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Open Access 16-10-2024 | Type 1 Diabetes | Commentary

Sodium-Glucose Co-transporter-2 Inhibitors in Type 1 Diabetes Mellitus: The Framework for Recommendations for Their Potential Use

Authors: Djordje S. Popovic, Dimitrios Patoulias, Theocharis Koufakis, Paschalis Karakasis, Nikolaos Papanas

Published in: Diabetes Therapy

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Abstract

The growing prevalence of overweight/obesity, the persistence of inadequate glycemic control among the majority of affected individuals, and the still unacceptably high risk of cardiovascular morbidity and mortality among population with type 1 diabetes mellitus (T1D), impose an urgent need for the introduction of non-insulin glucose-lowering agents in the therapeutic armamentarium. Given that their antihyperglycemic mechanism of action is independent of endogenous insulin secretion and that the observed cardio-renal benefits are unrelated to their glucose-lowering properties, one can speculate that the use of sodium-glucose co-transporter-2 inhibitors (SGLT2is) could provide benefits in T1D, similar to the ones observed among individuals with type 2 diabetes mellitus, chronic kidney disease (CKD), and heart failure. Available evidence from randomized controlled trials suggests that treatment with SGLT2is as adjunct to insulin in T1D results in modest reductions in glycated hemoglobin and body weight. Additionally, SGLT2is ameliorate albuminuria, and thus delay or prevent the development of CKD in T1D. However, use of SGLT2is is associated with an increased risk of diabetic ketoacidosis (DKA) in T1D. This commentary aims at providing a framework for practical recommendations regarding the potential use of SGLT2is in adults with T1D, based on the individual’s risk level for DKA development, the presence of inadequate glycemic control and related cardio-renal complications.
Literature
1.
go back to reference Gregg EW, Buckley J, Ali MK, Davies J, Flood D, Mehta R, et al. Improving health outcomes of people with diabetes: target setting for the WHO Global Diabetes Compact. Lancet. 2023;401:1302–12.CrossRefPubMedPubMedCentral Gregg EW, Buckley J, Ali MK, Davies J, Flood D, Mehta R, et al. Improving health outcomes of people with diabetes: target setting for the WHO Global Diabetes Compact. Lancet. 2023;401:1302–12.CrossRefPubMedPubMedCentral
2.
go back to reference GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;402:203–34.CrossRef GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;402:203–34.CrossRef
3.
go back to reference Rawshani A, Rawshani A, Franzén S, Eliasson B, Svensson AM, Miftaraj M, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med. 2017;376:1407–18.CrossRefPubMed Rawshani A, Rawshani A, Franzén S, Eliasson B, Svensson AM, Miftaraj M, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med. 2017;376:1407–18.CrossRefPubMed
4.
go back to reference American Diabetes Association Professional Practice Committee. 9. Pharmacologic approaches to glycemic treatment: Standards of care in diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S158–78.CrossRef American Diabetes Association Professional Practice Committee. 9. Pharmacologic approaches to glycemic treatment: Standards of care in diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S158–78.CrossRef
5.
go back to reference Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117–314. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117–314.
6.
go back to reference Authors/Task Force Members, McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2024;26:5–17.CrossRef Authors/Task Force Members, McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2024;26:5–17.CrossRef
7.
go back to reference Dandona P, Mathieu C, Phillip M, Hansen L, Tschöpe D, Thorén F, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: the DEPICT-1 52-week study. Diabetes Care. 2018;41:2552–9.CrossRefPubMed Dandona P, Mathieu C, Phillip M, Hansen L, Tschöpe D, Thorén F, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: the DEPICT-1 52-week study. Diabetes Care. 2018;41:2552–9.CrossRefPubMed
8.
