GIP/GLP-1 Receptor Agonist Slashes Body Weight by More Than 20%

Tirzepatide, an investigational glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, helped people with overweight or obesity lose significant weight, Eli Lilly announced.

In the 72-week, phase III SURMOUNT-1 clinical trial, people taking 15 mg of the once-weekly injectable lost on average 22.5% of body weight — representing a mean loss of 52 lb (24 kg).

“Tirzepatide delivered impressive body weight reductions in SURMOUNT-1, which could represent an important step forward for helping the patient and physician partnership treat this complex disease,” said study investigator Louis J. Aronne, MD, of Weill Cornell Medicine in New York City, in a statement.

The trial also assessed two lower doses of tirzepatide, both of which were also effective. Adults taking 5 mg saw average weight reductions of 16.0% (35 lb, or 16 kg) and those taking 10 mg saw a loss of 21.4% (49 lb, or 22 kg) from the average baseline body weight of 231 lb (105 kg).

The trial also met its other co-primary endpoint, with more adults on tirzepatide achieving at least a 5% body weight reduction:

• 85% on 5 mg
• 89% on 10 mg
• 91% on 15 mg
• 35% on placebo

Likewise, 55% and 63% of people on 10 mg and 15 mg of tirzepatide, respectively, achieved at least a 20% body weight reduction (a key secondary endpoint) compared with 3.1% of those on placebo. A total of 32% of participants on 5 mg of tirzepatide also achieved this weight loss, but it was not controlled for type 1 error.

“Obesity is a chronic disease that often does not receive the same standard of care as other conditions, despite its impact on physical, psychological and metabolic health, which can include increased risk of hypertension, heart disease, cancer and decreased survival,” said Aronne in the statement.

SURMOUNT-1 included 2,539 adults with overweight or obesity who had at least one other comorbidity — hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease — but were free of type 2 diabetes. Tirzepatide was added to a reduced-calorie diet and increased physical activity regimen.

Individuals with prediabetes were allowed at enrollment and will remain enrolled for additional 104 weeks beyond the 72 weeks of the main trial to assess the impact on body weight and any possible differences in the progression to type 2 diabetes versus placebo.

The global, multicenter trial enrolled participants from the U.S., Argentina, Brazil, China, India, Japan, Mexico, Russia, and Taiwan.

Tirzepatide was initiated at a dose of 2.5 mg once-weekly and subsequently increased step-wise at 4-week intervals to the final randomized maintenance dose of 5 mg, 10 mg, or 15 mg.

Similar to other GLP-1 receptor agonist agents, the most common adverse events reported were gastrointestinal-related and occurred more often at higher doses. The most commonly reported were nausea (24.6% for 5 mg, 33.3% for 10 mg, 31.0% for 15 mg), diarrhea (18.7%, 21.2%, 23.0%), vomiting (8.3%, 10.7%, 12.2%), and constipation (16.8%, 17.1%, 11.7%).

The agent has already been well-studied in a population with type 2 diabetes, even showing a superior drop in hemoglobin A1c over 40 weeks versus the injectable GLP-1 receptor agonist semaglutide (Ozempic) in the SURPASS-2 trial.

Semaglutide currently dominates the weight-loss market, after it was approved at a higher dose for chronic weight management than for its type 2 diabetes indication — making it the first drug approved for this indication since 2014.