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.
Most tirzepatide-treated participants with prediabetes maintained limited weight regain after reaching their lowest weight, but this may not be clinically significant.
Where it sits
this study against the rest of the tirzepatide corpusSummary and findings
This study evaluated weight nadirs and weight regain in adults with obesity or overweight and prediabetes during a 3-year treatment with tirzepatide. Participants who were tirzepatide-adherent and had at least a 5% weight reduction at nadir were analyzed. The mean weight regain from nadir to Week 176 was 3.8 kg, 4.4 kg, and 3.7 kg for tirzepatide doses of 5 mg, 10 mg, and 15 mg, respectively.
Abstract
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. 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. 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. 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.). 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.
Background
The study addresses the clinical relevance of weight nadirs and subsequent weight regain in adults with obesity or overweight and prediabetes. Previous research has shown that fluctuations in body weight are common during weight management, but the significance of maintaining weight nadirs remains unclear. This study is important as it explores long-term outcomes associated with tirzepatide, an obesity medication, in a specific patient population.
Methods
This was a post hoc analysis of the phase 3, double-blind, randomized, placebo-controlled SURMOUNT-1 trial. The study included participants with obesity or overweight and at least one weight-related complication, who were tirzepatide-adherent (≥75% of doses received). The analysis focused on weight regain from nadir to Week 176, categorizing participants based on their weight regain.
Results
The mean weight regain from nadir to Week 176 was 3.8 kg for the 5 mg group, 4.4 kg for the 10 mg group, and 3.7 kg for the 15 mg group. Additionally, 70% of participants experienced <5% weight regain, while 22% had 5 to <10% regain, and 8% had ≥10% regain. The median percent of weight reduction maintenance was 94.8% for those with <5% regain, 69.9% for 5-<10%, and 44.3% for ≥10% regain.
Interpretation
The findings suggest that while tirzepatide-treated participants experienced some weight regain, the majority maintained their weight reduction and showed significant improvements in glycemic control. However, the effect sizes for weight regain are relatively small, and the clinical significance of these changes may be limited. The study's post hoc nature and focus on weight nadir may confound the interpretation of long-term outcomes.
Key findings
- Mean weight regain from nadir to Week 176 was 3.8 kg for 5 mg, 4.4 kg for 10 mg, and 3.7 kg for 15 mg.
- 70% of participants had <5% weight regain, 22% had 5 to <10%, and 8% had ≥10% weight regain.
- Median percent of weight reduction maintenance was 94.8% for <5% regain, 69.9% for 5-<10%, and 44.3% for ≥10% regain.
- At Week 176, 45%, 59%, and 68% of participants in the <5%, 5% to <10%, and ≥10% regain groups, respectively, had a reduced waist-to-height ratio.
- Over 90% of tirzepatide-treated participants converted from prediabetes to normoglycemia regardless of weight regain.
Limitations
- Post hoc analysis may limit generalizability.
- Focus on weight nadir may not capture the full clinical picture.
- Short follow-up period of 3 years.
- Single-site study may introduce bias.