Announced on November 8, 2023, the approval of tirzepatide(Zepbound) was awarded to Eli Lilly and Company and represents the first chronic weight management approval for a dual GLP-1/GIP receptor agonist.
The US Food and Drug Administration has approved tirzepatide (Zepbound) for use in chronic weight management.
Announced by the agency on November 08, 2023, the approval indicates tirzepatide, which is the first dual GLP-1/GIP agonist to receive such an approval, as an adjunct for chronic weight management in adults with obesity or overweight with at least 1 weight-related condition in addition to a reduced calorie diet and increased physical activity. Awarded to Eli Lilly and Company, which expects to be available in the US by the end of the year at a list price of $1,059.87, the approval is based on results of the SURMOUNT-1 and SURMOUNT-2 trials.
“Obesity and overweight are serious conditions that can be associated with some of the leading causes of death such as heart disease, stroke and diabetes,” said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research.1 “In light of increasing rates of both obesity and overweight in the United States, today’s approval addresses an unmet medical need.”
The recipient of Priority Review and Fast Track designations for this indication, the approval comes just more than a year after the agent made history as the first GLP-1/GIP agonist to receive an indication as an adjunct for improving glucose control in people with type 2 diabetes. In their release, Eli Lilly and Company purported their expected list price as about 20% lower than semaglutide 2.4 mg injection.
A phase 3 double-blind, randomized, controlled trial, SURMOUNT-1 enrolled 2539 patients with a BMI of 30 kg/m2 or greater or 27 kg/m2 plus at least 1 weight-related complication, excluding diabetes. The 2539-patient cohort had a mean age of 44.9 (Standard deviation [SD], 12.5) years, mean body weight was 104.8 kg, the mean BMI was 38.0 kg/m2, and 94.5% of participants had a BMI of 30 kg/m2 or greater at baseline.3
These patients were randomized in a 1:1:1:1 ratio to receive tirzepatide in 5 mg, 10 mg, or 15 mg doses or placebo therapy for 72 weeks, including a 20-week dose-escalation period. The trial had a pair of coprimary endpoints, which were the percentage change in weight from baseline and a weight reduction of 5% or more.3
When assessing percentage change in weight, results suggested the mean percentage change in weight at week 72 was −15.0% (95% CI, −15.9 to −14.2) with tirzepatide 5 mg, −19.5% (95% CI, −20.4 to −18.5) with tirzepatide 10 mg, and −20.9% (95% CI, −21.8 to −19.9) with tirzepatide 15 mg compared to −3.1% (95% CI, −4.3 to −1.9) with placebo (P <.001 for all).3
Results indicated a weight reduction of 5% or more was achieved by 85% (95% CI, 82 to 89) with tirzepatide 5 mg, 89% (95% CI, 86 to 92) with tirzepatide 10 mg, and 91% (95% CI, 88 to 94) with tirzepatide 15 mg compared to 35% (95% CI, 30 to 39) with placebo (P <.001 for all). In the trial, 50% (95% CI, 46 to 54) of the tirzepatide 10 mg arm and 57% (95% CI, 53 to 61) of the tirzepatide 15 mg arm had a reduction in body weight of 20% or more. Among those in the placebo arm, this degree of weight loss was achieved by just 3% (95% CI, 1 to 5) of those receiving placebo.3
A double-blind, placebo-controlled trial, SURMOUNT-2 enrolled a population of 938 participants who underwent randomization in a 1:1:1 ratio to placebo therapy or tirzepatide 10 or 15 mg. The trial cohort had a mean age of a mean age of 54.2 (SD, 10.6) years, 50.7% were female, and 75.7% were White. At baseline, the cohort had a mean bodyweight of 100.7 kg (SD, 21.1), BMI 36.1 kg/m2 (SD, 6.6), and HbA1c 8.02% (SD, 0.89; 64.1 mmol/mol [SD, 9.7]).4
The trial was designed with a pair of coprimary endpoints, which were the percent change from randomization in body weight and percentage of participants who achieved body weight reduction from randomization of at least 5%.4
Upon analysis, results suggested the least-squares mean change in body weight at week 72 with tirzepatide 10 mg and 15 mg was -12.8% (SE, 0.6) and -14.7% (SE, 0.5), respectively, compared to -3.2% (SE, 0.5) with placebo therapy, which correlated with an estimated treatment differences relative to placebo of -9.6 percentage points (95% CI, –11.1 to -8.1) with tirzepatide 10 mg and -11.6 percentage points (-13.0 to -10.1) with tirzepatide 15 mg (all P < .0001). Analysis of the second coprimary endpoint suggested 79-83% of patients randomized to tirzepatide achieved a body weight reduction of 5% or greater compared to 32% of those receiving placebo therapy.4
"Obesity is a chronic disease that can result in serious health complications, including heart disease, stroke and diabetes. Despite our knowledge of obesity as a treatable, chronic disease, people living with obesity still face many challenges in their health and weight management journey," said Joe Nadglowski, president and chief executive officer of the Obesity Action Coalition.2 "New treatment options bring hope to the many people with obesity who struggle with this disease and are seeking better options for weight management."
Check out this video with Timothy Garvey, MD, giving a breakdown of SURMOUNT-2 data and how it complements SURMOUNT-1 in an interview from ADA 2023.