International Consensus on Risk Management of Diabetic Ketoacidosis in Patients With Type 1 Diabetes Treated With Sodium-Glucose Cotransporter (SGLT) Inhibitors

Overview

Journal Diabetes Care

Specialty Endocrinology

Date 2019 Feb 8

PMID 30728224

Citations 119

Authors

Thomas Danne

Satish Garg

Anne L Peters

John B Buse

Chantal Mathieu

Jeremy H Pettus

Charles M Alexander

Tadej Battelino

F Javier Ampudia-Blasco

Bruce W Bode

Bertrand Cariou

Kelly L Close

Paresh Dandona

Sanjoy Dutta

Ele Ferrannini

Spiros Fourlanos

George Grunberger

Simon R Heller

Robert R Henry

Martin J Kurian

Jake A Kushner

Tal Oron

Christopher G Parkin

Thomas R Pieber

Helena W Rodbard

Desmond Schatz

Jay S Skyler

William V Tamborlane

Koutaro Yokote

Moshe Phillip

Affiliations

Soon will be listed here.

Abstract

Sodium-glucose cotransporter (SGLT) inhibitors are new oral antidiabetes medications shown to effectively reduce glycated hemoglobin (A1C) and glycemic variability, blood pressure, and body weight without intrinsic properties to cause hypoglycemia in people with type 1 diabetes. However, recent studies, particularly in individuals with type 1 diabetes, have demonstrated increases in the absolute risk of diabetic ketoacidosis (DKA). Some cases presented with near-normal blood glucose levels or mild hyperglycemia, complicating the recognition/diagnosis of DKA and potentially delaying treatment. Several SGLT inhibitors are currently under review by the U.S. Food and Drug Administration and European regulatory agencies as adjuncts to insulin therapy in people with type 1 diabetes. Strategies must be developed and disseminated to the medical community to mitigate the associated DKA risk. This Consensus Report reviews current data regarding SGLT inhibitor use and provides recommendations to enhance the safety of SGLT inhibitors in people with type 1 diabetes.

Citing Articles

The effects of empagliflozin in patients with type 1 diabetes: Results of a 12-week, double-blind, randomized, placebo-controlled clinical trial.

Najafipour M, Najafipour F, Ostadrahimi A, Ghavami M, Razaghi Z, Tutunchi H Health Promot Perspect. 2025; 14(4):380-387.

PMID: 40041732 PMC: 11873775. DOI: 10.34172/hpp.42486.

Breath Acetone Correlates with Capillary β-hydroxybutyrate in Type 1 Diabetes.

Jones K, Petersen M, Markov A, Salam M, Krutilova P, McKee A medRxiv. 2025; .

PMID: 39974120 PMC: 11838673. DOI: 10.1101/2025.01.30.25321320.

Risk of diabetic ketoacidosis caused by sodium glucose cotransporter-2 inhibitors in patients with type 1 diabetes: a systematic review and network meta-analysis of randomized controlled trials.

Liu Y, Yang S, Jiang A, Zou D, Chen Z, Su N Front Endocrinol (Lausanne). 2025; 15:1453067.

PMID: 39957850 PMC: 11826237. DOI: 10.3389/fendo.2024.1453067.

Understanding the disease: euglycemic ketoacidosis with SGLT2 inhibitors.

Malherbe J, Du Cheyron D, Valette X Intensive Care Med. 2025; .

PMID: 39899035 DOI: 10.1007/s00134-025-07806-3.

Subcutaneous weekly semaglutide with automated insulin delivery in type 1 diabetes: a double-blind, randomized, crossover trial.

Pasqua M, Tsoukas M, Kobayati A, Aboznadah W, Jafar A, Haidar A Nat Med. 2025; .

PMID: 39794615 DOI: 10.1038/s41591-024-03463-z.

