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Zepbound achieved additional 6.7% weight loss following a 36-week open-label lead-in period, for a total mean weight loss of 26.0% from study entry over 88 weeks

INDIANAPOLIS, Dec. 11, 2023. Detailed results from SURMOUNT-4, which showed Zepbound (tirzepatide) injection achieved superior mean percent change in body weight compared to placebo in adults with obesity or overweight with weight-related comorbidities, excluding type 2 diabetes, were published in The Journal of the American Medical Association (JAMA). Zepbound met the primary endpoint of mean percent change in body weight, and all key secondary endpoints for both estimands i, ii, compared to placebo 52 weeks after randomization.

Study Design

SURMOUNT-4, a phase 3 study evaluating the safety and efficacy of Zepbound compared to placebo, had two periods.

SURMOUNT-4 utilized a maximum tolerated dose of 10 mg or 15 mg once-weekly. The starting dose of 2.5 mg Zepbound was increased by 2.5 mg every four weeks until maximum tolerated dose was achieved. Participants who tolerated 15 mg continued on 15 mg as their maximum tolerated dose. Participants who tolerated 10 mg but did not tolerate 15 mg continued on 10 mg as their maximum tolerated dose.

"Patients, providers and the public do not always understand obesity is a chronic disease that often requires ongoing treatment, which can mean that treatment is stopped once weight goals are met," said Jeff Emmick, MD, Ph.D., senior vice president, product development, Lilly. "However, studies like SURMOUNT-4 show that continued therapy can help people living with obesity maintain their weight loss."

The overall safety profile of tirzepatide in SURMOUNT-4 was similar to previously reported SURMOUNT and SURPASS trials. The most commonly reported adverse events in SURMOUNT-4 were gastrointestinal-related and generally mild to moderate in severity. During the Zepbound lead-in treatment period, the most frequent adverse events were nausea (35.5%), diarrhea (21.1%), constipation (20.7%) and vomiting (16.3%). During the double-blind period, the most frequent adverse events for Zepbound and placebo, respectively, were diarrhea (10.7% vs 4.8%), nausea (8.1% vs 2.7%), vomiting (5.7% vs 1.2%), COVID-19 (14.0% vs 14.9%) and upper respiratory infection (2.4% vs 5.4%). Treatment discontinuation due to an adverse event occurred in 7.0% of enrolled participants during the 36-week open-label lead-in treatment period, mainly due to gastrointestinal events. After the open-label lead-in period, treatment discontinuation rates due to adverse events were 1.8% (Zepbound) and 0.9% (placebo).

About SURMOUNT-4 and the SURMOUNT clinical trial program1

SURMOUNT-4 (NCT04660643) was a multi-center, randomized, double-blind, parallel, placebo-controlled trial comparing the efficacy and safety of tirzepatide to placebo in adults with obesity or overweight with weight-related comorbidities, excluding type 2 diabetes. The trial had two periods in which treatment was given as an adjunct to a reduced calorie diet and increased physical activity: a 36-week open-label lead-in period in which all participants took tirzepatide, and a subsequent 52-week double-blind treatment period in which participants were randomized to either continue on tirzepatide or switch to placebo, in addition to increased physical activity and reduced-calorie diet. The trial enrolled 783 participants across the U.S., including Puerto Rico, Argentina, Brazil and Taiwan into the open-label lead-in period and 670 participants were randomized in a 1:1 ratio in the 52-week double-blind treatment period to receive tirzepatide or placebo. The primary objective of the study was to demonstrate that tirzepatide is superior in percent change in body weight from randomization at 36 weeks to 88 weeks compared to placebo.

The SURMOUNT phase 3 global clinical development program for tirzepatide in chronic weight management began in late 2019 and has enrolled more than 5,000 people with obesity or overweight across six registration studies, four of which are global studies. SURMOUNT-1 and SURMOUNT-2 were submitted to the FDA and demonstrated tirzepatide significantly reduced body weight compared with placebo in people living with obesity or overweight, with or without type 2 diabetes through 72 weeks.

Topline data for SURMOUNT-3 and SURMOUNT-4 were announced on July 27, 2023; results for SURMOUNT-3 were presented in October at ObesityWeek 2023 and simultaneously published in Nature Medicine.

About Zepbound (tirzepatide) injection2
Zepbound (tirzepatide) injection is FDA-approved as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with obesity (BMI ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) with at least one weight-related comorbid condition. Zepbound is the first and only FDA-approved obesity treatment that activates both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) hormone receptors.

About Lilly

Lilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer's disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable.

i The efficacy estimand represents efficacy prior to discontinuation of study drug.
ii The treatment-regimen estimand represents the estimated average treatment effect regardless of treatment discontinuation.

Lilly Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Zepbound (tirzepatide) as a treatment for adults with obesity or overweight and reflects Lilly's current belief and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there can be no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with the results to date, that Zepbound will receive additional regulatory approvals, that Zepbound will be commercially successful or that we will meet anticipated timelines for its commercialization. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

References

  1. le Roux, C., Zhang, S., Aronne, L. et. al. Tirzepatide for the Treatment of Obesity: Rationale and Design of the SURMOUNT Clinical Development Program 2022 Obesity doi: 10.1002/oby.23612
  2. Zepbound. Prescribing Information. Lilly USA, LLC.

SOURCE Eli Lilly and Company

Posted: December 2023

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