Tirzepatide lowered 24-hour blood pressure in SURMOUNT-1 substudy

A planned substudy of the SURMOUNT-1 trial found that weekly tirzepatide lowered 24-hour blood pressure in adults with overweight or obesity, with reductions the lead investigator said are in the range seen with standard blood pressure medicines ^[1][2]. The results were published online in the journal Hypertension on February 2, 2024 ^[1].

What the substudy measured

SURMOUNT-1 was a 72-week, double-blind, randomized trial that enrolled 2,539 adults with a body mass index of 30 kg/m2 or higher, or 27 kg/m2 or higher plus at least one weight-related condition, and without diabetes ^[1]. Participants received tirzepatide 5 mg, 10 mg or 15 mg once weekly, or placebo ^[1]. Mean weight change at week 72 was −15.0% at 5 mg, −19.5% at 10 mg and −20.9% at 15 mg, compared with −3.1% on placebo ^[1].

The substudy enrolled 600 of those participants — 155 assigned placebo, 145 to tirzepatide 5 mg, 152 to 10 mg and 148 to 15 mg — and used 24-hour ambulatory blood pressure monitoring at the start and again at week 36 ^[1][2]. Ambulatory monitoring records pressure across a full day and night rather than a single office reading. To take part, patients had to have blood pressure below 140/90 mmHg, and anyone using blood pressure medication had to have been on a stable regimen for at least three months ^[1][2]. Of the 600, 494 had valid ambulatory readings at both time points ^[1].

Mean age was 45.5 years, mean BMI was 37.4, and 68.7% of participants were female; 30% reported high blood pressure at the start and 29% reported taking at least one blood pressure drug ^[1].

What it found

Compared with placebo, the change in 24-hour systolic blood pressure from baseline to week 36 was −7.4 mmHg (95% CI, −10.0 to −4.7) at 5 mg, −10.6 mmHg (95% CI, −13.2 to −8.0) at 10 mg and −8.0 mmHg (95% CI, −10.6 to −5.4) at 15 mg ^[1][2]. The average baseline 24-hour systolic reading was 124.6 mmHg, with no differences between groups at the start ^[2]. Results were consistent for daytime and nighttime pressure, and across subgroups defined by age, sex, BMI and hypertension-related factors ^[1][2].

The corresponding changes in 24-hour diastolic blood pressure were −2.0 mmHg at 5 mg, −2.9 mmHg at 10 mg and −0.5 mmHg at 15 mg; the 15 mg result had a confidence interval that crossed zero (−2.0 to 1.1) ^[1].

Heart rate rose with tirzepatide compared with placebo, by 2.1 beats per minute at 5 mg, 2.3 at 10 mg and 5.4 at 15 mg ^[1][2]. The researchers noted that heart rate increases have appeared in other GLP-1 studies and that in the main SURMOUNT-1 trial the increase appeared to lessen by week 72 ^[1].

An analysis suggested the blood pressure changes were partly explained by weight loss, with an estimate that 70.0% of the effect was mediated by weight change and a wide confidence interval of 47.0% to 102.6% ^[1]. Changes in weight and in 24-hour systolic pressure were correlated (r = .31; P < .0001) ^[1].

“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,” said lead investigator James A. de Lemos, MD, of UT Southwestern Medical Center ^[1].

Limitations include the use of a subset of the larger trial, blood pressure measured at only two time points, nighttime readings taken once per hour, and no measurement of changes in food intake or 24-hour urine sodium excretion ^[1][2].

Tirzepatide is sold as Mounjaro for type 2 diabetes and as Zepbound for chronic weight management, approved by the FDA in November 2023 ^[1][2]. SURMOUNT-1 was supported by Eli Lilly ^[2].

Why it matters for patients

High blood pressure is common among adults with obesity, and this substudy suggests a weight-loss drug can move a reading that doctors track closely. The reduction at 10 mg, about 10.6 mmHg of systolic pressure, is a size the researchers compared to conventional blood pressure drugs ^[1][2].

The study does not show that tirzepatide prevents heart attacks, strokes or other cardiovascular events; those outcomes were not reported in this analysis. It also cannot separate the drug's own effects from the effects of losing weight, and de Lemos said that question remains open ^[1][2]. Participants started with blood pressure already below 140/90 mmHg, so results may not apply to people with higher readings — that has not been reported. Anyone prescribed either medicine still needs blood pressure to be monitored by a clinician, and the substudy did not test replacing blood pressure medication with tirzepatide.

What happens next

No timeline has been reported for the mechanistic studies de Lemos said are needed to determine whether the blood pressure lowering is fully explained by weight loss or involves other effects of the drug ^[2]. The substudy was published in Hypertension on February 2, 2024, and the American Heart Association highlighted it on February 5, 2024 ^[1].