Optimizing nutritional strategies in type 2 diabetes patients receiving sodium-glucose cotransporter-2 inhibitor therapy
DOI:
https://doi.org/10.18203/issn.2454-2156.IntJSciRep20253330Keywords:
Sodium-glucose cotransporter-2 inhibitors, Carbohydrate metabolism, Glycosuria, Sarcopenia, Medical nutritional therapyAbstract
Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve glycaemic control via insulin-independent glycosuria and offer cardiovascular and renal benefits. However, their safety and effectiveness are significantly influenced by dietary context, particularly in high-carbohydrate environments like India, where refined grain consumption and periodic fasting are common. This review discusses how SGLT2 inhibitor-induced energy loss, ketone production, and fluid shifts interact with regional dietary patterns. Key nutritional concerns arise in this context, including sarcopenia from caloric and protein deficits, euglycemic diabetic ketoacidosis (euDKA) triggered by carbohydrate restriction, and volume depletion due to inadequate hydration. To manage these risks, targeted nutritional strategies are essential. These include moderating carbohydrate intake (around 45-50% of total energy), maintaining sufficient protein intake (15-20% of energy), maintaining hydration (2.0-2.5 L/day), and avoiding ketogenic or overly carbohydrate restrictive diets. Furthermore, individualized dietary planning during religious fasts is important for maintaining metabolic balance. In South Asian populations, where dietary habits are deeply rooted in culture, nutrition counseling is not merely supportive but holds a central role in optimizing therapeutic outcomes with SGLT2 inhibitors.
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References
International Diabetes Federation. IDF Diabetes Atlas. 10th ed. Brussels: International Diabetes Federation; 2021. Available at: https://diabetesatlas.org/. Accessed on 4 July 2025.
Chauhan S, Khatib MN, Ballal S, Bansal P, Bhopte K, Gaidhane AM, et al The rising burden of diabetes and state-wise variations in India: insights from the Global Burden of Disease Study 1990-2021 and projections to 2031. Front Endocrinol (Lausanne). 2025;16:1505143. DOI: https://doi.org/10.3389/fendo.2025.1505143
Krishnan D, Manasa VS, Gayathri R, Shobana S, Mohan V. Role of macronutrients and suitability of upcoming dietary trends for Asian adults with type 2 diabetes. J Diabetol. 2021;12(4):408-15. DOI: https://doi.org/10.4103/jod.jod_50_21
Salis S, Virmani A, Priyambada L, Mohan M, Hansda K, Beaufort C. "Old is Gold": How traditional Indian dietary practices can support pediatric diabetes management. Nutrients. 2021;13(12):4427. DOI: https://doi.org/10.3390/nu13124427
Wolever TM, Mehling C. Long-term effect of varying the source or amount of dietary carbohydrate on postprandial plasma glucose, insulin, triacylglycerol, and free fatty acid concentrations in subjects with impaired glucose tolerance. Am J Clin Nutr. 2003;77(3):612-21. DOI: https://doi.org/10.1093/ajcn/77.3.612
Gronda EG, Vanoli E, Iacoviello M, Urbinati S, Caldarola P, Colivicchi F, et al Renal effects of SGLT2 inhibitors in cardiovascular patients with and without chronic kidney disease: focus on heart failure and renal outcomes. Eur Heart J Suppl. 2020;22(E):E172-81.
