Study shows tirzepatide reduces diabetes risk by 90% in obese patients

Study shows tirzepatide reduces diabetes risk by 90% in obese patients

Tirzepatide, a new injectable weight-loss drug with the trade name Zepbound, reduced the risk of diabetes in patients with obesity and prediabetes by more than 90% over three years compared to placebo, according to results of a new study led by researchers at Weill Cornell Medicine, NewYork-Presbyterian, Yale School of Medicine and other institutions.

The study, published Nov. 13 in the New England Journal of Medicine, was a follow-up to one of the first Eli Lilly-sponsored tirzepatide trials, the 72-week SURMOUNT-1 trial, which supported FDA approval of the injectable drug for diabetes and later obesity. The new results show that after 176 weeks of treatment, only 1.3% of patients who were both obese and prediabetic and took the drug in one of three doses developed type 2 diabetes, compared to 13.3% of patients who took a placebo.

“These results show that type 2 diabetes can be prevented even in people who are on the verge of developing it by taking a drug that causes weight loss,” said study co-author Dr. Louis Aronne, Sanford I. Weill Metabolic Research Professor and director of the Comprehensive Weight Control Center, part of the Division of Endocrinology, Diabetes and Metabolism at Weill Cornell Medicine.

A portion of the study's patients were treated at Weill Cornell Medicine, where Dr. Aronne and colleagues have worked for decades to advance the concept of obesity - the leading cause of type 2 diabetes - as a treatable disease.

Tirzepatide is one of a broad new class of drugs that simulate nutrient-stimulated hormones and help patients significantly lose weight and improve blood sugar control. The drugs work, at least in part, by activating one or more receptors throughout the body, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptors on cells in the brain, pancreas and elsewhere. Tirzepatide activates both GLP-1 and GIP, resulting in greater weight loss and fewer side effects than older GLP-1 monopreparations. The overall effect of the drug is to promote a feeling of satiety or “fullness,” which reduces cravings for food and increases insulin secretion, thereby reducing blood sugar levels.

The SURMOUNT-1 trial initially found that patients with obesity who took tirzepatide for 72 weeks lost an average of 15 to 22.5% of their baseline weight, depending on the dose, and also experienced a significant average reduction in their glycated hemoglobin levels than A1c levels, a standard measure of blood sugar control. The new study focused on 1,032 of these patients who initially had obesity and prediabetes - a precursor to diabetes in which A1c levels are above normal but below the threshold for diabetes.

The study found that after 176 weeks, only 10 patients treated with tirzepatide developed diabetes, representing a risk reduction of about 93% compared to the placebo group. More than 90% of tirzepatide-treated patients had normal A1c values ​​at 176 weeks, compared to 59% of placebo-treated patients.

The process did not uncover any new safety issues; The most common gastrointestinal side effects, such as nausea and vomiting, decreased over the course of the study, suggesting that long-term use of tirzepatide is relatively tolerable. A follow-up analysis 17 weeks after cessation of treatment showed a slight increase in weight and a slight increase in A1c levels, which returned some patients to the prediabetes and diabetes ranges and underscores the likely need for chronic treatment.

The results suggest the drug could one day be the first approved treatment for prediabetes, Dr. Aronne, who is also an internist specializing in diabetes and obesity at NewYork-Presbyterian/Weill Cornell Medical Center.

“Think about the impact these types of weight loss medications can have on not only preventing diabetes, but also many other common diabetes-related complications such as heart disease, liver and kidney disease, sleep apnea, arthritis, and more.”

Dr. Louis Aronne, co-author of the study

Over time, treating obesity may become the first-line treatment and used more frequently than treating high blood pressure or cholesterol.

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