GLP-1/GIP receptor agonist has antihypertensive benefit


By Michael Woodhead

13 Feb 2024

The GLP-1/GIP receptor agonist diabetes medication tirzepatide has an antihypertensive benefit in addition to its weight loss effects in people with obesity, a new study shows.

The findings come from a trial (link here) involving almost 500 patients with obesity (average BMI 37.4 kg/m2) but no diabetes who were treated with tirzepatide for eight months and who underwent 24-hour ambulatory BP monitoring at the start and end of the study.

Participants received weekly injection doses of tirzepatide (5 mg, 10 mg or 15 mg) or placebo for 36 weeks. About one-third of participants had treated hypertension at baseline, and all had a BP less than 140/90 mm Hg.

As expected, at the 36-week follow-up, there was significant weight loss in the tirzepatide group: 15%, 19.5%, and 20.9% for the 5 mg, 10 mg, or 15 mg dose groups, respectively, compared to placebo.

At baseline, the mean (SD) 24-hour systolic BP was 124.6 (10.4) mmHg for the patient cohort. After 36 weeks of treatment with tirzepatide, there were significant dose-related reductions in 24-hour systolic BP in all treatment groups compared with placebo. The placebo-adjusted systolic BP change from baseline was −7.4 (95% CI, −10.0 to −4.7) mmHg for 5mg tirzepatide, −10.6 (95% CI, −13.2 to −8.0) mmHg for 10-mg and −8.0 (95% CI, −10.6 to −5.4) mmHg for 15-mg tirzepatide.

The results were consistent for both day and night-time BP, with significant reductions versus placebo for each tirzepatide dose. There were no associations between systolic BP reduction and factors such as age, sex, BMI, systolic BP, presence of hypertension, antihypertensive medication use or glycaemic status.  However, there was a suggestion that changes in 24-hour systolic BP  were partially mediated by weight change, with a significant correlation between changes in SBP and changes in body weight (r=0.31; P<0.0001).

For diastolic BP there were significant reductions from the baseline level of 72.1  (7.7)  mmHg in the 5 mg (−2.0 mmHg) and 10 mg (−2.9 mmHg) but not 15 mg (−0.5 mmHg) tirzepatide dose groups.

At 36 weeks, heart rate increased with tirzepatide versus placebo by  2.1, 2.3, and  5.4 beats per minute,  respectively, with tirzepatide 5, 10, and 15 mg.

The study investigators said the findings of a reduction in nighttime  systolic  BP was particularly significant as this was a stronger predictor for cardiovascular death and all-cause death than daytime and 24-hour systolic  BP.

And while there was some suggestion that tirzepatide-induced body weight reduction effects were associated with BP reductions, the drug may also have effects on BP independent of weight loss, they said.

This might be because tirzepatide was both a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist as well as a GLP-1 (glucagon-like  peptide-1)  receptor  agonist, the authors postulated.

“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 study author Professor James A. de Lemos, head of cardiology at UT Southwestern Medical Center in Dallas, Texas.

“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 rivalled what is seen for many hypertension medications,” he added.

The results were derived from a pre-planned substudy of the larger SURMOUNT-1 randomised control trial investigating increasing doses of tirzepatide on weight loss. Of the study participants 69% were female and the average age was 45.5 years.

“Overall, these data are encouraging that novel weight-loss medications are effective at reducing body weight, and they are also effective at improving many of the cardiometabolic complications of obesity, including hypertension, type 2 diabetes and dyslipidemia, among others,”  said Professor Michael E. Hall,  chair of the writing group for the American Heart 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 in Jackson, Mississippi.

“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,” he said.

“Additional studies will be necessary to determine the long-term impact on cardiovascular events such as heart attack and heart failure. Also, studies are needed to investigate what happens to blood pressure when medications like tirzepatide are discontinued – does the blood pressure rebound and go back up, or does it remain lowered?” Professor Hall concluded.

The study, published in Hypertension, was funded by Eli Lilly, the manufacturer of tirzepatide.

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