TY - JOUR
T1 - SGLT2 Inhibitors Increase the Risk of Diabetic Ketoacidosis Developing in the Community and during Hospital Admission
AU - Hamblin, Peter S.
AU - Wong, Rosemary
AU - Ekinci, Elif I.
AU - Fourlanos, Spiros
AU - Shah, Sonali
AU - Jones, Alicia R.
AU - Hare, Matthew J.L.
AU - Calder, Genevieve L.
AU - Epa, Dilan Seneviratne
AU - George, Elizabeth M.
AU - Giri, Rinky
AU - Kotowicz, Mark A.
AU - Kyi, Mervyn
AU - Lafontaine, Nicole
AU - Macisaac, Richard J.
AU - Nolan, Brendan J.
AU - O'Neal, David N.
AU - Renouf, Debra
AU - Varadarajan, Suresh
AU - Wong, Jennifer
AU - Xu, Sylvia
AU - Bach, Leon A.
N1 - Funding Information:
Disclosure Summary: E.I.E. is an investigator in FIGARO, FIDELIO, Rainbow, T1DGKT137831, and SCORED clinical trials. S.S. has received an educational travel grant from Novo Nordisk. A.R.J. has received an educational travel grant from Novo Nordisk. D.S.E. has received an educational travel grant from Novo Nordisk and meeting registration fee support from Merck Sharp & Dohme. E.M.G. has received an educational travel grant from Novo Nordisk. M.A.K. has received speaker fees from Astra Zeneca, Boehringer Ingelheim, Sanofi, and Novo Nordisk and travel support from Novo Nordisk. R.J.M. has receivedresearchgrantsfromNovoNordisk,Servier,Medtronic, and Grey Innovation. He has received honoraria for lectures from Eli Lilly, Novo Nordisk, Sanofi, Astra Zeneca, Merck Sharp & Dohme, Novartis, and Boehringer Ingelheim and is on the Advisory Boards of the Boehringer Ingelheim–Eli Lilly Diabetes Alliance and Astra Zeneca. He has received travel support from Novo Nordisk, Sanofi, Boehringer Ingelheim, and Astra Zeneca. He has also been a principal investigator for industry-sponsored clinical trials run by Novo Nordisk, Bayer, Janssen, and Abbive. D.N.O. reports Advisory Boards and receiving research support from Sanofi, Novo Nordisk, Abbott, and Medtronic and travel support from Novo Nordisk and Merck Sharp & Dohme. D.R. has received honoraria for talks from Astra Zeneca and Boehringer Ingelheim. S.V. has received honoraria for talks from Astra Zeneca. J.W. has received honoraria for talks from Astra Zeneca, Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Sanofi, and Merck Sharp & Dohme. She has also received a regional support grant from Novo Nordisk. S.X. has received educational travel grants from Novo Nordisk and Merck Sharp & Dohme. L.A.B. was an investigator in DECLARE. The remaining authors have nothing to disclose.
Publisher Copyright:
© 2019 Endocrine Society.
PY - 2019/6/19
Y1 - 2019/6/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85068140684&partnerID=8YFLogxK
U2 - 10.1210/jc.2019-00139
DO - 10.1210/jc.2019-00139
M3 - Article
C2 - 30835263
AN - SCOPUS:85068140684
SN - 0021-972X
VL - 104
SP - 3077
EP - 3087
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 8
ER -