Prescribing Advice for GPs

Weight Gain After Tirzepatide

March 27, 2025 at 8:38 am | In Prescribing Extra - Drugs | Print | No Comments

The New England Journal of Medicine has recently published the results of a long term study investigating the safety and efficacy of tirzepatide in reducing weight and delaying progression to type 2 diabetes.

The study recruited 2,539 participants with obesity, of whom 1,032 also had prediabetes. The study had four arms, tirzepatide at 5 mg, 10 mg, or 15 mg and placebo. Follow up was planned for 3 years. The last on-treatment review was performed at 176 weeks with an additional follow up after 17 weeks off treatment. At 176 weeks, the three treatment arms produced statistically significant weight loss of between 15.4% and 22.9% depending on the dose. (Table S4) And fewer participants in the treatment group received a diagnosis of type 2 diabetes.

The study concluded that tirzepatide treatment demonstrated a "substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes".

After the 17 week off-treatment phase, overall weight loss was reported to be between 12.3% and 17.9% (Table S5). Approximately 20% of the weight lost during the treatment phase had been regained. The confidence intervals (Fig 1B) for the data points at week 193 are discrete for each tirzepatide strength from the 176 week data point, indicating that the weight gain off treatment is statistically significant.

Weight gain after stopping weight loss treatments has been demonstrated for previous treatments including orlistat, sibutramine (withdrawn in 2010 over cardiovascular safety concerns), rimonabant (withdrawn in 2008 due to concerns over psychiatric side effects) and semaglutide.

Action: Clinicians will be aware that sustained weight loss requires long term lifestyle modification, including a calorie controlled diet and increased physical activity. The results of this study are not surprising; the weight gain observed during the off-treatment phase highlights how crucial it is for lifestyle changes to be maintained.