Kurczyński D, Hudzik B, Jagosz M, Zabierowski J, Nowak J, Tomasik A, et al Sodium-glucose cotransporter-2 inhibitors-from the treatment of diabetes to therapy of chronic heart failure. J Cardiovasc Dev Dis. 2022;9(7):225. DOI: https://doi.org/10.3390/jcdd9070225
Bonora BM, Avogaro A, Fadini GP. Extraglycemic effects of SGLT2 inhibitors: A review of the evidence. Diabetes Metab Syndr Obes. 2020;13:161-74. DOI: https://doi.org/10.2147/DMSO.S233538
Danne T, Garg S, Peters AL, Buse JB, Mathieu C, Pettus JH, et al. International consensus on risk management of diabetic ketoacidosis in patients with type 1 diabetes treated with sodium-glucose cotransporter (SGLT) inhibitors. Diabetes Care. 2019;42(6):1147-54. DOI: https://doi.org/10.2337/dc18-2316
Taylor SI, Blau JE, Rother KI. SGLT2 inhibitors may predispose to ketoacidosis. J Clin Endocrinol Metab. 2015;100(8):2849-52. DOI: https://doi.org/10.1210/jc.2015-1884
Calado J, Santer R, Müller D, Koepsell H, Köricke R, Tonelli E, et al. Familial renal glucosuria: SLC5A2 mutation analysis reveals a salt-wasting condition. Kidney Int. 2006;69(5):852-5. DOI: https://doi.org/10.1038/sj.ki.5000194
Wright EM. Renal Na(+)-glucose cotransporters. Am J Physiol Renal Physiol. 2001;280(1):F10-8. DOI: https://doi.org/10.1152/ajprenal.2001.280.1.F10
Çetin D, Bilgili E, Komaç Ö, Yetişken M, Güney E. Effects of empagliflozin on sarcopenia risk, body composition, and muscle strength in type 2 diabetes: a 24 week real world observational study. Medicina. 2025;61(7):1152. DOI: https://doi.org/10.3390/medicina61071152
Saisho Y. SGLT2 Inhibitors: the Star in the Treatment of Type 2 Diabetes? Diseases. 2020;8(2):14. DOI: https://doi.org/10.3390/diseases8020014
Yabe D, Iwasaki M, Kuwata H, Haraguchi T, Hamamoto Y, Kurose T, et al. Sodium-glucose co-transporter-2 inhibitor use and dietary carbohydrate intake in Japanese individuals with type 2 diabetes: a randomized, open-label, 3-arm parallel comparative, exploratory study. Diabetes Obes Metab. 2017;19(5):739-43. DOI: https://doi.org/10.1111/dom.12848
Boeder SC, Gregory JM, Giovannetti ER, Pettus JH. SGLT2 Inhibition Increases Fasting Glucagon but Does Not Restore the Counterregulatory Hormone Response to Hypoglycemia in Participants With Type 1 Diabetes. Diabetes. 2022;71(3):11-519. DOI: https://doi.org/10.2337/db21-0769
Ferrannini G, Hach T, Crowe S, Sanghvi A, Hall KD, Ferrannini E. Energy balance after sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015;38(9):1730-5. DOI: https://doi.org/10.2337/dc15-0355
Hayami T, Kato Y, Kamiya H, Kondo M, Naito E, Sugiura Y, et al. Case of ketoacidosis by a sodium-glucose cotransporter 2 inhibitor in a diabetic patient with a low-carbohydrate diet. J Diabetes Investig. 2015;6(5):587-90. DOI: https://doi.org/10.1111/jdi.12330
Franz MJ, Evert AB, Boucher JL. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care. 2015;38(1):1-11.
Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care. 2015;38(9):1638-42. DOI: https://doi.org/10.2337/dc15-1380
Thomas MC, Cherney DZ. The actions of SGLT2 inhibitors on metabolism, renal function, and blood pressure. Diabetologia. 2018;61(10):2098-107. DOI: https://doi.org/10.1007/s00125-018-4669-0
Cianciolo G, De Pascalis A, Capelli I, Gasperoni L, Di Lullo L, Bellasi A, et al. Mineral and electrolyte disorders with SGLT2i therapy. JBMR Plus. 2019;3(11):e10242. DOI: https://doi.org/10.1002/jbm4.10242
Nilsson CN, Ersbøll MK, Gustafsson F. Haemodynamic effects of sodium-glucose cotransporter 2 inhibitor treatment in chronic heart failure patients. Card Fail Rev. 2024;10:e09. DOI: https://doi.org/10.15420/cfr.2023.25
Inoue K, Sato M, Yoshida M, Sakaue H, Tamaki M. Effects of SGLT2 inhibitor treatment on FGF21 secretion and compensatory hyperphagia in type 2 diabetes patients. Endocr J. 2019;66(8):681-7.
