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Medical nutrition therapy for the management of type 2 diabetes mellitus

Nature Reviews Endocrinology (2025)Cite this article

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Abstract

Type 2 diabetes mellitus (T2DM) is a major global health concern. Medical nutrition therapy has a key role in T2DM management, with dietary interventions being central to improving glycaemic control and overall metabolic health. Growing evidence suggests that certain dietary strategies can exert direct metabolic benefits independent of weight reduction. The Mediterranean diet has consistently demonstrated metabolic and cardiovascular benefits, along with improved glycaemic control, even in the absence of substantial weight reduction. Low-energy and very-low-energy diets, characterized by moderate to severe caloric restriction, respectively, have also been associated with improvements in cardiometabolic markers and glycaemic regulation. Ketogenic diets promote nutritional ketosis and have shown benefits on glycaemic control, insulin sensitivity and other metabolic outcomes, often preceding substantial weight loss. Intermittent fasting strategies, such as alternate-day fasting or the 5:2 model, and time-restricted eating, have likewise been linked to enhanced glycaemic control and favourable metabolic and cardiovascular effects, although their long-term efficacy and safety require further investigation. This Review aims to provide an evidence-based synthesis of the main nutritional strategies used in the treatment of T2DM, with a focus on their underlying mechanisms, clinical efficacy and potential for sustainable long-term implementation.

Key points

  • Personalized medical nutrition therapy is a cornerstone of type 2 diabetes mellitus (T2DM) management, with evidence supporting its role in improving glycaemic control and insulin sensitivity and in reducing diabetes mellitus-related complications in individuals both with and without obesity.

  • The Mediterranean diet exerts beneficial effects on glycaemic control, systemic inflammation and oxidative stress via several bioactive compounds such as polyphenols and omega-3 fatty acids as well as by promoting gut microbiota health and diversity.

  • Low-energy and very-low-energy diets can induce substantial weight loss and lead to T2DM remission, particularly when implemented early in the disease course.

  • Ketogenic diets, including very-low-energy ketogenic therapies, improve glycaemic outcomes and reduce insulin resistance by inducing nutritional ketosis; however, they vary in composition and require individualized use due to potential safety concerns.

  • Intermittent fasting approaches, such as 5:2 fasting and alternate-day fasting, and time-restricted eating, show promising results for weight loss, glycaemic control and medication reduction in T2DM. Their effectiveness can be enhanced when aligned with circadian rhythms.

  • Research on integrating medical nutrition therapy with pharmacological treatments such as incretin-based therapies could provide comprehensive solutions for T2DM management.

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Fig. 1: Comparison of the Mediterranean diet, low-energy diets and ketogenic diets across multiple parameters.
Fig. 2: Overview of the main intermittent fasting strategies.
Fig. 3: Schematic representation of the molecular mechanisms through which the Mediterranean diet exerts beneficial effects in the management of type 2 diabetes mellitus.
Fig. 4: Schematic representation of the molecular mechanisms through which LEDs, VLEDs and ketogenic diets exert beneficial effects in the management of T2DM.
Fig. 5: Schematic representation of the molecular mechanisms through which intermittent fasting protocols exert beneficial effects in the management of type 2 diabetes mellitus.

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Author notes

  1. These authors contributed equally: Luigi Barrea, Ludovica Verde.

Authors and Affiliations

  1. Dipartimento di Psicologia e Scienze della Salute, Università Telematica Pegaso, Naples, Italy

    Luigi Barrea

  2. Division of Endocrinology, Department of Medicine, The University of Arizona College of Medicine, Tucson, AZ, USA

    Ludovica Verde, Lawrence J. Mandarino & Giovanna Muscogiuri

  3. Department of Public Health, University of Naples Federico II, Naples, Italy

    Ludovica Verde

  4. Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), Unità di Endocrinologia, Diabetologia e Andrologia, Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Naples, Italy

    Annamaria Colao & Giovanna Muscogiuri

  5. Dipartimento di Medicina Clinica e Chirurgia, Unità di Endocrinologia, Diabetologia ed Andrologia, Università degli Studi di Napoli Federico II, Naples, Italy

    Annamaria Colao & Giovanna Muscogiuri

  6. Cattedra Unesco “Educazione Alla Salute E Allo Sviluppo Sostenibile”, Università degli Studi di Napoli Federico II, Naples, Italy

    Annamaria Colao & Giovanna Muscogiuri

  7. Center for Disparities in Diabetes, Obesity and Metabolism, University of Arizona Health Sciences, Tucson, AZ, USA

    Lawrence J. Mandarino

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Contributions

The authors contributed equally to all aspects of the article. L.V. researched data for the article. L.B. and L.V. wrote the article. L.B., A.C., L.J.M. and G.M. reviewed and/or edited the manuscript before submission.

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Correspondence to Giovanna Muscogiuri.

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Barrea, L., Verde, L., Colao, A. et al. Medical nutrition therapy for the management of type 2 diabetes mellitus. Nat Rev Endocrinol (2025). https://doi.org/10.1038/s41574-025-01161-5

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