go back to reference Mathieu C, Rudofsky G, Phillip M, Araki E, Lind M, Arya N, et al. Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 study): 52-week results from a randomized controlled trial. Diabetes Obes Metab. 2020;22:1516–26.CrossRefPubMedPubMedCentral Mathieu C, Rudofsky G, Phillip M, Araki E, Lind M, Arya N, et al. Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 study): 52-week results from a randomized controlled trial. Diabetes Obes Metab. 2020;22:1516–26.CrossRefPubMedPubMedCentral
9.
go back to reference Rosenstock J, Marquard J, Laffel LM, Neubacher D, Kaspers S, Cherney DZ, et al. Empagliflozin as adjunctive to insulin therapy in type 1 diabetes: the EASE trials. Diabetes Care. 2018;41:2560–9.CrossRefPubMed Rosenstock J, Marquard J, Laffel LM, Neubacher D, Kaspers S, Cherney DZ, et al. Empagliflozin as adjunctive to insulin therapy in type 1 diabetes: the EASE trials. Diabetes Care. 2018;41:2560–9.CrossRefPubMed
10.
go back to reference Buse JB, Garg SK, Rosenstock J, Bailey TS, Banks P, Bode BW, et al. Sotagliflozin in combination with optimized insulin therapy in adults with type 1 diabetes: the North American inTandem1 Study. Diabetes Care. 2018;41:1970–80.CrossRefPubMedPubMedCentral Buse JB, Garg SK, Rosenstock J, Bailey TS, Banks P, Bode BW, et al. Sotagliflozin in combination with optimized insulin therapy in adults with type 1 diabetes: the North American inTandem1 Study. Diabetes Care. 2018;41:1970–80.CrossRefPubMedPubMedCentral
11.
go back to reference Danne T, Cariou B, Banks P, Brandle M, Brath H, Franek E, et al. HbA1c and hypoglycemia reductions at 24 and 52 weeks with sotagliflozin in combination with insulin in adults with type 1 diabetes: the European inTandem2 Study. Diabetes Care. 2018;41:1981–90.CrossRefPubMed Danne T, Cariou B, Banks P, Brandle M, Brath H, Franek E, et al. HbA1c and hypoglycemia reductions at 24 and 52 weeks with sotagliflozin in combination with insulin in adults with type 1 diabetes: the European inTandem2 Study. Diabetes Care. 2018;41:1981–90.CrossRefPubMed
12.
go back to reference Garg SK, Henry RR, Banks P, Buse JB, Davies MJ, Fulcher GR, et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes. N Engl J Med. 2017;377:2337–48.CrossRefPubMed Garg SK, Henry RR, Banks P, Buse JB, Davies MJ, Fulcher GR, et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes. N Engl J Med. 2017;377:2337–48.CrossRefPubMed
13.
go back to reference Popovic DS, Karakasis P, Koufakis T, Fragakis N, Papanas N, Mitrovic M, et al. Effect of sodium-glucose cotransporter-2 inhibitors on continuous glucose monitoring metrics, as adjunctive to insulin in adults with type 1 diabetes mellitus: a meta-analysis of randomized controlled trials. Metabolism. 2024;153: 155791.CrossRefPubMed Popovic DS, Karakasis P, Koufakis T, Fragakis N, Papanas N, Mitrovic M, et al. Effect of sodium-glucose cotransporter-2 inhibitors on continuous glucose monitoring metrics, as adjunctive to insulin in adults with type 1 diabetes mellitus: a meta-analysis of randomized controlled trials. Metabolism. 2024;153: 155791.CrossRefPubMed
14.
go back to reference Groop PH, Dandona P, Phillip M, Gillard P, Edelman S, Jendle J, Xu J, et al. Effect of dapagliflozin as an adjunct to insulin over 52 weeks in individuals with type 1 diabetes: post-hoc renal analysis of the DEPICT randomised controlled trials. Lancet Diabetes Endocrinol. 2020;8:845–54.CrossRefPubMed Groop PH, Dandona P, Phillip M, Gillard P, Edelman S, Jendle J, Xu J, et al. Effect of dapagliflozin as an adjunct to insulin over 52 weeks in individuals with type 1 diabetes: post-hoc renal analysis of the DEPICT randomised controlled trials. Lancet Diabetes Endocrinol. 2020;8:845–54.CrossRefPubMed
15.
go back to reference Cherney DZI, Bjornstad P, Perkins BA, Rosenstock J, Neubacher D, Marquard J, et al. Kidney effects of empagliflozin in people with type 1 diabetes. Clin J Am Soc Nephrol. 2021;16:1715–9.CrossRefPubMedPubMedCentral Cherney DZI, Bjornstad P, Perkins BA, Rosenstock J, Neubacher D, Marquard J, et al. Kidney effects of empagliflozin in people with type 1 diabetes. Clin J Am Soc Nephrol. 2021;16:1715–9.CrossRefPubMedPubMedCentral
16.
go back to reference van Raalte DH, Bjornstad P, Persson F, Powell DR, de Cassia CR, Wang PS, et al. The impact of sotagliflozin on renal function, albuminuria, blood pressure, and hematocrit in adults with type 1 diabetes. Diabetes Care. 2019;42:1921–9.CrossRefPubMedPubMedCentral van Raalte DH, Bjornstad P, Persson F, Powell DR, de Cassia CR, Wang PS, et al. The impact of sotagliflozin on renal function, albuminuria, blood pressure, and hematocrit in adults with type 1 diabetes. Diabetes Care. 2019;42:1921–9.CrossRefPubMedPubMedCentral
