Real-World Study Reveals Significant Weight Regain After Tirzepatide Discontinuation

The dual GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) receptor agonist, tirzepatide, has demonstrated remarkable efficacy for weight loss and managing type 2 diabetes. However, many patients eventually discontinue weight loss medications due to various factors like cost, side effects, or reaching their target weight. This study addresses a critical knowledge gap: the real-world weight trajectory and extent of regain after discontinuing tirzepatide in patients with overweight or obesity.

Prior to discontinuation, patients achieved a substantial mean weight loss of 18.5% from their baseline body weight. However, this progress was largely reversed upon stopping the medication. Within 6 months of discontinuing tirzepatide, patients had, on average, regained 55% of the weight they had initially lost, corresponding to a 10.2% increase from their lowest weight. By 12 months post-discontinuation, the average weight regain reached a staggering 80% of the maximum weight lost, resulting in a 14.8% increase from their lowest weight and bringing their average weight to only 3.7% below their original baseline. A significant 75% of patients regained at least 50% of their initial tirzepatide-induced weight loss by 12 months, with p<0.001 when compared to a hypothetical group continuing therapy. Only a small fraction, 15%, of patients managed to maintain more than 75% of their initial tirzepatide-induced weight loss at the 12-month mark, highlighting the challenge of sustained weight management.