Treatment with tirzepatide was associated with significant weight loss in obese and overweight adults, according to phase 3 data.
Tirzepatide is an investigational once-weekly, dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that integrates the actions of both incretins into a single molecule. GIP is believed to complement the effects of GLP-1 receptor agonists.
The multicenter, randomized, double-blind, parallel, placebo-controlled SURMOUNT-1 trial (ClinicalTrials.gov Identifier: NCT04184622) evaluated the efficacy and safety of tirzepatide as an adjunct to a reduced-calorie diet and increased physical activity in 2539 adults without type 2 diabetes who have obesity, or are overweight with at least 1 of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease. The mean baseline body weight of patients was 105kg.
Patients were randomly assigned 1:1:1:1 to receive either tirzepatide 5mg, 10mg, 15mg, or placebo subcutaneously once weekly for 72 weeks. The coprimary endpoints of the study were the percent change from baseline in body weight and the percentage of patients who achieved at least 5% body weight reduction at week 72.
The efficacy estimand results demonstrated that treatment with tirzepatide was associated with the following body weight reductions at week 72 vs placebo, respectively:
- Average body weight reductions: 16% (16kg on 5mg), 21.4% (22kg on 10mg), 22.5% (24kg on 15mg) vs 2.4% (2kg)
- Percentage of patients achieving at least 5% body weight reduction: 89% (5mg), 96% (10mg and 15mg) vs 28%
- Percentage of patients achieving at least 20% body weight reduction (key secondary endpoint): 32% (5mg, not controlled for type 1 error), 55% (10mg), 63% (15mg) vs 1.3%
For the treatment-regimen estimand, tirzepatide was associated with the following body weight reductions at week 72 vs placebo, respectively:
- Average body weight reductions: 15% (5mg), 19.5% (10mg), 20.9% (15mg) vs 3.1%
- Percentage of patients achieving at least 5% body weight reduction: 85% (5mg), 89% (10mg), 91% (15mg) vs 35%
- Percentage of patients achieving at least 20% body weight reduction: 30% (5mg; not controlled for type 1 error), 50% (10mg), 57% (15mg) vs 3.1%
The safety profile of tirzepatide was similar to other incretin-based therapies approved for the treatment of obesity. The most common adverse events reported were gastrointestinal-related (nausea, diarrhea, vomiting, constipation) and generally mild to moderate in severity.
Patients who were prediabetic at baseline will remain enrolled in the SURMOUNT-1 study for an additional 104 weeks of treatment to evaluate the impact of tirzepatide on body weight and potential difference in progression to type 2 diabetes. The Company will continue to evaluate study results, which will be presented at an upcoming medical meeting and submitted to a peer-reviewed journal.
“Tirzepatide is the first investigational medicine to deliver more than 20% weight loss on average in a phase 3 study, reinforcing our confidence in its potential to help people living with obesity,” said Jeff Emmick, MD, PhD, vice president, product development, Lilly. “We’re proud to research and develop potentially innovative treatments like tirzepatide, which helped nearly two thirds of participants on the highest dose reduce their body weight by at least 20% in SURMOUNT-1.”
Lilly’s tirzepatide delivered up to 22.5% weight loss in adults with obesity or overweight in SURMOUNT-1. News release. Eli Lilly and Company. Accessed April 28, 2022. https://www.prnewswire.com/news-releases/lillys-tirzepatide-delivered-up-to-22-5-weight-loss-in-adults-with-obesity-or-overweight-in-surmount-1–301534871.html