The first clinical trial comparing semaglutide and tirzepatide, two popular, injectable weight-loss drugs, has been published, examining their ability to reduce weight and waist circumference. And one clearly comes out on top.
Injectable GLP-1 receptor agonist drugs Wegovy (semaglutide) and Zepbound (tirzepatide) have revolutionized weight loss. But, strangely, no one has compared the two to determine which one is better at shedding the pounds. Until now.
A new study led by Weill Cornell Medicine in New York was the first to undertake a head-to-head comparison of the weight loss effectiveness of semaglutide and tirzepatide, and one of them clearly came out on top.
“Our study shows that treatment with tirzepatide was superior to semaglutide with respect to reduction in body weight and waist circumference,” said lead and corresponding author Louis Aronne, MD, a specialist in obesity medicine from Weill Cornell’s Comprehensive Weight Control Center.
While both drugs are GLP-1 receptor agonists, which means they mimic the hormone glucagon-like peptide-1 that regulates appetite and food intake, tirzepatide also acts on glucose-dependent insulinotropic polypeptide (GIP) receptors. As well as regulating the release of insulin in response to food, GIP receptors play a role in reducing appetite and enhancing feelings of fullness.
The phase 3b clinical trial recruited 751 adults with obesity but without type 2 diabetes. Participants were randomly assigned to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg), delivered by under-the-skin or subcutaneous injection once a week for 72 weeks. Participants were included if they had a body mass index (BMI) of 30 kg/m2 or more (that is, obese), or a BMI of 27 kg/m2 or more (overweight) plus at least one weight-related complication, such as high blood pressure, high cholesterol levels, obstructive sleep apnea, or heart disease. The study’s primary endpoint was the percentage change in weight from baseline to week 72. A secondary endpoint was a change in waist circumference over that time.
Participants taking tirzepatide experienced a mean weight reduction of 20.2% at 72 weeks, while those taking semaglutide reduced their weight by a mean of 13.7%. That means that weight loss attributable to tirzepatide was 47% higher than that attributable to semaglutide. The mean decrease in waist circumference for those on tirzepatide was 18.4 cm/7.2 in, and for those on semaglutide it was 13 cm/5.1 in – 42% higher for tirzepatide.
“Tirzepatide, while a single molecule, pharmacologically activates two metabolic receptors, GIP and GLP-1, which have both overlapping and non-overlapping expression and function,” Aronne said. “This dual agonism of tirzepatide may contribute to the higher weight reduction observed in the current study compared to semaglutide, a mono-agonist.”
The most common adverse events for both treatment groups were gastrointestinal, mostly mild to moderate in severity. They commonly occurred as the treatment dose was being increased.
The study had strengths, too. Particularly the study’s diversity, which included participants who identified as Black/African American (19%) and Hispanic/Latino (26%), two populations that are more affected by obesity compared with other racial and ethnic groups. However, it also had limitations. The most significant being that it was not a blinded study, meaning that participants knew the drug they were taking and its dose. However, the researchers said that their findings were consistent with those of previous blinded studies, increasing their generalizability.
“Our study shows that treatment with tirzepatide was superior to semaglutide with respect to reduction in body weight and waist circumference,” said Aronne.
The study, funded by Eli Lilly, was presented at this year's European Congress on Obesity (ECO) in Malaga, Spain, and published in The New England Journal of Medicine.
Source: European Association for the Study of Obesity (EASO)
