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Tirzepatide delivers substantial, sustained reductions in body weight in SURMOUNT-1 obesity trial


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Ania M Jastreboff, MD, PhD
Ania M. Jastreboff, MD, PhD

Tirzepatide—a novel, once-weekly, dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist—provided substantial and sustained reductions in body weight in people living with obesity in the SURMOUNT-1 trial, according to results presented for the first time on Saturday, June 4, at the Scientific Sessions. SURMOUNT-1 is the first phase 3 obesity trial of tirzepatide.

The session, SURMOUNT-1—Results of the First Phase 3 Obesity Trial with the Novel GIP/GLP-1 Receptor Agonist Tirzepatide, was livestreamed and can be viewed on-demand by registered meeting attendees at If you haven’t registered for the 82nd Scientific Sessions, register today to access the valuable meeting content.

During the two-hour presentation, a panel of study authors described the study design and objectives, main results of the trial, and their implications for the present and future of obesity treatment.

The study enrolled 2,539 participants who were obese or overweight with at least one weight-related condition and who do not have diabetes. Participants were randomized to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Co-primary endpoints were the percentage change in weight from baseline and a weight reduction of 5% or more.

Sriram Machineni, MD
Sriram Machineni, MD

“All three doses of tirzepatide demonstrated substantial, clinically meaningful, and sustained body weight reduction compared to placebo,” said Ania M. Jastreboff, MD, PhD, Associate Professor at the Yale School of Medicine, Director of Weight Management and Obesity Prevention at the Yale Stress Center, and Co-director of the Yale Center for Weight Management.

Dr. Jastreboff presented the efficacy results from the study. She reported that, at 72 weeks, participants who received the 15 mg dose of tirzepatide achieved 20.9% weight reduction on average, while those on the 10 mg dose achieved an average 19.5% weight reduction, and the 5 mg group demonstrated 15% average weight reduction.

“Importantly, the weight reduction in all groups was sustained over the 72 weeks of treatment and all pre-specified cardiometabolic measures improved with tirzepatide,” Dr. Jastreboff said.

Sriram Machineni, MD, Assistant Professor of Medicine at the University of North Carolina and Director of the UNC Medical Weight Program, reviewed safety and tolerability findings from the study.

Louis J. Aronne, M.D.
Louis J. Aronne, M.D.

“The tolerability and safety profile of tirzepatide was consistent with other injectable incretin-based therapies for treating obesity,” he said. “Transient, mostly mild to moderate gastrointestinal events were the most frequently reported adverse events, occurring primarily during the dose-escalation period.”

There were four positively adjudicated cases of pancreatitis evenly distributed across the treatment groups, Dr. Machineni said.

“Cholecystitis was reported more frequently in the tirzepatide groups compared to the placebo group, which is consistent with previous reports for injectable incretin-based agents in obesity trials,” he added.

The findings from SURMOUNT-1 indicate that tirzepatide may be a potential therapeutic option for individuals living with obesity, said Louis J. Aronne, MD, the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medical College.

“Poor understanding of obesity, lesser efficacy, and concerns about safety and side effects have prevented wide adoption of anti-obesity medications (AOM),” Dr. Aronne said. “These findings show that it can be done—more weight loss can be achieved by hitting additional targets. There is a bright future for obesity treatment and AOM development.”