Real-world effectiveness of sodium glucose transporter 2 inhibitors among youth with type 2 diabetes
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Michal Timkovski
,
Dhruva Patel
Abstract
Objectives
Clinical trials of sodium-glucose transporter 2 inhibitors (SGLT2i) in youth with type 2 diabetes (T2D) showed significant improvement in HbA1c% and fasting plasma glucose, yet there is limited real-world data on their use. This study sought to assess real-world use and effectiveness of SGLT2i medications in management of T2D in a diverse cohort of youth.
Methods
This retrospective study analyzed youth newly prescribed a SGLT2i for management of T2D at two academic pediatric diabetes centers. Change in HbA1c, BMI, and insulin use from baseline to follow-up were evaluated for those taking SGLT2i added to their background diabetes treatment. Wilcoxon signed-rank test and McNemar’s test were used to compare paired continuous and categorical variables, respectively.
Results
A total of 81 patients with youth-onset T2D (mean age 17.3 years (SD 1.93), 63 % female, 51 % non-Hispanic Black, 13 % Hispanic, 33 % with private insurance) were prescribed SGLT2i. Among the 61 (75 %) reporting adherence or partial adherence at a median follow-up of 98 days, median HbA1c decreased from 8.4 to 7.1 % (p<0.001). There was a small but significant reduction in mean BMI Z-score from baseline to follow-up (2.66 to 2.57, p=0.0004). The proportion of patients prescribed basal insulin decreased from 44 to 34 % (p=0.03), and prandial insulin from 23 to 13 % (p=0.01).
Conclusions
Real-world use of SGLT2i in youth with T2D is associated with decreased HbA1c levels and lower BMI Z-score and may also reduce use of insulin for youth with T2D.
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Research ethics: This study was conducted in compliance with the Declaration of Helsinki and was approved with a waiver of informed consent by the institutional review boards at Johns Hopkins University and the Cincinnati Children’s Hospital Medical Center.
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Informed consent: Not applicable as study was approved with a waiver of consent.
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Author contributions: R.M.W., A.S., and E.A.B. conceived of the study. M.T., D.P., and B.M. collected data. E.A.B. completed the statistical analyses and created the figures and tables. M.T., E.A.B., A.S., and R.M.W. wrote the manuscript. All authors made critical contributions to the manuscript. All authors edited, reviewed, and approved the manuscript.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: R.M.W. receives research support as the site PI of sponsored clinical trials from Novo Nordisk, Lilly Diabetes and Sanofi. The other authors have no conflict of interest to disclose.
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Research funding: No funding was received for this study.
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Data availability: Not applicable.
References
1. Tönnies, T, Brinks, R, Isom, S, Dabelea, D, Divers, J, Mayer-Davis, EJ, et al.. Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2060: the SEARCH for diabetes in youth study. Diabetes Care 2022;46:313–20. https://doi.org/10.2337/dc22-0945.Search in Google Scholar PubMed PubMed Central
2. Mayer-Davis, EJ, Dabelea, D, Lawrence, JM. Incidence trends of type 1 and type 2 diabetes among youths, 2002-2012. N Engl J Med 2017;377:301. https://doi.org/10.1056/NEJMc1706291.Search in Google Scholar PubMed PubMed Central
3. Consortium, TR, Hannon, TS, Edelstein, SL, Arslanian, SA, Caprio, S, Leschek, EW, et al.. Impact of insulin and metformin versus metformin alone on β-cell function in youth with impaired glucose tolerance or recently diagnosed type 2 diabetes. Diabetes Care 2018;41:1717–25. https://doi.org/10.2337/dc18-0787.Search in Google Scholar PubMed PubMed Central
4. D’Adamo, E, Caprio, S. Type 2 diabetes in youth: epidemiology and pathophysiology. Diabetes Care 2011;34:S161–5. https://doi.org/10.2337/dc11-s212.Search in Google Scholar PubMed PubMed Central
5. TODAY Study Group. Long-term complications in youth-onset type 2 diabetes. N Engl J Med 2021;385:416–26. https://doi.org/10.1056/nejmoa2100165.Search in Google Scholar
6. Patel, D, Shah, AS, Magella, B, Bahrainian, M, Brown, EA, Liu, TYA, et al.. High rate of complications in a real-world cohort of youth with T2D: a multicenter analysis. J Diab Complic 2025;39:109091.10.1016/j.jdiacomp.2025.109091Search in Google Scholar PubMed PubMed Central
7. Davies, MJ, Aroda, VR, Collins, BS, Gabbay, RA, Green, J, Maruthur, NM, et al.. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American diabetes association (ADA) and the European association for the study of diabetes (EASD). Diabetes Care 2022;45:2753–86. https://doi.org/10.2337/dci22-0034.Search in Google Scholar PubMed PubMed Central
