乌鸦传媒

The once-weekly injectable tirzepatide (Mounjaro, Zepbound) was associated with reduced blood pressure (BP) in a prospective substudy of the SURMOUNT-1 trial.

Depending on the dose of the combination glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, patients with obesity had their average baseline mean 24-hour BP of 124.6/72.1 mm Hg brought down to various degrees by week 36:

• Decrease of 7.4/2.0 mm Hg with tirzepatide 5 mg, placebo adjusted
• Decrease of 10.6/2.9 mm Hg with tirzepatide 10 mg, placebo adjusted
• Decrease of 8.0/0.5 mm Hg with tirzepatide 15 mg, placebo adjusted

Researchers reported significant reductions in systolic BP on 24-hour ambulatory BP monitoring (ABPM) comparing each tirzepatide dose against placebo. Results were consistent for both day and nighttime BP -- the latter known to be "a stronger predictor for cardiovascular death and all-cause death," according to Bruno Linetzky, MD, PhD, the head of Eli Lilly and Company's tirzepatide research and development program in Buenos Aires, Argentina, and colleagues.

"This study demonstrates that tirzepatide improves 24-hour BP in obesity-related hypertension. While being consistent with in-office measurement, the current study uses a method that is superior to office BP alone for predicting cardiovascular risk," study authors reported in the journal .

Tirzepatide is currently FDA approved for type 2 diabetes and chronic weight management. The agent is reportedly than competing GLP-1 receptor agonists for weight loss.

"These data suggest that not only do medications for obesity treat the disease of obesity but they also improve our cardiovascular outcomes," commented Angela Fitch, MD, president of the Obesity Medicine Association and chief medical officer of the Knownwell clinic in Needham, Massachusetts, in a statement.

"We have known for years clinically that these newer GLP-1 medications lower blood pressure and we have to be mindful of that when caring for patients as many patients with overweight or obesity have [hypertension] and may take medications for blood pressure," Fitch continued. "This highlights why comprehensive care is important for patients with obesity as we often need to de-prescribe anti-hypertensive medications during obesity treatment to prevent blood pressure going to [sic] low."

The present BP data came from the SURMOUNT-1 trial of individuals with obesity (BMI at least 27 kg/m²) without type 2 diabetes. The substudy included patients with ABPM available at baseline and week 36 who had been randomly assigned to four treatment groups: placebo (n=155), tirzepatide 5 mg (n=145), tirzepatide 10 mg (n=152), and tirzepatide 15 mg (n=148).

The main finding of SURMOUNT-1 was that people with overweight or obesity shed substantial weight on the 15 mg dose of tirzepatide. Subsequently, the SURMOUNT-2 trial reported that people with overweight or obesity and type 2 diabetes taking the same dose also lost significant weight.

More recently, tirzepatide was associated with additional weight loss in people who already shed some pounds through a diet and exercise intervention in the SURMOUNT-3 trial. And for those discontinuing tirzepatide in SURMOUNT-4, most people rebounded in body weight.

As expected with a GLP-1 receptor agonist, gastrointestinal-related side effects have been commonly reported during the clinical trials, especially during the uptitration phase.

For the present SURMOUNT-1 substudy, investigators enrolled people with BP <140/90 mm Hg and stable antihypertensive therapy, if used. Patients also had to have at least 70% valid readings on ABPM and a minimum of 20 daytime (from readings every 30 minutes) and seven nighttime readings (from readings every 60 minutes) in order to be included.

The 600-person cohort averaged 45.5 years old and a BMI of 37.4. Nearly 70% were women. Hypertension was reported in 30% of the group at baseline, and 29% reported using a BP-lowering medication.

Ultimately, 494 individuals had valid ABPM data at baseline and week 36.

Linetzky and colleagues reported no significant interactions by baseline age, sex, BMI, systolic BP, the presence of hypertension, antihypertensive medication use, or glycemic status for the change in 24-hour mean systolic BP associated with tirzepatide.

Mediation analyses suggested that the BP reduction was not wholly attributed to weight loss, but that tirzepatide may also have effects on BP independent of weight reduction.

In any case, the present report was inherently limited by being a subset analysis and relying on just two BP readings for each person. Additionally, the investigators acknowledged that they did not account for changes in eating habits among participants.

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