Zepbound Reversed Prediabetes, Prevented Progression to Type 2 for Nearly Everyone, Study Shows

Lilly has shared complete results from SURMOUNT-1, a trial that studied the use of tirzepatide (a medication sold under the names Zepbound and Mounjaro) in patients who were overweight (defined as a BMI between 25-30) or patients with obesity, including those with and without prediabetes. Results were presented at the Annual Meeting of the Obesity Society and published in the New England Journal of Medicine.

The results are staggering: After more than three years, nearly 99% of all participants who took tirzepatide were able to prevent type 2 diabetes, and 94% of participants with prediabetes taking tirzepatide were able to reverse their prediabetes and return their glucose levels to normal. 

In addition, research showed that participants taking tirzepatide saw up to 23% body weight reduction, increased levels of HDL cholesterol, and reductions in waist circumference, blood pressure, and triglycerides throughout the study. 

These study results further underscore the long-term benefits of taking tirzepatide, which extends beyond the current FDA-approved uses for type 2 diabetes (Mounjaro) and weight loss (Zepbound).

SURMOUNT-1: A clinical trial studying tirzepatide

Study design

The SURMOUNT-1 study examined the impact three doses of tirzepatide (5, 10, and 15 mg) had on body weight when combined with a low-calorie diet and increased exercise in people with obesity or overweight who did not have diabetes. More than 2,500 subjects participated in the initial 72-week portion of the trial.

A subgroup who had prediabetes – about 41% of the participant group, or just over 1,000 people  – continued with the treatment for a total of 176 weeks and were evaluated using additional treatment outcome measures such as time to onset of type 2 diabetes and reversion to normal blood glucose levels.

History of SURMOUNT-1 key findings

In June 2022, the clinical trial’s researchers published results from the first 72 weeks of the 193-week study. This analysis, which followed roughly 2,400 participants living with overweight or obesity, reported that participants lost an average of 52 pounds (21% of their weight) on the highest dose of tirzepatide. The same analysis also reported that 95% of people with prediabetes who took tirzepatide reverted to normal glucose levels compared to 62% who were given a placebo. Participants also experienced improvements in their fasting glucose, A1C, blood pressure, waist circumference, and insulin levels.

In August 2024, researchers released a snapshot of results from the complete 193-week study, which included the 1,032-person subgroup with prediabetes. Tirzepatide reduced the risk of progression from prediabetes to diabetes by about 90% in people living with obesity or overweight. In addition, weight reduction ranged from 12% to 23%, depending on the dose of tirzepatide.

These 3-year full results now paint a clear picture that for people with prediabetes, tirzepatide can reverse prediabetes in many as well as prevent progression to type 2 in almost everyone. Over 176 weeks, only nine of the 762 participants given some dose of tirzepatide developed type 2 diabetes.

What these results mean for prediabetes

The full results of the SURMOUNT-1 study further reinforce the benefits of tirzepatide, and open the door for Lilly to seek FDA approval for use of the drug to prevent  type 2 diabetes. 

“The SURMOUNT-1 study of prevention of type 2 diabetes and prediabetes demonstrates exactly what would be predicted from the dietary studies of similar weight loss,” said Dr. Roy Taylor, professor of medicine and metabolism at the University of Newcastle School of Medicine in England. Taylor's research has shown that prediabetes and type 2 diabetes may be able to be reversed through diet and weight loss by addressing fat buildup in the liver and pancreas.

The study results are promising, he notes, with the caveat that tirzepatide and other drugs in the same class offer risks along with benefits and may not be suitable for everyone.

“Overall, this study provides good news, he said, “but how to use the powerful appetite suppressants in clinical practice requires careful consideration.”

Tirzepatide belongs to a class of medications known as incretins, some of which have been approved for treatment of several conditions from type 2 diabetes (Mounjaro) to weight loss (Zepbound). This has led to unprecedented consumer demand as well as global drug shortages.

A growing case for the use of certain incretins in prediabetes

The SURMOUNT-1 results also add to a growing body of evidence that suggest tirzepatide and certain other medications in the incretin drug class may have benefits beyond the treatment of type 2 diabetes, including preventing type 2 diabetes in people who were overweight or had obesity.

Earlier this summer, results of Novo Nordisk’s STEP-10 trial also showed a reduction in prediabetes progression to type 2 diabetes. The STEP-10 study found that a 2.4 mg injection of semaglutide (sold as Wegovy for weight loss) led to significant weight loss and a return to A1C levels of less than 5.7% when compared to a placebo. Following the success of STEP-10, Novo Nordisk will likely also submit a request for FDA approval for semaglutide to prevent progression from prediabetes to type 2 diabetes.

Further reading about the benefits of tirzepatide here:

• New Trial Studying Tirzepatide for Chronic Kidney Disease
• Zepbound (Tirzepatide) FDA-Approved for Chronic Weight Management
• Mounjaro Superior to Ozempic for Blood Glucose Control and Weight Loss
• Eli Lilly Launches Digital Pharmacy With Home Delivery Service

Photo credits: iStock (top, middle); Newcastle University (headshot).