Pharmacological Management of Diabesity: Current and Emerging Therapies.

Martina Galasso, Mariangela Caporusso, Alessandra Volatile, Ludovica Verde, Katherine Esposito, Francesco Giorgino, Sebastio Perrini, Annamaria Colao, Luigi Barrea, Giovanna Muscogiuri

Journal: Current obesity reports 2026;15(1):5

PMID: 41528611

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Abstract

PURPOSE OF REVIEW

This review aims to provide a comprehensive synthesis of current clinical evidence on the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonists on body mass index (BMI), body composition, and glucose metabolism in patients with obesity and type 2 diabetes mellitus (T2DM), a condition often referred to as "diabesity."

RECENT FINDINGS

The coexistence of obesity and T2DM represents a major clinical and public health challenge due to their synergistic effects on metabolic dysfunction and the increased risk of cardiovascular and renal complications. Traditional approaches focused solely on glycemic control have proven insufficient to address the intertwined pathophysiology of excess adiposity and impaired glucose metabolism. Recently, novel pharmacological agents, including SGLT2 inhibitors, GLP-1 RAs, and dual GIP/GLP-1 receptor agonists, have demonstrated dual benefits in improving glycemic control and reducing body weight. These drugs act through distinct but complementary mechanisms-such as promoting glycosuria, enhancing satiety, delaying gastric emptying, and modulating energy homeostasis-resulting in significant reductions in BMI and visceral fat. Among these agents, tirzepatide has shown superior efficacy in improving metabolic parameters and body composition compared with single receptor agonists. Understanding the multifaceted metabolic benefits of these pharmacotherapies is essential for optimizing individualized therapeutic strategies for patients with diabesity. Integrating these agents into comprehensive diabetes care allows clinicians to more effectively target the complex pathophysiology of diabesity, ultimately improving long-term metabolic and clinical outcomes in this growing patient population.

Address: Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, Naples, 80131, Italy.; Endocrinology Unit, Regional General Hospital "Francesco Miulli", Acquaviva delle Fonti, Bari, 70021, IT, Italy.; Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.; Department of Public Health, University of Naples Federico II, Via Sergio Pansini 5, Naples, 80131, Italy.; Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.; Unit of Endocrinology and Metabolic Diseases, AOU University of Campania "Luigi Vanvitelli", Naples, Italy.; Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, 70124, IT, Italy.; Endocrinology Unit, Regional General Hospital "Francesco Miulli", Acquaviva delle Fonti, Bari, 70021, IT, Italy.; Section of Endocrinology, Department of Medicine and Surgery, Libera Università Mediterranea (LUM), Casamassima, Bari, IT, 70010, Italy.; Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, Naples, 80131, Italy.; Dipartimento Di Medicina Clinica E Chirurgia, Unità Di Endocrinologia, Università Degli Studi Di Napoli Federico II, Naples, 80131, Italy.; Cattedra Unesco "Educazione Alla Salute E Allo Sviluppo Sostenibile", University Federico II, Naples, 80131, Italy.; Dipartimento Di Psicologia e Scienze Della Salute, Università Telematica Pegaso, Centro Direzionale, Via Porzio, Isola F2, Naples, 80143, Italy.; Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, Naples, 80131, Italy. [email protected].; Dipartimento Di Medicina Clinica E Chirurgia, Unità Di Endocrinologia, Università Degli Studi Di Napoli Federico II, Naples, 80131, Italy. [email protected].; Cattedra Unesco "Educazione Alla Salute E Allo Sviluppo Sostenibile", University Federico II, Naples, 80131, Italy. [email protected].; University of Naples Federico II, Via Sergio Pansini 5, Naples, 80031, Italy. [email protected].

DOI: 10.1007/s13679-025-00681-5

MeSH Terms: Humans, Diabetes Mellitus, Type 2, Sodium-Glucose Transporter 2 Inhibitors, Obesity, Hypoglycemic Agents, Glucagon-Like Peptide-1 Receptor Agonists, Gastric Inhibitory Polypeptide, Body Mass Index, Body Composition, Blood Glucose, Diabesity