17.
go back to reference Karakasis P, Popovic DS, Patoulias D, Koufakis T, Papanas N, Fragakis N, et al. The effect of sodium-glucose cotransporter inhibitors on renal function as adjunctive to insulin in adults with type 1 diabetes: an updated multilevel meta-analysis of randomized controlled trials. Diabetes Ther. 2024;15:521–32.CrossRefPubMedPubMedCentral Karakasis P, Popovic DS, Patoulias D, Koufakis T, Papanas N, Fragakis N, et al. The effect of sodium-glucose cotransporter inhibitors on renal function as adjunctive to insulin in adults with type 1 diabetes: an updated multilevel meta-analysis of randomized controlled trials. Diabetes Ther. 2024;15:521–32.CrossRefPubMedPubMedCentral
18.
go back to reference Long B, Lentz S, Koyfman A, Gottlieb M. Euglycemic diabetic ketoacidosis: etiologies, evaluation, and management. Am J Emerg Med. 2021;44:157–60.CrossRefPubMed Long B, Lentz S, Koyfman A, Gottlieb M. Euglycemic diabetic ketoacidosis: etiologies, evaluation, and management. Am J Emerg Med. 2021;44:157–60.CrossRefPubMed
20.
go back to reference Palanca A, van Nes F, Pardo F, Ampudia Blasco FJ, Mathieu C. Real-world evidence of efficacy and safety of SGLT2 inhibitors as adjunctive therapy in adults with type 1 diabetes: a European two-center experience. Diabetes Care. 2022;45:650–8.CrossRefPubMed Palanca A, van Nes F, Pardo F, Ampudia Blasco FJ, Mathieu C. Real-world evidence of efficacy and safety of SGLT2 inhibitors as adjunctive therapy in adults with type 1 diabetes: a European two-center experience. Diabetes Care. 2022;45:650–8.CrossRefPubMed
21.
go back to reference Durán-Martínez M, Azriel S, Doulatram-Gamgaram VK, Moreno-Pérez Ó, Pinés-Corrales PJ, Tejera-Pérez C, et al. Real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes in Spain: the Dapa-ON multicenter retrospective study. Diabetes Metab. 2024;50: 101501.CrossRefPubMed Durán-Martínez M, Azriel S, Doulatram-Gamgaram VK, Moreno-Pérez Ó, Pinés-Corrales PJ, Tejera-Pérez C, et al. Real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes in Spain: the Dapa-ON multicenter retrospective study. Diabetes Metab. 2024;50: 101501.CrossRefPubMed
22.
go back to reference Seufert J, Lanzinger S, Danne T, Bramlage P, Schmid SM, Kopp F, et al. Real-world data of 12-month adjunct sodium-glucose co-transporter-2 inhibitor treatment in type 1 diabetes from the German/Austrian DPV registry: improved HbA1c without diabetic ketoacidosis. Diabetes Obes Metab. 2022;24:742–6.CrossRefPubMed Seufert J, Lanzinger S, Danne T, Bramlage P, Schmid SM, Kopp F, et al. Real-world data of 12-month adjunct sodium-glucose co-transporter-2 inhibitor treatment in type 1 diabetes from the German/Austrian DPV registry: improved HbA1c without diabetic ketoacidosis. Diabetes Obes Metab. 2022;24:742–6.CrossRefPubMed
23.
go back to reference Anson M, Zhao SS, Austin P, Ibarburu GH, Malik RA, Alam U. SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study. Diabetologia. 2023;66:1869–81.CrossRefPubMedPubMedCentral Anson M, Zhao SS, Austin P, Ibarburu GH, Malik RA, Alam U. SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study. Diabetologia. 2023;66:1869–81.CrossRefPubMedPubMedCentral
24.
go back to reference 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;42:1147–54.CrossRefPubMedPubMedCentral 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;42:1147–54.CrossRefPubMedPubMedCentral
25.
go back to reference Goldenberg RM, Gilbert JD, Hramiak IM, Woo VC, Zinman B. Sodium-glucose co-transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol. Diabetes Obes Metab. 2019;21:2192–202.CrossRefPubMed Goldenberg RM, Gilbert JD, Hramiak IM, Woo VC, Zinman B. Sodium-glucose co-transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol. Diabetes Obes Metab. 2019;21:2192–202.CrossRefPubMed
Metadata
Title
Sodium-Glucose Co-transporter-2 Inhibitors in Type 1 Diabetes Mellitus: The Framework for Recommendations for Their Potential Use
Authors
Djordje S. Popovic
Dimitrios Patoulias
Theocharis Koufakis
Paschalis Karakasis
Nikolaos Papanas
Publication date
16-10-2024
Publisher
Springer Healthcare
Published in
Diabetes Therapy
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI
https://doi.org/10.1007/s13300-024-01657-9

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