Tirzepatide (Zepbound) demonstrated superiority compared to semaglutide (Wegovy) across the primary end point and 5 key secondary end points.
Full results from the SURMOUNT-5 (
"In the SURMOUNT-5 trial, Zepbound demonstrated a significantly higher magnitude of weight reduction compared to Wegovy across all comparisons," Leonard Glass, MD, FACE, senior vice president of global medical affairs at Eli Lilly, said in a news release.1 "These data confirm Zepbound as a leading treatment option for people living with obesity and equip healthcare providers with critical insights to make well-informed treatment decisions as part of a comprehensive obesity care plan."
The investigators aimed to compare the glucagon-like peptide (GLP-1) and gastric inhibitory polypeptide dual agonist, tirzepatide, with the GLP-1 mono agonist, semaglutide. Patients included had a body mass index of 40 kg/m2 or greater or 27 kg/m2 with at least 1 weight-related comorbidity. Patients with diabetes were excluded.
The primary outcome included percent change from baseline body weight to week 72. Secondary end points included percentage of participants who achieved 10% or greater, 15% or greater, 20% or greater, and 25% or greater body weight reductions; change from baseline in waist circumference; change from baseline in body mass index; and percent change from baseline in body weight with tirzepatide 15 mg and semaglutide 2.4 mg.3
Trial Name: A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities (SURMOUNT-5)
ClinicalTrials.gov ID: NCT05822830
Sponsor: Eli Lilly and Company
Completion Date: December 11, 2024
Investigators included 750 patients between April 21, 2023, and November 13, 2024, with 85% of patients completing treatment and 80.2% completing the 72 weeks of trial. They found that the mean percentage change in body weight with tirzepatide was a reduction of 20.2% compared with a decrease of 13.7% for semaglutide, equating to a body weight change of approximately 22.8 kg and 15 kg, respectively. Further, patients treated with tirzepatide were 1.3, 1.6, 1.8, and 2 times more likely to have at least 10%, 15%, 20%, and 25% weight loss, respectively.2
For waist circumference, patients treated with tirzepatide had a reduction of 18.4 cm compared with 13 cm for semaglutide. As for blood pressure, both systolic and diastolic had improvements with both treatments. Hemoglobin, fasting serum glucose, and lipid levels improved with both treatments. Approximately 76.7% of patients treated with tirzepatide and 79% treated with semaglutide experienced at least 1 adverse event (AE). The most frequently reported AEs included gastrointestinal events, such as nausea, constipation, diarrhea, and vomiting. These events were also the most likely to lead to treatment discontinuation at 5.6% in the tirzepatide group and 2.7% in the semaglutide group.2
Serious AEs were reported in 31 patients, with 4.8% from the tirzepatide group and 3.5% in the semaglutide group. There were no major cardiovascular events, deaths, cases of medullary thyroid cancer, or cases of pancreatic cancer reported.1
“With both treatments in our trial, as weight reduction increased, greater improvements occurred in cardiometabolic risk factors, including blood pressure, glycemia, and lipid levels, which is consistent with the findings in previous reports,” the study authors said. “The evaluation of the effect of greater weight reduction on decreases in cardiometabolic risk factors may translate to improved shared decision making by assisting with the selection of treatment goals.”
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