Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study.
Adult
Age Factors
Aged
Diabetes Mellitus, Type 2
/ drug therapy
Diabetic Ketoacidosis
/ chemically induced
Dipeptidyl-Peptidase IV Inhibitors
/ adverse effects
Female
Humans
Hypoglycemic Agents
/ adverse effects
Male
Middle Aged
Propensity Score
Proportional Hazards Models
Retrospective Studies
Risk Factors
Sex Factors
Sodium-Glucose Transporter 2 Inhibitors
/ adverse effects
Young Adult
Journal
Annals of internal medicine
ISSN: 1539-3704
Titre abrégé: Ann Intern Med
Pays: United States
ID NLM: 0372351
Informations de publication
Date de publication:
15 09 2020
15 09 2020
Historique:
pubmed:
28
7
2020
medline:
22
12
2020
entrez:
28
7
2020
Statut:
ppublish
Résumé
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors could increase the risk for diabetic ketoacidosis (DKA). To assess whether SGLT-2 inhibitors, compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk for DKA in patients with type 2 diabetes. Population-based cohort study; prevalent new-user design between 2013 and 2018. (ClinicalTrials.gov: NCT04017221). Electronic health care databases from 7 Canadian provinces and the United Kingdom. 208 757 new users of SGLT-2 inhibitors were matched by using time-conditional propensity scores to 208 757 recipients of DPP-4 inhibitors. Cox proportional hazards models estimated site-specific hazard ratios (HRs) with 95% CIs of DKA comparing receipt of SGLT-2 inhibitors with receipt of DPP-4 inhibitors, which were pooled by using random-effects models. Secondary analyses were stratified by molecule, age, sex, and prior receipt of insulin. Overall, 521 patients were diagnosed with DKA during 370 454 person-years of follow-up (incidence rate per 1000 person-years, 1.40 [95% CI, 1.29 to 1.53]). Compared with DPP-4 inhibitors, SGLT-2 inhibitors were associated with an increased risk for DKA (incidence rate, 2.03 [CI, 1.83 to 2.25] versus 0.75 [CI, 0.63 to 0.89], respectively; HR, 2.85 [CI, 1.99 to 4.08]). Molecule-specific HRs were 1.86 (CI, 1.11 to 3.10) for dapagliflozin, 2.52 (CI, 1.23 to 5.14) for empagliflozin, and 3.58 (CI, 2.13 to 6.03) for canagliflozin. Age and sex did not modify the association; prior receipt of insulin appeared to decrease the risk. There was unmeasured confounding and no laboratory data were available for the majority of patients, and molecule-specific analyses were conducted at a limited number of sites. SGLT-2 inhibitors were associated with an almost 3-fold increased risk for DKA, with molecule-specific analyses suggesting a class effect. Canadian Institutes of Health Research.
Sections du résumé
BACKGROUND
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors could increase the risk for diabetic ketoacidosis (DKA).
OBJECTIVE
To assess whether SGLT-2 inhibitors, compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk for DKA in patients with type 2 diabetes.
DESIGN
Population-based cohort study; prevalent new-user design between 2013 and 2018. (ClinicalTrials.gov: NCT04017221).
SETTING
Electronic health care databases from 7 Canadian provinces and the United Kingdom.
PATIENTS
208 757 new users of SGLT-2 inhibitors were matched by using time-conditional propensity scores to 208 757 recipients of DPP-4 inhibitors.
MEASUREMENTS
Cox proportional hazards models estimated site-specific hazard ratios (HRs) with 95% CIs of DKA comparing receipt of SGLT-2 inhibitors with receipt of DPP-4 inhibitors, which were pooled by using random-effects models. Secondary analyses were stratified by molecule, age, sex, and prior receipt of insulin.
RESULTS
Overall, 521 patients were diagnosed with DKA during 370 454 person-years of follow-up (incidence rate per 1000 person-years, 1.40 [95% CI, 1.29 to 1.53]). Compared with DPP-4 inhibitors, SGLT-2 inhibitors were associated with an increased risk for DKA (incidence rate, 2.03 [CI, 1.83 to 2.25] versus 0.75 [CI, 0.63 to 0.89], respectively; HR, 2.85 [CI, 1.99 to 4.08]). Molecule-specific HRs were 1.86 (CI, 1.11 to 3.10) for dapagliflozin, 2.52 (CI, 1.23 to 5.14) for empagliflozin, and 3.58 (CI, 2.13 to 6.03) for canagliflozin. Age and sex did not modify the association; prior receipt of insulin appeared to decrease the risk.
LIMITATIONS
There was unmeasured confounding and no laboratory data were available for the majority of patients, and molecule-specific analyses were conducted at a limited number of sites.
CONCLUSION
SGLT-2 inhibitors were associated with an almost 3-fold increased risk for DKA, with molecule-specific analyses suggesting a class effect.
PRIMARY FUNDING SOURCE
Canadian Institutes of Health Research.
Substances chimiques
Dipeptidyl-Peptidase IV Inhibitors
0
Hypoglycemic Agents
0
Sodium-Glucose Transporter 2 Inhibitors
0
Banques de données
ClinicalTrials.gov
['NCT04017221']
Types de publication
Comparative Study
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
417-425Subventions
Organisme : CIHR
ID : DSE-146021
Pays : Canada
Investigateurs
Samy Suissa
(S)
Colin R Dormuth
(CR)
Brenda R Hemmelgarn
(BR)
Jacqueline Quail
(J)
Dan Chateau
(D)
J Michael Paterson
(JM)
Jacques LeLorier
(J)
Adrian R Levy
(AR)
Pierre Ernst
(P)
Kristian B Filion
(KB)
Lisa M Lix
(LM)
Robert W Platt
(RW)
Ingrid S Sketris
(IS)
Commentaires et corrections
Type : CommentIn