Rajeev SP, Cuthbertson DJ, Wilding JP. Energy balance and metabolic changes with sodium-glucose co-transporter 2 inhibition. Diabetes Obes Metab. 2016;18:125-34. DOI: https://doi.org/10.1111/dom.12578
Yabe D, Seino Y. SGLT2 inhibitors and dietary carbohydrates: Clinical implications. Diabetes Obes Metab. 2015;17(5):477-82.
Goldenberg RM, Berard LD. Integrating SGLT2 inhibitors in clinical practice: Nutrition and lifestyle implications. Can J Diabetes. 2022;46(2):101-8.
Indian Council of Medical Research–National Institute of Nutrition. Dietary Guidelines for Indians-2024. Hyderabad: NIN, ICMR. Report No.: DGI07052024P. 2024.
Anitha S, Kane-Potaka J, Tsusaka TW, Botha R, Rajendran A, Givens DI, et al. A systematic review and meta-analysis of the potential of millets for managing and reducing the risk of developing diabetes mellitus. Front Nutr. 2021;8:687428. DOI: https://doi.org/10.3389/fnut.2021.687428
National Institute of Nutrition, Indian Council of Medical Research. What India Eats. Hyderabad: ICMR-NIN. 2020;31-80.
Hassanein M, Bashier A, Randeree H, Abouelmagd M, AlBaker W, Afandi B, et al. Use of SGLT2 inhibitors during Ramadan: An expert panel statement. Diabetes Res Clin Pract. 2020;169:108465. DOI: https://doi.org/10.1016/j.diabres.2020.108465
Evert AB, Dennison M, Gardner CD, Garvey WT, Lau KHK, MacLeod J, et al. Nutrition therapy for adults with diabetes or prediabetes: A consensus report. Diabetes Care. 2019;42(5):731-54. DOI: https://doi.org/10.2337/dci19-0014
Chawla R, Madhu SV, Makkar BM, Ghosh S, Saboo B, Kalra S. RSSDI-ESI Clinical Practice Recommendations for the Management of Type 2 Diabetes Mellitus 2023. Int J Diabetes Dev Ctries. 2023;43(1):S1-292. DOI: https://doi.org/10.4103/ijem.IJEM_225_20
Franz MJ, Evert AB, Boucher JL. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care. 2015;38(1):1-11.
Merrill JD, Soliman D, Kumar N, Lim S, Shariff AI, Yancy WS. Low-carbohydrate and very-low-carbohydrate diets in patients with diabetes. Diabetes Spectr. 2020;33(2):133-42. DOI: https://doi.org/10.2337/ds19-0070
Committee on the Proper Use of SGLT2 Inhibitors. Recommendations on the proper use of SGLT2 inhibitors. J Diabetes Investig. 2020;11(1):257-61. DOI: https://doi.org/10.1111/jdi.13160
Yalçın N, Aktaş S, Uyar S, Koca N. Impact of SGLT2 inhibitors on cardiovascular risk scores, metabolic parameters, and laboratory profiles in type 2 diabetes. Life (Basel). 2025;15(5):722. DOI: https://doi.org/10.3390/life15050722
Beshyah SA, Hafidh K, Shaikh TG. Evolving physicians’ perceptions and practices regarding use of SGLT2 inhibitors for type 2 diabetes during Ramadan fasting. Diabetes Res Clin Pract. 2020;168:108389. DOI: https://doi.org/10.1016/j.diabres.2020.108389
Igarashi H, Uchino H, Kanaguchi M, Hisanaga K, Sato G, Yoshikawa F, et al. SGLT2 inhibitor versus carbohydrate-restricted isocaloric diet: reprogramming substrate oxidation in type 2 diabetes. Diabetol Metab Syndr. 2023;15(1):25. DOI: https://doi.org/10.1186/s13098-023-00990-6