Peter S Hamblin1,2, Rosemary Wong3, Elif I Ekinci4,5, Spiros Fourlanos6,7, Sonali Shah8, Alicia R Jones1, Matthew J L Hare9, Genevieve L Calder10, Dilan Seneviratne Epa10, Elizabeth M George11, Rinky Giri12,13, Mark A Kotowicz11,14, Mervyn Kyi6,7, Nicole Lafontaine3, Richard J MacIsaac10,15, Brendan J Nolan4,16, David N O'Neal12,15, Debra Renouf17,18, Suresh Varadarajan16, Jennifer Wong8, Sylvia Xu17, Leon A Bach9,19. 1. Department of Endocrinology and Diabetes, Western Health, St. Albans, Victoria, Australia. 2. Department of Medicine, Western Precinct, University of Melbourne, St Albans, Victoria, Australia. 3. Department of Endocrinology and Diabetes, Eastern Health, Box Hill, Victoria, Australia. 4. Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia. 5. Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia. 6. Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, Victoria, Australia. 7. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia. 8. Department of Endocrinology and Diabetes, Monash Health, Clayton, Victoria, Australia. 9. Department of Endocrinology and Diabetes, Alfred Health, Melbourne, Victoria, Australia. 10. Department of Diabetes and Endocrinology, St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia. 11. Department of Endocrinology and Diabetes, University Hospital Geelong, Barwon Health, Geelong, Victoria, Australia. 12. Werribee Mercy Hospital, Werribee, Victoria, Australia. 13. Diabetes Technology Research Group, St. Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia. 14. School of Medicine, Faculty of Health, Deakin University, Geelong, Victoria, Australia. 15. Department of Medicine, St. Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, Victoria, Australia. 16. Department of Endocrinology and Diabetes, Northern Health, Epping, Victoria, Australia. 17. Department of Endocrinology and Diabetes, Peninsula Health, Frankston, Victoria, Australia. 18. Peninsula Clinical School, Monash University, Frankston, Victoria, Australia. 19. Department of Medicine, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Abstract
CONTEXT: Diabetic ketoacidosis (DKA) has been associated with the use of sodium glucose cotransporter 2 inhibitors (SGLT2is). OBJECTIVE: To determine the incidence, characteristics, and outcomes of DKA in SGLT2i users vs nonusers with type 2 diabetes. DESIGN: Retrospective, multicenter, controlled cohort study. SETTING: All public hospitals in Melbourne and Geelong (combined population of 5 million), Australia, from 1 September 2015 to 31 October 2017. PATIENTS: Consecutive cases of DKA that developed in the community, or during the course of hospital admission, in patients with type 2 diabetes. MAIN OUTCOME MEASURES: In SGLT2i users vs nonusers: (i) OR of DKA developing during hospital admission, and (ii) incidence of DKA. RESULTS: There were 162 cases of DKA (37 SGLT2i users and 125 non-SGLT2i users) with a physician-adjudicated diagnosis of type 2 diabetes. Of these, DKA developed during the course of inpatient admission in 14 (38%) SGLT2i users vs 2 (2%) non-SGLT2i users (OR, 37.4; 95% CI, 8.0 to 175.9; P < 0.0001). The incidence of DKA was 1.02 per 1000 (95% CI, 0.74 to 1.41 per 1000) in SGLT2i users vs 0.69 per 1000 (95% CI, 0.58 to 0.82 per 1000) in non-SGLT2i users (OR, 1.48; 95% CI, 1.02 to 2.15; P = 0.037). Fifteen SGLT2i users (41%) had peak blood glucose <250 mg/dL (14 mmol/L) compared with one (0.8%) non-SGLT2i user (P < 0.001). CONCLUSIONS: SGLT2i users were more likely to develop DKA as an inpatient compared with non-SGLT2i users. SGLT2i use was associated with a small but significant increased risk of DKA.
CONTEXT: Diabetic ketoacidosis (DKA) has been associated with the use of sodium glucose cotransporter 2 inhibitors (SGLT2is). OBJECTIVE: To determine the incidence, characteristics, and outcomes of DKA in SGLT2i users vs nonusers with type 2 diabetes. DESIGN: Retrospective, multicenter, controlled cohort study. SETTING: All public hospitals in Melbourne and Geelong (combined population of 5 million), Australia, from 1 September 2015 to 31 October 2017. PATIENTS: Consecutive cases of DKA that developed in the community, or during the course of hospital admission, in patients with type 2 diabetes. MAIN OUTCOME MEASURES: In SGLT2i users vs nonusers: (i) OR of DKA developing during hospital admission, and (ii) incidence of DKA. RESULTS: There were 162 cases of DKA (37 SGLT2i users and 125 non-SGLT2i users) with a physician-adjudicated diagnosis of type 2 diabetes. Of these, DKA developed during the course of inpatient admission in 14 (38%) SGLT2i users vs 2 (2%) non-SGLT2i users (OR, 37.4; 95% CI, 8.0 to 175.9; P < 0.0001). The incidence of DKA was 1.02 per 1000 (95% CI, 0.74 to 1.41 per 1000) in SGLT2i users vs 0.69 per 1000 (95% CI, 0.58 to 0.82 per 1000) in non-SGLT2i users (OR, 1.48; 95% CI, 1.02 to 2.15; P = 0.037). Fifteen SGLT2i users (41%) had peak blood glucose <250 mg/dL (14 mmol/L) compared with one (0.8%) non-SGLT2i user (P < 0.001). CONCLUSIONS: SGLT2i users were more likely to develop DKA as an inpatient compared with non-SGLT2i users. SGLT2i use was associated with a small but significant increased risk of DKA.
Authors: Jenny Hui Ling Chieng; Tze Kai Sia; Yao Hao Teo; Joseph Zi An Wong; Tricia Jing Ying Ng; Yao Neng Teo; Nicholas L X Syn; Robin Cherian; Yoke-Ching Lim; Ping Chai; Weiqin Lin; Raymond C C Wong; Ching-Hui Sia Journal: Med Princ Pract Date: 2022-04-04 Impact factor: 2.132