Tirzepatide Yields Significant Weight Loss in Patients with Obesity in SURMOUNT-1

Data show the mean percentage change in weight at week 72 was -15.0% with 5-mg weekly doses of tirzepatide, -19.5% with 10-mg, and -20.9% with 15-mg dose, compared to -3.1% with placebo.

New findings from the 72-week SURMOUNT–1 trial suggest that the 5 mg, 10 mg, and 15 mg dose of once-weekly tirzepatide had substantial reductions in body weight in individuals with obesity.

Data show the participants had average weight reductions of 19.5% and 20.9% with 10-mg and 15-mg doses of tirzepatide, respectively, with up to 22.5% reduction with the latter dose.

“This is an unusually substantial degree of weight reduction in response to an anti obesity medication as compared with findings reported in other phase 3 clinical trials,” wrote study author Ania M. Jastreboff, MD, PhD, Yale University School of Medicine. “Given that tirzepatide is both a GIP receptor and GLP-1 receptor agonist, we speculate that there may be additive benefit in targeting multiple endogenous nutrient-stimulated hormone pathways that have been implicated in energy homeostasis.”

These late-breaking findings were presented at the American Diabetes Association (ADA) 2022 Scientific Sessions.

Previous research theorized that a molecule that combines both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GiP) may be more efficacious in reducing weight.

The phase 3 multicenter, double-blind, randomized, placebo-controlled SURMOUNT-1 trial was conducted at 119 sites in 9 countries. Patients were included if they were ≥18 years, with a body mass index (BMI) of ≥30, or a BMI of ≥27 and at least one weight-related complication and reported ≥1 unsuccessful dietary effort to lose weight. Key exclusion criteria included diabetes, a change in body weight ≥90 days before screening, surgical treatment for obesity, and treatment with weight loss medication.

Following a 2-week screening period, the patients were randomized in a 1:1:1:1 ratio to tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or placebo administered subcutaneously once-weekly for 72 weeks. The coprimary end points were considered the percentage change in body weight from baseline to week 72 and a weight reduction of ≥5% at week 72. Key secondary end points included weight reductions of ≥10%, ≥15%, and ≥20% at week 72.

From a total of 2539 participants, 86.0% completed the primary trial treatment period and 81.9% adhered to either the treatment or placebo as per their assignment. Investigators noted the mean age of the participants was 44.9 years, most were female (67.5%) and White (70.6%), and 94.5% of individuals had a BMI ≥30.

Data show the mean percentage change in weight at week 72 was -15.0% (95% confidence interval [CI], -15.9 to -14.2) with 5-mg weekly doses of tirzepatide, -19.5% (95% CI, -20.4 to -18.5) with 10-mg doses, and -20.9% (95% CI, -21.8 to 19.9) with 15-mg doses. Meanwhile, the mean percentage change was -3.1% (95% CI, -4.3 to -1.9) with placebo (P <.001 for all comparisons with placebo).

Then, regarding the treatment-regimen estimand, investigators observed 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) of individuals in the 5-mg, 10-mg, and 15-mg tirzepatide groups, respectively, had a body weight reduction of ≥5% at 72 weeks.

In comparison, 35% (95% CI, 30 - 39) of those in the placebo group met this end point (P <.001 for all comparisons with placebo). Investigators additionally noted 95.3% of participants with prediabetes at baseline in the tirzepatide cohort reverted to normoglycemia at week 72, compared with 61.9% of the placebo group. All key secondary reported treatment with tirzepatide had an association with greater improvement from baseline than placebo.

For safety outcomes, investigators found 78.9 to 81.8% of participants treated with tirzepatide reported ≥1 adverse event that emerged during the treatment period, compared to 72.0% in the placebo group. Most events reported were considered gastrointestinal in nature. They caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively.

“With substantial observed weight reductions at all three doses, tirzepatide may serve as an important tool in the medical management of obesity,” Jastreboff concluded.

The study, “Tirzepatide Once Weekly for the Treatment of Obesity,” was published in The New England Journal of Medicine.