Tirzepatide's impact on metabolic adaptation and long-term weight regain to be investigated

Obesity is a global health crisis, often leading to severe comorbidities like cardiovascular disease. While lifestyle modifications are foundational, their long-term efficacy is frequently hampered by weight regain. This phenomenon is largely attributed to metabolic adaptation, characterized by reduced total energy expenditure (due to lean and fat mass loss) and increased appetite. Anti-obesity medications (AOMs) like tirzepatide are increasingly vital as adjuvants to lifestyle changes. This study aims to fill a critical gap by exploring how tirzepatide influences metabolic adaptation and its association with subsequent weight regain.

This abstract outlines the protocol for a prospective follow-up study to a previous 18-week lifestyle intervention (NCT04081337). In the initial phase, 55 participants with obesity aimed for 10% body weight loss, receiving either tirzepatide (15mg after titration) or placebo. Before and after this intervention, energy expenditure was measured via 48-h room indirect calorimetry, and body weight and composition via dual-X-ray absorptiometry to assess metabolic adaptation. The current follow-up will invite these participants back at 12, 18, and 24 months post-intervention to measure body weight and composition, exploring the association between initial metabolic adaptation and long-term changes.

This abstract describes a study protocol and therefore presents no direct findings or numerical results from the investigation itself. It details the design to assess long-term outcomes of a previous 18-week lifestyle intervention for obesity (NCT04081337) where 55 participants received either tirzepatide (15mg after titration) or placebo. The prior intervention aimed for 10% body weight loss. The follow-up will measure body weight and composition at 12, 18, and 24 months post-intervention. The primary objective is to explore the association between initial metabolic adaptation (measured via 48-h room indirect calorimetry and dual-X-ray absorptiometry) and subsequent weight regain. Secondary objectives include comparing weight and fat mass changes between the tirzepatide and placebo groups, and investigating whether metabolic adaptation mediates these effects. This design aims to elucidate the mechanisms underlying tirzepatide's efficacy in preventing weight regain.