8. Hitt, TA, Hannon, TS, Magge, SN. Approach to the patient: youth-onset type 2 diabetes. J Clin Endocrinol Metab 2023;109:245–55. https://doi.org/10.1210/clinem/dgad482.Search in Google Scholar PubMed
9. Shah, AS, Barrientos-Pérez, M, Chang, N, Fu, J-F, Hannon, TS, Kelsey, M, et al.. ISPAD clinical practice consensus guidelines 2024: type 2 diabetes in children and adolescents. Horm Res Paediatr 2024;97:555–83. https://doi.org/10.1159/000543033.Search in Google Scholar PubMed PubMed Central
10. Laffel, LM, Danne, T, Klingensmith, GJ, Tamborlane, WV, Willi, S, Zeitler, P, et al.. Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): a multicentre, randomised, double-blind, parallel group, phase 3 trial. Lancet Diabetes Endocrinol 2023;11:169–81.10.1007/s13300-024-01555-0Search in Google Scholar PubMed PubMed Central
11. FDA Approves New Class of Medicines to Treat Pediatric Type 2 Diabetes [press release]. 2023.Search in Google Scholar
12. Parkinson, J, Tang, W, Johansson, C-C, Boulton, DW, Hamrén, B. Comparison of the exposure–response relationship of dapagliflozin in adult and paediatric patients with type 2 diabetes mellitus. Diabetes Obes Metabol 2016;18:685–92. https://doi.org/10.1111/dom.12647.Search in Google Scholar PubMed
13. Abdul-Ghani, MA, Norton, L, DeFronzo, RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev 2011;32:515–31. https://doi.org/10.1210/er.2010-0029.Search in Google Scholar PubMed
14. Davidson, JA, Kuritzky, L. Sodium glucose co-transporter 2 inhibitors and their mechanism for improving glycemia in patients with type 2 diabetes. Postgrad Med J 2014;126:33–48. https://doi.org/10.3810/pgm.2014.10.2819.Search in Google Scholar PubMed
15. Fakhrolmobasheri, M, Abhari, AP, Manshaee, B, Heidarpour, M, Shafie, D, Mohammadbeigi, E, et al.. Effect of sodium–glucose cotransporter 2 inhibitors on insulin resistance; a systematic review and meta-analysis. Acta Diabetol 2023;60:191–202. https://doi.org/10.1007/s00592-022-01981-1.Search in Google Scholar PubMed
16. Wilding, JP, Woo, V, Soler, NG, Pahor, A, Sugg, J, Rohwedder, K, et al.. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin. Ann Intern Med 2012;156:405–15. https://doi.org/10.7326/0003-4819-156-6-201203200-00003.Search in Google Scholar PubMed
17. Ferrannini, E, Ramos, SJ, Salsali, A, Tang, W, List, JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 2010;33:2217–24. https://doi.org/10.2337/dc10-0612.Search in Google Scholar PubMed PubMed Central
18. Seidu, S, Alabraba, V, Davies, S, Newland-Jones, P, Fernando, K, Bain, SC, et al.. SGLT2 inhibitors – the new standard of care for cardiovascular, renal and metabolic protection in type 2 diabetes: a narrative review. Diabetes Ther 2024;15:1099–124. https://doi.org/10.1007/s13300-024-01550-5.Search in Google Scholar PubMed PubMed Central
19. Tamborlane, WV, Laffel, LM, Shehadeh, N, Isganaitis, E, Van Name, M, Ratnayake, J, et al.. Efficacy and safety of dapagliflozin in children and young adults with type 2 diabetes: a prospective, multicentre, randomised, parallel group, phase 3 study. Lancet Diabetes Endocrinol 2022;10:341–50.10.1016/S2213-8587(22)00052-3Search in Google Scholar PubMed PubMed Central
20. ElSayed, NA, Aleppo, G, Bannuru, RR, Bruemmer, D, Collins, BS, Ekhlaspour, L, et al., American Diabetes Association Professional Practice C. 14. Children and adolescents: standards of care in diabetes-2024. Diabetes Care 2024;47:S258-1. https://doi.org/10.2337/dc24-s014.Search in Google Scholar
21. Tanaka, A, Shimabukuro, M, Teragawa, H, Okada, Y, Takamura, T, Taguchi, I, et al.. Comparison of the clinical effect of empagliflozin on glycemic and non-glycemic parameters in Japanese patients with type 2 diabetes and cardiovascular disease treated with or without baseline metformin. Cardiovasc Diabetol 2021;20:160. https://doi.org/10.1186/s12933-021-01352-0.Search in Google Scholar PubMed PubMed Central
22. Magge, SN, Wolf, RM, Pyle, L, Brown, EA, Benavides, VC, Bianco, ME, et al.. The coronavirus disease 2019 pandemic is associated with a substantial rise in frequency and severity of presentation of youth-onset type 2 diabetes. J Pediatr 2022;251:51–9 e2. https://doi.org/10.1016/j.jpeds.2022.08.010.Search in Google Scholar PubMed PubMed Central
23. Tsapas, A, Karagiannis, T, Kakotrichi, P, Avgerinos, I, Mantsiou, C, Tousinas, G, et al.. Comparative efficacy of glucose-lowering medications on body weight and blood pressure in patients with type 2 diabetes: a systematic review and network meta-analysis. Diabetes Obes Metab 2021;23:2116–24. https://doi.org/10.1111/dom.14451.Search in Google Scholar PubMed
24. Wilding, JP, Woo, V, Soler, NG, Pahor, A, Sugg, J, Rohwedder, K, et al.. Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann Intern Med 2012;156:405–15. https://doi.org/10.7326/0003-4819-156-6-201203200-00003.Search in Google Scholar PubMed
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/jpem-2025-0243).
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