Evidence map›Paper›PMID 32716707›Full record

ArticleAnnals of internal medicine2020

Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study.

Antonios Douros, Lisa M Lix, Michael Fralick, Sophie Dell'Aniello, Baiju R Shah, Paul E Ronksley, Éric Tremblay, Nianping Hu, Silvia Alessi-Severini, Anat Fisher and 4 more

2 registry-linked trialsAbstract readComparative StudyMulticenter Study
PubMed Publisher
In one paragraph

Article in Annals of internal medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT04017221. Cited by 102 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 6 pooled it
13.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04017221 completed

Safety of Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors Among Patients With Type 2 Diabetes: a Multicenter Cohort Study

Ran2018Enrolled1,249,636Registered outcomes4Posted comparisons0ConditionsDiabetes Mellitus, Type 2, Diabetic Ketoacidosis, Lower Extremity Amputation, UrosepsisArmsDipeptidyl Peptidase-4 (DPP-4) Inhibitors, Other treatment combinations, Sodium-glucose cotransporter 2 (SGLT2) inhibitors
PMID 32383792PMID 32759360other papers from this trial
Open the trial in the graph
NCT06072963 phase2recruitingstarted 2024, after this paper: background citation

Combination of Intranasal Insulin With Oral Semaglutide to Improve Cognition and Cerebral Blood Flow: a Feasibility Study

Ran2024Enrolled80Registered outcomes15Posted comparisons0ConditionsAlzheimer Disease, Metabolic Syndrome, Mild Cognitive ImpairmentArmsIntranasal insulin, Intranasal insulin placebo, semaglutide, Semaglutide placebo
PMID 36871874PMID 29687620PMID 30635783PMID 30760178PMID 30868154PMID 30917904PMID 30944040PMID 30984815PMID 31022213PMID 31189511PMID 31924562PMID 32296731other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

102 citing papers in PubMed, 6 syntheses or guidelines pooled it, 170 citations in OpenAlex.

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42 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 10 institutions in 2 countries.

Antonios DourosMcGill University and Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, Quebec, Canada, and Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany (A.D.).ORCID 0000-0002-6005-4006
Lisa M LixUniversity of Manitoba, Winnipeg, Manitoba, Canada (L.M.L.).
Michael FralickSinai Health System and University of Toronto, Toronto, Ontario, Canada (M.F.).
Sophie Dell'AnielloCentre for Clinical Epidemiology, Lady Davis Institute, Montreal, Quebec, Canada (S.D.).
Baiju R ShahUniversity of Toronto, ICES, and Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (B.R.S.).ORCID 0000-0003-3598-3628
Paul E RonksleyCumming School of Medicine, University of Calgary, Calgary, Alberta, Canada (P.E.R.).
Éric TremblayInstitut national d'excellence en santé et en services sociaux (INESSS), Quebec City, Quebec, Canada (É.T.).
Nianping HuThe Health Quality Council, Saskatoon, Saskatchewan, Canada (N.H.).
Silvia Alessi-SeveriniCollege of Pharmacy and Manitoba Centre for Health Policy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada (S.A.).
Anat FisherUniversity of British Columbia, Vancouver, British Columbia, Canada (A.F.).ORCID 0000-0001-9730-5107
Shawn C BugdenCollege of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada, and School of Pharmacy, Memorial University of Newfoundland, St John's, Newfoundland and Labrador, Canada (S.C.B.).
Pierre ErnstMcGill University and Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, Quebec, Canada (P.E., K.B.F.).ORCID 0000-0001-9983-3608
Kristian B FilionMcGill University and Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, Quebec, Canada (P.E., K.B.F.).
Canadian Network for Observational Drug Effect Studies (CNODES) Investigators
McGill University · CAUniversity of Manitoba · CAInstitut National d'Excellence en Santé et en Services Sociaux · CAJewish General Hospital · CAMemorial University of Newfoundland · CASaskatchewan Health Quality Council · CASunnybrook Health Science Centre · CAUniversity of British Columbia · CAUniversity of Calgary · CAUniversity of Toronto · CA

Funding

CIHR DSE-146021
6 · The paper itself

Abstract

backgroundSodium-glucose cotransporter-2 (SGLT-2) inhibitors could increase the risk for diabetic ketoacidosis (DKA).

objectiveTo 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.

designPopulation-based cohort study; prevalent new-user design between 2013 and 2018. (ClinicalTrials.gov: NCT04017221).

settingElectronic 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.

resultsOverall, 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.

conclusionSGLT-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.

Indexed as

AdultAgedAge FactorsDiabetes Mellitus, Type 2Diabetic KetoacidosisDipeptidyl-Peptidase IV InhibitorsFemaleHumansHypoglycemic AgentsMaleMiddle AgedPropensity ScoreProportional Hazards ModelsRetrospective StudiesRisk FactorsSex FactorsDipeptidyl-Peptidase IV InhibitorsHypoglycemic AgentsSodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID32716707
OpenAlexW3046159964

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.