Nutrition and Physical Activity in Optimizing Weight Loss and Lean Mass Preservation in the Incretin-Based Medications Era - Narrative Review

Sep 30, 2026

Incretin-based medications have significantly changed obesity management by enabling substantial body-weight reduction, yet they can also drive rapid and pronounced loss of mass. This narrative review synthesizes evidence on how nutritional and physical-activity strategies can preserve lean mass, improve functional outcomes, and reduce risk of long-term complications. A literature search up to 31 October 2025 evaluates nutritional approaches, adjunctive supplementation, and structured training combining aerobic and resistance exercise, alongside emerging pharmacologic and microbiota-modulating options.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages28

Reading Time1 h 11 min

AccessFree to download

Abstract

Background/Objectives

Methods

Results

Conclusions

Introduction

Obesity as a health risk

Etiology and clinical vs preclinical obesity

Emergence of GLP-1 receptor agonists

Review Nutrition and Physical Activity in Optimizing Weight Loss and Lean Mass Preservation in the Incretin-Based Medications Era: A Narrative Review Luisa Barana 1,†, Michelantonio De Fano 2,†, Massimiliano Cavallo 3,*, Marcello Manco 2, Deborah Prete 4,*, Carmine Giuseppe Fanelli 4,5, Francesca Porcellati 5,‡ and Roberto Pippi 4,‡ Academic Editor: Chengwen Sun Received: 5 November 2025 Revised: 24 December 2025 Accepted: 30 December 2025 Published: 31 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Diabetology and Endocrinology, Degli Infermi New Hospital of Biella, 13875 Ponderano, Italy; [luisa.barana@gmail.com](luisa.barana@gmail.com) 2 Endocrine and Metabolic Sciences Section, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy; [michelantonio.defano@gmail.com](michelantonio.defano@gmail.com) (M.D.F.); [marcellomanco.mm@gmail.com](marcellomanco.mm@gmail.com) (M.M.) 3 Internal Medicine and Vascular Diseases Unit, Azienda Ospedaliera Santa Maria, 05100 Terni, Italy 4 Healthy Lifestyle Institute, Centro Universitario Ricerca Interdipartimentale Attività Motoria (C.U.R.I.A.Mo.), Department of Medicine and Surgery, University of Perugia, Via G. Bambagioni, 19, 06126 Perugia, Italy; [carmine.fanelli@unipg.it](carmine.fanelli@unipg.it) (C.G.F.); [roberto.pippi@unipg.it](roberto.pippi@unipg.it) (R.P.) 5 Department of Medicine and Surgery, Perugia University Medical School, 06126 Perugia, Italy; [f.porcellati.fp@gmail.com](f.porcellati.fp@gmail.com) * [Correspondence: massimilianocavallotr@gmail.com](Correspondence: massimilianocavallotr@gmail.com) (M.C.); [deborah.prete@collaboratori.unipg.it](deborah.prete@collaboratori.unipg.it) (D.P.)† These authors contributed equally to this work. ‡ These authors contributed equally to this work. Abstract Background/Objectives: Incretin-based medications have transformed obesity management by enabling substantial body weight reduction. However, the rapid and pronounced loss of body mass necessitates a comprehensive, multidisciplinary approach incorporating nutritional and physical activity strategies to preserve lean mass, optimize functional outcomes, and prevent long-term complications. This narrative review provides a critical overview of this emerging clinical concern, which is expected to gain increasing relevance in the coming years. Methods: A literature review was conducted up to 31 October 2025, focusing on studies addressing nutritional, physical activity, and adjunctive interventionsin adults with obesity treated with incretin-based medications. Results: Incretin-based agents induce significant weight loss, comparable to bariatric surgery, predominantly targeting adipose tissue. Nevertheless, these medications also cause rapid reductions in muscle and bone mass, often accompanied by nutrient deficiencies, which may compromise metabolic health and physical function. Tailored nutritional strategies—including hypocaloric diets enriched in protein and fiber, as well as amino acid, vitamin, and mineral supplementation—are critical to preserve lean mass and support sustained weight maintenance. Concurrently, structured, supervised physical activity, encompassing aerobics, resistance, and strength training, mitigates muscle loss and enhances functional capacity. Emerging pharmacological agents designed to promote adipose tissue reduction while preserving lean mass, as well as interventions targeting gut microbiota modulation, may represent promising adjunctive strategies to optimize long-term outcomes further. Conclusions: While incretin-based medications produce substantial weight loss, their impact on lean mass underscores the necessity of integrating personalized nutrition, supplementation, and structured exercise to preserve muscle, prevent malnutrition

FAQs

Why do incretin-based medications require a nutrition and physical-activity strategy?

They can cause rapid weight loss but also reduce muscle and bone mass, frequently with nutrient deficiencies. A combined approach helps preserve lean mass, support function, and prevent long-term complications.

What nutritional interventions does the review highlight for lean mass preservation?

It emphasizes hypocaloric diets enriched with protein and fiber, plus supplementation with amino acids, vitamins, and minerals to maintain muscle and support sustained weight control.

How does exercise help when treating obesity with incretin-based medications?

Structured, supervised physical activity—combining aerobic and resistance/strength training—can mitigate muscle loss and improve functional capacity while supporting ongoing weight maintenance.

Sep 30, 2026

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