References

Polonsky W, Anderson B, Lohrer P, Welch G, Jacobson A, Aponte J . Assessment of diabetes-related distress. Diabetes Care. 1995; 18(6):754-60. DOI: 10.2337/diacare.18.6.754. View

Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T . Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014; 124(2):499-508. PMC: 3904627. DOI: 10.1172/JCI72227. View

Peters A, Buschur E, Buse J, Cohan P, Diner J, Hirsch I . Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015; 38(9):1687-93. PMC: 4542270. DOI: 10.2337/dc15-0843. View

Zinman B, Wanner C, Lachin J, Fitchett D, Bluhmki E, Hantel S . Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015; 373(22):2117-28. DOI: 10.1056/NEJMoa1504720. View

Peyrot M, Skovlund S, Landgraf R . Epidemiology and correlates of weight worry in the multinational Diabetes Attitudes, Wishes and Needs study. Curr Med Res Opin. 2009; 25(8):1985-93. DOI: 10.1185/03007990903073654. View

Ogawa W, Sakaguchi K . Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig. 2016; 7(2):135-8. PMC: 4773669. DOI: 10.1111/jdi.12401. View

Sands A, Zambrowicz B, Rosenstock J, Lapuerta P, Bode B, Garg S . Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes. Diabetes Care. 2015; 38(7):1181-8. PMC: 4831906. DOI: 10.2337/dc14-2806. View

Henry R, Thakkar P, Tong C, Polidori D, Alba M . Efficacy and Safety of Canagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, as Add-on to Insulin in Patients With Type 1 Diabetes. Diabetes Care. 2015; 38(12):2258-65. DOI: 10.2337/dc15-1730. View

Candelario N, Wykretowicz J . The DKA that wasn't: a case of euglycemic diabetic ketoacidosis due to empagliflozin. Oxf Med Case Reports. 2016; 2016(7):144-6. PMC: 4962888. DOI: 10.1093/omcr/omw061. View

10.

Foster D, McGarry J . The regulation of ketogenesis. Ciba Found Symp. 1982; 87:120-31. DOI: 10.1002/9780470720691.ch7. View

11.

Taylor S, Blau J, Rother K . SGLT2 Inhibitors May Predispose to Ketoacidosis. J Clin Endocrinol Metab. 2015; 100(8):2849-52. PMC: 4525004. DOI: 10.1210/jc.2015-1884. View

12.

Klocker A, Phelan H, Twigg S, Craig M . Blood β-hydroxybutyrate vs. urine acetoacetate testing for the prevention and management of ketoacidosis in Type 1 diabetes: a systematic review. Diabet Med. 2013; 30(7):818-24. DOI: 10.1111/dme.12136. View

13.

Kibbey R . SGLT-2 inhibition and glucagon: Cause for alarm?. Trends Endocrinol Metab. 2015; 26(7):337-8. PMC: 4490128. DOI: 10.1016/j.tem.2015.05.011. View

14.

McCrimmon R, Henry R . SGLT inhibitor adjunct therapy in type 1 diabetes. Diabetologia. 2018; 61(10):2126-2133. PMC: 6133151. DOI: 10.1007/s00125-018-4671-6. View

15.

Albanese-ONeill A, Wu M, Miller K, Jacobsen L, Haller M, Schatz D . Poor Adherence to Ketone Testing in Patients With Type 1 Diabetes. Diabetes Care. 2017; 40(4):e38-e39. DOI: 10.2337/dc16-2620. View

16.

Lyons S, Hermann J, Miller K, Hofer S, Foster N, Rami-Merhar B . Use of Adjuvant Pharmacotherapy in Type 1 Diabetes: International Comparison of 49,996 Individuals in the Prospective Diabetes Follow-up and T1D Exchange Registries. Diabetes Care. 2017; 40(10):e139-e140. PMC: 6463738. DOI: 10.2337/dc17-0403. View

17.

Polonsky W, Anderson B, Lohrer P, Aponte J, Jacobson A, Cole C . Insulin omission in women with IDDM. Diabetes Care. 1994; 17(10):1178-85. DOI: 10.2337/diacare.17.10.1178. View

18.

Weinstock R, Xing D, Maahs D, Michels A, Rickels M, Peters A . Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry. J Clin Endocrinol Metab. 2013; 98(8):3411-9. DOI: 10.1210/jc.2013-1589. View

19.

Garg S, Henry R, Banks P, Buse J, Davies M, Fulcher G . Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes. N Engl J Med. 2017; 377(24):2337-2348. DOI: 10.1056/NEJMoa1708337. View

20.

Mathieu C, Dandona P, Gillard P, Senior P, Hasslacher C, Araki E . Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial. Diabetes Care. 2018; 41(9):1938-1946. DOI: 10.2337/dc18-0623. View