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SURMOUNT-2 shows weight loss, A1C reduction in participants with type 2 diabetes


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W. Timothy Garvey, MD, MACE
W. Timothy Garvey, MD, MACE

The SURMOUNT-2 trial of tirzepatide in individuals with obesity or overweight and type 2 diabetes showed a mean 15.7% reduction of body weight and a 5.94% reduction in A1C for the 15 mg dose at 72 weeks. That compares to a 20.9% weight loss in SURMOUNT-1 in individuals with obesity or overweight but not type 2 diabetes, a difference seen in trials of semaglutide and other agents with activity in both weight reduction and glycemic control.

“Patients with obesity and diabetes lose less weight than patients with obesity alone,” said W. Timothy Garvey, MD, MACE, Professor of Nutrition Sciences at the University of Alabama at Birmingham (UAB) and Director of the UAB Diabetes Research Center. “At the same time, about 90% of patients with type 2 diabetes have overweight or obesity. Patients with obesity and type 2 diabetes have two diseases, and both diseases should be treated effectively.”

SURMOUNT-2 data were presented in SURMOUNT 2 Trial Results and Potential Role of Tirzepatide in Treating Obesity in Type 2 Diabetes and published simultaneously in The Lancet. The session can be viewed on-demand by registered meeting participants at If you haven’t registered for the 83rd Scientific Sessions, register today to access the valuable meeting content through August 28.

Matthias H. Tschöp, MD, PhD
Matthias H. Tschöp, MD, PhD

Tirzepatide is the first dual incretin inhibitor, targeting both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. Development began two decades ago with a project to develop single-molecule, multi-receptor drugs to produce up to 30% weight loss in obesity.

A1C benefits were an unexpected bonus, said Matthias H. Tschöp, MD, PhD, CEO at Helmholtz Munich and the Alexander von Humboldt Professor at the Technical University of Munich, Germany. The U.S. Food and Drug Administration (FDA) approved the agent in 2022 for glycemic control in adults with type 2 diabetes while noting weight-loss benefits.

More than 80% of SURMOUNT-2 participants achieved equal to or greater than 5% weight loss from baseline, more than 45% achieved equal to or greater than 15%, more than 30% achieved equal to or greater than 20%, and more than 15% achieved equal to or greater than 25%.

“Greater than a 20% weight loss is something I once thought to be unattainable,” Dr. Tschöp said.

Juan Pablo Frias, MD
Juan Pablo Frias, MD

SURMOUNT-2 randomized a total of 938 patients with type 2 diabetes and with a BMI of equal to or greater than 27 to placebo (315 patients), 10 mg weekly of tirzepatide (312 patients) or 15 mg weekly (311 patients). Patients in the active arm started on 5 mg a week and increased to the maximum dose by week 20.

The mean age of patients was 54 years, and half were female. The trial was conducted across 77 sites in seven countries.

Primary objectives were to demonstrate that 10 mg and/or 15 mg weekly doses of tirzepatide were superior to the placebo for weight reduction. Key secondary objectives included superiority for A1C reduction, change in waist circumference, changes in fasting lipids, and systolic blood pressure versus placebo. The trial met all primary and key secondary objectives.

Naveed Sattar, MD, PhD
Naveed Sattar, MD, PhD

Patients were followed for 72 weeks to meet regulatory requirements for a minimum of 52 weeks of follow-up for those with both type 2 diabetes and obesity or overweight, said Juan Pablo Frias, MD, Medical Director and Principal Investigator, Velocity Clinical Research.

“We conducted this trial during [the COVID-19 pandemic] and had a completion rate of better than 90%,” Dr. Frias said.

There were no unexpected safety signals, reported Naveed Sattar, MD, PhD, Professor of Metabolic Medicine, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom. Treatment-emergent adverse events and serious adverse events were similar across all three arms. There were no reports of serious hypoglycemia, and less severe hypoglycemia was more common in those taking sulfonylureas at baseline.

The most common adverse events were gastrointestinal, nausea, diarrhea, and vomiting. Most were mild to moderate, and all were more common in the active treatment arms.