Tirzepatide Provides Sustained BP Reduction in Overweight Adults

Along with reducing body weight, tirzepatide consistently lowers blood pressure across various subsets of nondiabetic patients with overweight or obesity, according to a post hoc analysis of the SURMOUNT-1 trial.

The effect was sustained through 72 weeks of treatment and was mostly—but not completely—explained by weight loss, researchers led by Harlan Krumholz, MD (Yale School of Medicine, New Haven, CT), report in a study published online recently in Heart.

BP-related treatment-emergent adverse events were infrequent, albeit more common with tirzepatide than with placebo (6.8% vs 3.3%).

“This analysis was crucial because treating obesity has been identified as a potential pathway to prevent and control hypertension, which is a leading global risk factor for cardiovascular disease and premature death,” Krumholz told TCTMD via email.

And these results, he said, are “paradigm-shifting, as these new medications may soon become the first step in effective hypertension control for people with obesity—delivering blood pressure reductions that rival those of traditional antihypertensive medications, along with many additional benefits.”

Clinically Meaningful Impact on BP

Prior research has shown that weight gain increases blood pressure and that substantial weight loss—with bariatric surgery or caloric restriction, for instance—reduces it. In addition, a recent meta-analysis suggested that semaglutide (Wegovy; Novo Nordisk), a glucagon-like peptide-1 (GLP-1) receptor agonist, lowers BP in patients without diabetes.

Tirzepatide, approved for the treatment of type 2 diabetes (sold as Mounjaro) and obesity (sold as Zepbound; both Eli Lilly), is an agonist of both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor. The main results of the SURMOUNT-1 trial showed that the drug, which was given in three doses (5, 10, and 15 mg) reduced both body weight and BP versus placebo in patients with overweight or obesity with weight-related complications (but not diabetes), although there was limited analysis of BP. A substudy involving ambulatory BP monitoring demonstrated consistent reductions in both daytime and nighttime systolic BP across subgroups at the 36-week mark.

The current post hoc analysis was performed to delve deeper into the BP effects across subgroups throughout the entire 72-week treatment period. It included 2,539 trial participants (mean age 45 years; 68% women) who had BP measurements performed at baseline and at least one other point during follow-up. At baseline, 32.3% had hypertension and 29.9% were taking antihypertensive medications; mean BP was 123.3/79.5 mm Hg. Mean body mass index BMI) was 38 kg/m².

Systolic and diastolic BP dropped significantly over the first 24 weeks in the tirzepatide-treated patients (by 7.8 to 8.5 mm Hg systolic and 3.9 to 4.4 mm Hg diastolic), with little change in the placebo group. There was a plateau in BP from that time point to 72 weeks, but the advantage for tirzepatide persisted. At the end of the study, the placebo-corrected reductions in systolic and diastolic BP with tirzepatide (all doses combined) were 6.8 and 4.2 mm Hg, respectively (P < 0.001 for both).

Patients were more likely to have normal BP at week 72 if they were treated with tirzepatide than if they received placebo (58.0% vs 35.2%).

This BP impact was relatively consistent across subgroups defined by sex, age, baseline BMI, and baseline BP, although there were significantly larger reductions in patients without diagnosed hypertension and in those not taking antihypertensive medications (P < 0.001 for both interactions).

“Greater reductions in antihypertensive medications in some tirzepatide recipients may contribute to this observed interaction, but we cannot exclude other explanations,” Krumholz et al write.

A mediation analysis indicated that weight loss explained 68% of the effect on systolic BP and 71% of the effect on diastolic BP.

In terms of safety, rates of BP-related adverse events were relatively low, with the most frequent being dizziness (4.6% with tirzepatide vs 2.3% with placebo). Four tirzepatide-treated patients had severe or serious treatment-emergent adverse events (0.2%): one case each of hypotension, syncope, presyncope, and loss of consciousness. There was no severe orthostatic hypotension in either the tirzepatide or placebo group.

A ‘Cardiovascular Health Drug’

Krumholz said it was surprising that weight loss didn’t explain all of the BP effect observed in the trial, a finding that suggests other mechanisms are at play, too.

“This effect could be related to the drug’s mechanisms, which might influence blood pressure regulation through pathways that are not entirely dependent on weight reduction, including, for example, reduction of inflammation,” he said. “We do not yet know what mechanisms are most important.”

Nonetheless, the BP reductions sustained over 72 weeks of treatment “are clinically meaningful,” particularly in light of the fact that most patients had readings in the normal range at baseline, Krumholz said. “These reductions exceed what is seen with many antihypertensive medications and have the potential to reduce the risk of major cardiovascular events.”

A key takeaway from this analysis, according to Krumholz, is that tirzepatide is not only a weight-loss drug, but also “a cardiovascular health drug.”

The combination of weight loss and BP reduction with tirzepatide makes it “a valuable option for patients with obesity, particularly those with or at risk for hypertension,” he said. “Clinicians might consider tirzepatide as part of a comprehensive approach to managing obesity and its related comorbidities, including hypertension. Furthermore, the observed blood pressure effects were consistent across different subgroups, indicating broad applicability.”

He and his colleagues note that these findings cannot be extrapolated to more-selective GLP-1 receptor agonists because tirzepatide also influences the GIP receptor.

Additional trials are ongoing to assess the impact of the drug on cardiometabolic outcomes, including SURMOUNT-MMO and SURPASS-CVOT.