Evaluation of clinical relevance of weight nadirs and weight regain during 3 years of treatment with tirzepatide in participants with obesity or overweight and prediabetes.

Objective: For adults with obesity, fluctuations in body weight are expected to occur during weight management. Weight nadirs, which can become a point of focus for people living with obesity, are often hard to maintain. This study aimed to investigate the not well-defined clinical relevance of weight nadir, especially during long-term treatment with an obesity medication. Methods: This was a post hoc analysis of the phase 3, double-blind, randomized, placebo-controlled SURMOUNT-1 3-year clinical trial in participants with obesity or overweight and at least one weight-related complication. The analysis included participants who were tirzepatide-adherent (≥75% of doses received) with obesity, or overweight, and prediabetes at randomization and had ≥5% weight reduction from baseline at time of weight nadir. Weight regain analyses from weight nadir to Week 176 included mean percent change, and participants were grouped as having <5%, 5% to <10%, and ≥10% weight regain. Results: In this post hoc analysis, the mean weight regain from nadir weight to Week 176 was 3.8 kg, 4.4 kg, and 3.7 kg for those treated with tirzepatide 5 mg, 10 mg, and 15 mg, respectively. For the pooled tirzepatide doses, 70% of participants had <5% weight regain, 22% of participants had 5 to <10% weight regain, and 8% of participants had ≥10% weight regain. The median percent of weight reduction maintenance from time of weight nadir to Week 176 was 94.8%, 69.9%, and 44.3%, for <5%, 5-<10%, and ≥10%, respectively. While at baseline 94% of tirzepatide-treated participants had high waist-to-height ratio (WHtR) (>0.59), at week 176 this had reduced to 45%, 59%, and 68% in the <5%, 5% to <10%, and ≥10% weight regain groups, respectively. At Week 176, conversion from prediabetes to normoglycemia occurred in over 90% of tirzepatide-treated participants regardless of weight regain. Conclusion: These findings suggest that most tirzepatide-treated participants with baseline prediabetes in the SURMOUNT-1 3-year study had limited weight regain after reaching weight nadir and sustained improvements in glycemia (SURMOUNT-1 ClinicalTrials.gov identifier: NCT04184622.). Clinical relevance: In the current study, 92% of prediabetes participants treated with tirzepatide in the SURMOUNT-1 3-year study had a stable weight journey. Their limited weight regain from weight nadir appears not to be clinically meaningful, as improvements in cardiometabolic risk parameters were largely maintained.