TOPLINE

In a 3-year analysis of the SURMOUNT-1 trial, most participants with obesity or overweight and prediabetes who reached their lowest weight on tirzepatide had regained little of it by the end of the study — 70% regained less than 5% of their baseline weight. Even with some rebound, patients retained most of their metabolic gains — suggesting a small amount of regain is not necessarily a cause for concern.

METHODOLOGY

• Patients on obesity treatment usually reach a lowest weight, or nadir, before regaining some weight back. But how much regain should actually concern clinicians has remained an open question.
• Researchers conducted a post hoc analysis of the 3-year SURMOUNT-1 trial to assess the clinical relevance of weight nadir and subsequent weight regain, and whether that weight regain was actually associated with an increased cardiometabolic risk.
• They analyzed the data of 690 tirzepatide-treated participants (mean age, 48.5 years; 64.6% women) with obesity or overweight and prediabetes at baseline. All had taken at least 75% of their prescribed tirzepatide doses and lost at least 5% of their body weight by the time they reached their weight nadir.
• Participants had started on one of three once-weekly tirzepatide doses — 5 mg, 10 mg, or 15 mg — and were tracked over 176 weeks of treatment, with an additional 17 weeks after the drug was stopped.
• Weight regain was defined as the gap between a participant's weight nadir to their week 176 weight, expressed as a percentage of their original baseline weight; participants were then grouped by how much weight they regained (< 5%, 5% to < 10%, and ≥ 10%) both across all tirzepatide doses combined and within each individual dose.

TAKEAWAY

• At week 176, participants regained a mean of 3.8 kg, 4.4 kg, and 3.7 kg from their weight nadir on the tirzepatide 5 mg, 10 mg, and 15 mg doses, respectively — equivalent to 3.6%, 4.1%, and 3.5% of their baseline body weight. When all doses were combined, 70% of participants regained < 5% of their baseline weight, 22% regained 5% to < 10%, and 8% regained ≥ 10%.
• Participants who regained the least weight (< 5%) still held onto a median 94.8% of their nadir weight loss by week 176 — compared with 69.9% for those in the 5% to < 10% weight regain group, and 44.3% for those in the ≥ 10% weight regain group.
• Over 90% of participants converted from prediabetes to normoglycemia by week 176 regardless of weight regain; even among those who regained ≥ 10% of their weight, 91% still successfully maintained normoglycemia. While ≥ 10% weight regain did weaken some of the earlier gains in blood pressure (lipid and A1c benefits held steady), patients were still far better off metabolically than when they started.
• The proportion of patients with a high-risk waist-to-height ratio (> 0.59) fell sharply by nadir but crept back up with weight regain — staying low for those who regained the least (< 5%), and rebounding more for those who regained more (5% to < 10% and ≥ 10%).

IN PRACTICE

"Continued tirzepatide treatment appears to be associated with preservation of cardiometabolic benefits, particularly for glycemia, lipids, and blood pressure, even in the presence of moderate weight regain, suggesting an active pharmacological contribution beyond weight mediation," the authors wrote.

SOURCE

The study was led by Louis J. Aronne, MD, Comprehensive Weight Control Center, Weill Cornell Medicine, New York. It was published online in Obesity Pillars.

LIMITATIONS

The 3-year analysis of the SURMOUNT-1 trial included only participants with prediabetes; therefore, these results may not extend to those without it. Waist-to-height ratio was the only cardiometabolic marker captured at all three points — baseline, individual weight nadir, and the 176-week mark. Additional limitations included the post hoc design and a limited number of participants, especially in the ≥ 10% group.

DISCLOSURES

The study was funded by Eli Lilly and Company. Five authors disclosed being employees and shareholders of the company. Several authors reported receiving grants, personal fees, institutional research funding, advisory/consulting fees, or other ties with multiple pharmaceutical companies including Eli Lilly and Company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.