MON-726 - Same Diet, Different Incretins: Real-World Weight Loss and Body Composition Changes in A Pilot Study

Background. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the dual GIP-GLP1 RA are increasingly used for obesity management in real-world settings, often combined with dietary interventions. However, comparative data on weight loss and body composition changes under standardized dietary conditions remain limited.

Aim. To evaluate and compare weight loss and body composition changes over 6 months in patients treated with liraglutide, semaglutide, or tirzepatide, following the same protocol of very low energy ketogenic nutritional therapy (VLEKT), in a real-world pilot study.

Materials and Methods. We retrospectively analyzed 61 adults with obesity treated in routine clinical practice and assigned to liraglutide (n=20), semaglutide (n=27), or tirzepatide (n=14). All patients followed the same VLEKT (approximately 800–900 kcal/day), based on a ketogenic protocol using both meal replacements and conventional protein sources. Pharmacological treatments were titrated and personalized according to individual tolerability and clinical response. Body weight and body composition were assessed at baseline (T0), 3 months (T1), and 6 months (T2). Body composition was evaluated by dual-energy X-ray absorptiometry (DEXA). Longitudinal changes were analyzed using linear mixed-effects models with fixed effects for group, time, and their interaction, and random intercepts for subjects.

Results. At baseline, groups were not fully homogeneous, with the tirzepatide group showing higher body weight, BMI, and lean mass (p < 0.05). Over time, a significant reduction in body weight was observed in all groups (p < 0.001), with mean weight loss at 6 months of −18.8±6.3 kg for liraglutide, −19.2±7.0 kg for semaglutide, and −24.4±8.7 kg for tirzepatide. Body composition analysis showed significant reductions in fat mass, fat percentage, and visceral adipose tissue over time in all groups (all p< 0.001), with a modest but significant decrease in lean mass. No significant group/time interaction was detected for weight or DEXA-derived parameters, indicating similar trajectories of change among treatments. Differences in 6-month weight loss between groups showed a trend favoring tirzepatide but did not reach statistical significance.

Conclusions. In this real-world pilot study, the combination of a standardized VLEKT with incretin-based therapies resulted in marked weight loss and significant improvements in body composition over 6 months, in the absence of major side effects, confirming the safety of the combined approach. Although tirzepatide showed a numerically greater weight reduction, differences between treatments were not statistically significant, likely due to limited sample size. Larger, adequately powered real-world studies are needed to confirm potential differential effects among incretin-based therapies when combined with ketogenic dietary interventions.

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