People who start treatment with Mounjaro or Zepbound begin with a 2.5-milligram dose, gradually increasing the dosage over time. Preliminary trial data indicates that adults with prediabetes who took tirzepatide, the active ingredient in both Zepbound and Mounjaro, had a 94 percent lower likelihood of developing type 2 diabetes compared to those on a placebo.
Key Findings:
- A new three-year study revealed that tirzepatide significantly reduced the risk of prediabetes advancing to diabetes by 94 percent in individuals who were overweight or obese, when compared with placebo results.
- Participants taking tirzepatide experienced a notable weight loss, ranging between 15 and 23 percent of their body weight.
- However, when the treatment was discontinued, some individuals began to regain weight, and a portion of them eventually developed diabetes.
Tirzepatide and Diabetes Prevention: An In-Depth Look
People who are overweight or obese and have prediabetes may significantly reduce their risk of progressing to full-blown type 2 diabetes when they take medications like Mounjaro or Zepbound. This finding comes from preliminary study results recently released by Eli Lilly, the pharmaceutical company that manufactures both drugs. These medications contain the active ingredient tirzepatide, which has shown promise in managing weight and blood sugar levels, two key factors in diabetes prevention.
The Study
In a randomized trial, researchers assigned 1,032 adults with prediabetes who were also overweight or obese to either take a placebo or one of three doses of tirzepatide. The participants were followed for about three years to monitor their progression from prediabetes to type 2 diabetes. The results were significant: people who took tirzepatide were 94 percent less likely to develop type 2 diabetes compared to those who received the placebo. According to Eli Lilly, this study underscores the potential of tirzepatide as a powerful intervention for diabetes prevention in high-risk populations.
Weight Loss: A Critical Factor
One of the most notable outcomes of the study was the substantial weight loss experienced by those taking tirzepatide. Participants who took the highest doses, 10 milligrams (mg) or 15 mg weekly, saw their body weight decrease by an average of 20 to 23 percent, respectively, compared to only a 2 percent decrease in the placebo group. Those on the lower 5 mg dose also lost more than 15 percent of their body weight, though this was not considered statistically significant.
Adam Gilden, MD, an associate professor and associate director of the weight management and wellness clinic at the University of Colorado School of Medicine, remarked on the impressive results. “These are excellent weight loss results at all doses,” he said, emphasizing how such outcomes align with what experts have seen in other weight management interventions.
Weight Gain After Stopping Tirzepatide
While the study highlighted the drug’s efficacy in both weight loss and diabetes prevention, the long-term sustainability of these benefits remains a concern. Participants were followed for an additional 17 weeks after stopping tirzepatide, and during this time, many began to regain the weight they had lost. Additionally, some individuals progressed to type 2 diabetes after discontinuing the medication. Although Eli Lilly did not disclose the exact amount of weight regained or how many people developed diabetes, these findings suggest that tirzepatide’s effects may not be permanent once treatment is halted.
Dr. Gilden commented on this challenge, stating, “It confirms what we know about anti-obesity medications, which is that the course of treatment is indefinite. These results tell us specifically that even after three years of treatment, people start to regain weight if medication is discontinued.”
Side Effects and Risks
The study also reported some adverse effects, most of which were related to gastrointestinal issues. Common side effects included diarrhea, nausea, constipation, and vomiting, which were generally mild to moderate in severity. These side effects are consistent with what has been observed in other trials involving GLP-1 receptor agonists, a class of drugs to which tirzepatide belongs.
Weight Loss Comparable to Other Studies
These results are in line with previous studies that have examined the effects of tirzepatide on weight loss. For instance, in a 72-week study involving individuals who were overweight or obese but did not have diabetes, participants who took tirzepatide and made intensive lifestyle changes saw their body weight decrease by an average of 27 percent, or more than 60 pounds. In another study that focused primarily on people with obesity, participants taking the highest dose of tirzepatide (15 mg) lost nearly 21 percent of their body weight.
According to Clifford Rosen, MD, a senior scientist at the MaineHealth Institute for Research and a professor at Tufts University School of Medicine, the dramatic weight loss seen in these studies likely explains the drug’s ability to significantly reduce the risk of type 2 diabetes. “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 explained. “Depending on the side effects, the optimal dose could be as high as 15 mg.”
Unanswered Questions About Tirzepatide
Tirzepatide represents a new class of drugs that target two hormones—glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)—both of which play critical roles in regulating blood sugar levels and signaling satiety (fullness) from the gut to the brain. It is marketed under the names Mounjaro for type 2 diabetes treatment and Zepbound for weight loss. While the study results are promising, some experts remain cautious about using tirzepatide purely for diabetes prevention.
“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 in Boston. “It is difficult to know if it was preventing diabetes or treating diabetes when it occurred.”
Dr. Hamdy pointed out the need for more comprehensive long-term studies to assess tirzepatide’s cost-effectiveness and durability. “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,” he said. This information would help determine whether tirzepatide can be a sustainable and affordable solution for diabetes prevention in the long run.
Potential Risks of Rapid Weight Loss
Another concern raised by experts is the impact of rapid weight loss on lean muscle mass and bone health. Dr. Rosen noted that while significant weight loss can be beneficial, it may also lead to reductions in muscle and bone mass, which could increase the risk of frailty, falls, and fractures over time. “We have no long-term data on changes in muscle and bone mass to determine optimal dosing that would balance any [negative] effects,” Dr. Rosen cautioned.
Conclusion
Tirzepatide shows great promise as a tool for weight management and diabetes prevention, particularly for individuals who are overweight or obese. However, as the study results suggest, its benefits may be temporary if the medication is discontinued. Additionally, more research is needed to address lingering questions about its long-term efficacy, cost-effectiveness, and potential side effects. Until these issues are resolved, experts like Dr. Hamdy urge caution in using tirzepatide solely for diabetes prevention, particularly in populations that may be more vulnerable to its risks.
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