy of the landmark trial, the current study included 600 patients from the trial and was designed to examine the effect of the dual GLP-1/GIP receptor agonist on blood pressure. As part of the substudy, all participants underwent 24-hour ambulatory blood pressure monitoring at baseline and week 36. For the purpose of analysis, all of the participants within the substudy had blood pressure levels less than 140/90 mmHg, and if they used blood pressure medications, they were required to have been taking their blood pressure medications for at least 3 months when the substudy began.¹

Among the 600 participants enrolled in the trial, 155 received placebo, 145 received tirzepatide 5 mg, 152 received tirzepatide 10 mg, and 148 received tirzepatide 15 mg. The cohort had mean age of 45.5 (Standard deviation [SD], 12.9) years, mean BMI of 37.4 (SD, 6.8) kg/m2, 68.7% were female, and 66.8% were White. Investigators pointed out 30% reported hypertension at baseline and 29% reported use of at least 1 antihypertensive medication. Of the 600 enrolled, 494 had valid data for ambulatory blood pressure at baseline and week 36. The cohort had an overall 24-hour diastolic blood pressure of 72.1 (SD, 7.7) mmHg, with no between-group differences.¹

Upon analysis, results suggested the placebo-adjusted systolic blood pressure changes from baseline were −7.4 (95% CI, −10.0 to −4.7) mmHg, −10.6 (95% CI, −13.2 to −8.0) mmHg , and −8.0 (95% CI, −10.6 to −5.4) mmHg for tirzepatide 5, 10, and 15 mg, respectively. Investigators highlighted pooled analysis indicated changes in 24-hour systolic blood pressure correlated with change in body weight (r = .31; P <.0001) and mediation analyses indicated changes in ambulatory systolic blood pressure were partially mediated by weight changes (percentage mediated, 70.0% [95% CI, 47.0–102.6]).¹

At week 36, the following differences were observed for change in 24-hour diastolic blood pressure from baseline relative to placebo therapy:¹

• Tirzepatide 5 mg: -2.0 (95% CI, -3.6 to -0.3) mmHg
• Tirzepatide 10 mg: -2.9 (95% CI, -4.5 to -1.3) mmHg
• Tirzepatide 15 mg: -0.5 (95% CI, -2.0 to 1.1) mmHg

Further analysis suggested these results were consistent across subgroups defined by clinically relevant factors, including age, sex, BMI, and hypertension-related factors.

Investigators noted heart rate increased with tirzepatide relative to placebo therapy, with increases of 2.1 (95% CI, 0.3 to 3.9), 2.3 (95% CI, 0.6 to 4.1), and 5.4 (95% CI, 3.6 to 7.1) beats per minute, respectively, with tirzepatide 5, 10, and 15 mg at week 36 compared to baseline. Investigators underlined an increase in heart rate was observed in other GLP-1 receptor agonist studies and changes in heart rate from baseline to week 72 in SURMOUNT-1 indicate the observed heart rate increase may attenuate with continued treatment.¹

Investigators called attention to multiple limitations within their study to consider before overinterpreting results. These included using a limited subset from the trial, only measuring ambulatory blood pressure at baseline and 36 weeks, and failure to measure changes in food intake and 24-hour urine sodium excretion.¹

“While the impact of each of these beneficial effects is individually important, many of these obesity-related complications act synergistically to increase the risk of cardiovascular disease. Thus, strategies that mitigate multiple obesity-related complications may reduce the risk of cardiovascular events,” said Michael E. Hall, MD, MS, chair of the writing group for the Association’s 2021 scientific statement on weight-loss strategies for prevention and treatment of hypertension and chair of the department of medicine at the University of Mississippi Medical Center.²

References:

1. de Lemos JA, Linetzky B, le Roux CW, et al. Tirzepatide Reduces 24-Hour Ambulatory Blood Pressure in Adults With Body Mass Index ≥27 kg/m2: SURMOUNT-1 Ambulatory Blood Pressure Monitoring Substudy. Hypertension. Published online February 02, 2024. doi:10.1161/HYPERTENSIONAHA.123.22022
2. American Heart Association. New weight loss medication may help lower blood pressure in adults with obesity. American Heart Association Newsroom. February 5, 2024. Accessed February 5, 2024. https://newsroom.heart.org/news/new-weight-loss-medication-may-help-lower-blood-pressure-in-adults-with-obesity.
3. Campbell P. Tirzepatide (Mounjaro) wins FDA approval for type 2 diabetes. HCP Live. May 13, 2022. Accessed February 3, 2024. https://www.hcplive.com/view/tirzepatide-wins-fda-approval-for-type-2-diabetes.
4. Campbell P. Surmount-1: Tirzepatide provides significant, sustained weight loss in obesity. HCP Live. June 4, 2022. Accessed February 2, 2024. https://www.hcplive.com/view/surmount-1-tirzepatide-provides-significant-sustained-weight-loss-in-obesity.
5. Campbell P. FDA approves Tirzepatide (Zepbound) for Chronic Weight Management. HCP Live. November 8, 2023. Accessed February 2, 2024. https://www.hcplive.com/view/fda-approves-tirzepatide-zepbound-chronic-weight-management.