Zepbound Almost Eliminates Diabetes Risk in Overweight People

This content originally appeared on Everyday Health. Republished with permission.

By Lisa Rapaport

Key Takeaways

Results from a new three-year study showed that tirzepatide reduced the risk of prediabetes progressing to diabetes by 94 percent compared with placebo for people who were overweight or had obesity.
People taking tirzepatide also lost between 15 and 23 percent of their body weight.
Once people stopped taking the drug, they began to regain weight and some of them did go on to develop diabetes.

People who are overweight or have obesity and have prediabetes may be less likely to develop full-blown diabetes when they take Mounjaro or Zepbound, according to preliminary study results released by drugmaker Eli Lilly.

For the study, researchers randomly assigned 1,032 adults with prediabetes who were also overweight or had obesity to take a placebo or one of three doses of tirzepatide, the active ingredient in Mounjaro and Zepbound, for about three years. Overall, people who took tirzepatide were 94 percent less likely to develop type 2 diabetes than those on placebo, Eli Lilly said in a statement.[1]

People on the two highest tirzepatide doses also experienced statistically significant weight loss, the company said. By the end of the study period, weight decreased by an average of about 20 percent for people taking 10 milligrams (mg) weekly of tirzepatide and by roughly 23 percent on average with a weekly 15 mg dose, compared with only about 2 percent for those on the placebo. People lost more than 15 percent of their weight on the 5 mg weekly dose, but the company didn’t describe this as statistically significant.

“These are excellent weight loss results at all doses,” says Adam Gilden, MD, an associate professor and associate director of the weight management and wellness clinic at the University of Colorado School of Medicine in Aurora, who was not involved in this trial.

The study also followed people for an additional 17 weeks after they stopped taking tirzepatide injections. During this time, participants started to regain some of the weight they had lost on the drug and some of them progressed to type 2 diabetes, Eli Lilly said. The company didn’t specify how much weight they regained or how many of them had their diabetes progress.

Weight Gain After Stopping Tirzepatide

Even so, these findings add to the evidence suggesting that these drugs may not have a lasting impact after people stop taking them, Dr. Gilden says.

“It confirms what we know about anti-obesity medications, which is that the course of treatment is indefinite,” Gilden says. “These results tell us specifically that even after three years of treatment, people start to regain weight if medication is discontinued.”

The most frequently reported adverse events were typically gastrointestinal-related and generally mild to moderate in severity, Eli Lilly said. The most common gastrointestinal side effects experienced by people on tirzepatide were diarrhea, nausea, constipation, and vomiting, the company said.

Weight Loss Results Similar to Those in Other Studies

These are just the latest study findings to demonstrate significant weight loss with tirzepatide. In one 72-week study of people who were overweight or had obesity who didn’t have diabetes, participants’ weight dropped by an average of about 27 percent, or by more than 60 pounds, when they took the drug and also made intensive lifestyle changes. In another 72-week study primarily on people with obesity, participants taking a 15-mg tirzepatide dose saw their weight decrease by almost 21 percent on average.

The dramatic weight loss seen with tirzepatide — especially at higher doses — most likely explains why it led to such a big reduction in the risk of type 2 diabetes in the new study, says Clifford Rosen, MD, a senior scientist at the MaineHealth Institute for Research and a professor at Tufts University School of Medicine in Boston, who was not involved in the current trial.

“Most likely the highest dose was associated with the greatest weight loss and hence will lead to less progression to type 2 diabetes,” Dr. Rosen says. “Depending on the side effects, the optimal dose could be as high as 15 mg.”

Unanswered Questions About Tirzepatide

Tirzepatide is the first drug in a new family of medicines that target two hormones — glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) — that are involved in maintaining healthy blood sugar levels and sending signals from the gut to the brain when people are full. It’s the main ingredient in Mounjaro, for type 2 diabetes, and Zepbound, for weight loss.

“Although the results are impressive, we don’t have to ignore that the study used a diabetes medication to prevent diabetes,” says Osama Hamdy, MD, PhD, medical director of the obesity clinical program and director of the inpatient diabetes program at the Joslin Diabetes Center and an associate professor at Harvard Medical School in Boston, who was not involved in this research.

“It is difficult to know if it was preventing diabetes or treating diabetes when it occurred,” Dr. Hamdy says. “It is important to know the rate of prevention at each dose, but more importantly to evaluate that effect after stopping medication for one year to calculate cost-effectiveness and durability of this intervention.”

Because of these unanswered questions, it’s too soon to use tirzepatide just for diabetes prevention, Hamdy says.

Rapid weight loss, like what’s been seen with tirzepatide, also has the potential to reduce lean muscle mass and bone mass, issues that can increase the risk of frailty, falls, and fractures over time, Rosen says.

“We have no long term data on changes in muscle and bone mass to determine optimal dosing that would balance any [negative] effect,” Rosen says.

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