Fat and lean mass changes during incretin-based therapy with structured exercise and nutritional support: A retrospective real-world pilot study

Background Incretin-based therapies are highly effective for weight reduction, but changes in lean mass during treatment remain a clinical concern. This study evaluated changes in fat mass and lean mass in individuals receiving structured exercise and nutritional support during incretin-based therapies Methods In this single-center retrospective observational chart-review study, 11 adults who underwent 9–12 months of incretin-based therapy and were offered a program providing supervised exercise and individualized nutritional support were analyzed. No control group was included. Treatments included glucagon-like peptide-1 (GLP-1) receptor agonists and glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor co-agonists. Body composition was assessed using dual-energy X-ray absorptiometry (DXA). Data were assessed for parametric assumptions, and pre- and post-intervention comparisons were performed using paired-samples t tests. Results Significant reductions were observed in body weight (mean change: -4.99 kg [95% CI: -7.65 – -2.34]; p=0.002) and fat mass (-4.37 kg [95% CI:-6.36 – -2.39]; p<0.001), corresponding to a mean total weight reduction of 4.71% and a mean fat mass reduction of 11.06% , respectively. Lean mass did not change significantly (−0.62 kg [95% CI:-2.20 – 0.95]; p = 0.397). At the aggregate cohort-level, weight reduction composition analysis indicated that 87.58% of total weight reduction was attributable to fat mass, and 12.42% to lean mass. Conclusion Incretin-based therapy delivered within a structured exercise and nutritional support program was associated with fat-dominant weight reduction without a statistically significant change in lean mass. These findings are hypothesis-generating and warrant confirmation in adequately powered prospective controlled studies.