Glucose-lowering drugs or strategies, atherosclerotic cardiovascular events, and heart failure in people with or at risk of type 2 diabetes: an updated systematic review and meta-analysis of randomised cardiovascular outcome trials.

Aged Atherosclerosis / prevention & control Diabetes Mellitus, Type 2 / complications Glucagon-Like Peptide-1 Receptor / agonists Heart Failure / prevention & control Humans Hypoglycemic Agents / therapeutic use Middle Aged Sodium-Glucose Transporter 2 Inhibitors / therapeutic use

Journal

The lancet. Diabetes & endocrinology
ISSN: 2213-8595
Titre abrégé: Lancet Diabetes Endocrinol
Pays: England
ID NLM: 101618821

Informations de publication

Date de publication:
05 2020
Historique:
received: 16 08 2019
revised: 27 01 2020
accepted: 28 01 2020
pubmed: 26 4 2020
medline: 18 7 2020
entrez: 26 4 2020
Statut: ppublish

Résumé

In our 2015 systematic review and meta-analysis of cardiovascular outcome trials for glucose-lowering drugs or strategies in people with or at risk of type 2 diabetes, we reported a modest reduction in atherosclerotic cardiovascular events and an increased risk of heart failure, but with heterogeneous effects by drug or intervention type. In view of the completion of many large cardiovascular outcome trials since our previous analysis, including trials of novel drugs that have shown beneficial effects on cardiovascular outcomes, we aimed to update our analysis to incorporate these findings. We did an updated systematic review and meta-analysis of large cardiovascular outcome trials of glucose-lowering drugs or strategies in people with or at risk of type 2 diabetes. We searched Ovid MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials databases for reports of trials published from Nov 15, 2013 to Nov 20, 2019. We included randomised controlled trials with a minimum of 1000 adults (aged ≥19 years) with or at risk of type 2 diabetes, with major adverse cardiovascular events (MACE) as an outcome, and with follow-up of at least 12 months. We excluded trials with patients enrolled with an acute cardiovascular event. The main outcomes of interest were MACE (generally defined as a composite of cardiovascular death, myocardial infarction, or stroke) and heart failure. We calculated pooled risk ratios (RRs) and 95% CIs with inverse-variance random-effects models, did meta-regression to analyse treatment effects per difference in bodyweight achieved, and explored results stratified by baseline subgroups. Our updated search yielded 30 eligible trials (n=225 305). The mean age of participants was 63·0 years (SD 8·4) and mean duration of diabetes was 9·4 years (6·6). After a mean follow-up of 3·8 years (1·8), 23 016 (10·2%) participants had MACE and 8169 (3·6%) had a heart failure event. Glucose-lowering drugs or strategies lowered the risk of MACE compared with standard care or placebo (RR 0·92, 95% CI 0·89-0·95, p<0·0001), with no overall effect on the risk of heart failure (0·98, 0·90-1·08, p=0·71). However, across drug classes or strategies, the magnitude and directionality of RR for heart failure varied (p Glucose-lowering drugs or strategies overall reduced the risk of fatal and non-fatal atherosclerotic events. The effect on heart failure was neutral overall but varied substantially by intervention type, with interventions associated with weight loss showing a beneficial effect. The cardiovascular and heart failure benefits of interventions associated with weight loss might extend to patients without established cardiovascular disease. None.

Sections du résumé

BACKGROUND
In our 2015 systematic review and meta-analysis of cardiovascular outcome trials for glucose-lowering drugs or strategies in people with or at risk of type 2 diabetes, we reported a modest reduction in atherosclerotic cardiovascular events and an increased risk of heart failure, but with heterogeneous effects by drug or intervention type. In view of the completion of many large cardiovascular outcome trials since our previous analysis, including trials of novel drugs that have shown beneficial effects on cardiovascular outcomes, we aimed to update our analysis to incorporate these findings.
METHODS
We did an updated systematic review and meta-analysis of large cardiovascular outcome trials of glucose-lowering drugs or strategies in people with or at risk of type 2 diabetes. We searched Ovid MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials databases for reports of trials published from Nov 15, 2013 to Nov 20, 2019. We included randomised controlled trials with a minimum of 1000 adults (aged ≥19 years) with or at risk of type 2 diabetes, with major adverse cardiovascular events (MACE) as an outcome, and with follow-up of at least 12 months. We excluded trials with patients enrolled with an acute cardiovascular event. The main outcomes of interest were MACE (generally defined as a composite of cardiovascular death, myocardial infarction, or stroke) and heart failure. We calculated pooled risk ratios (RRs) and 95% CIs with inverse-variance random-effects models, did meta-regression to analyse treatment effects per difference in bodyweight achieved, and explored results stratified by baseline subgroups.
FINDINGS
Our updated search yielded 30 eligible trials (n=225 305). The mean age of participants was 63·0 years (SD 8·4) and mean duration of diabetes was 9·4 years (6·6). After a mean follow-up of 3·8 years (1·8), 23 016 (10·2%) participants had MACE and 8169 (3·6%) had a heart failure event. Glucose-lowering drugs or strategies lowered the risk of MACE compared with standard care or placebo (RR 0·92, 95% CI 0·89-0·95, p<0·0001), with no overall effect on the risk of heart failure (0·98, 0·90-1·08, p=0·71). However, across drug classes or strategies, the magnitude and directionality of RR for heart failure varied (p
INTERPRETATION
Glucose-lowering drugs or strategies overall reduced the risk of fatal and non-fatal atherosclerotic events. The effect on heart failure was neutral overall but varied substantially by intervention type, with interventions associated with weight loss showing a beneficial effect. The cardiovascular and heart failure benefits of interventions associated with weight loss might extend to patients without established cardiovascular disease.
FUNDING
None.

Identifiants

DOI: 10.1016/S2213-8587(20)30038-3 PMID: 32333878
pubmed: 32333878
pii: S2213-8587(20)30038-3
doi: 10.1016/S2213-8587(20)30038-3
pii:
doi:

Substances chimiques

Glucagon-Like Peptide-1 Receptor 0
Hypoglycemic Agents 0
Sodium-Glucose Transporter 2 Inhibitors 0

Types de publication

Journal Article Meta-Analysis Research Support, Non-U.S. Gov't Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

418-435

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Auteurs

Olivia R Ghosh-Swaby (OR)

Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; Women's College Research Institute and Cardiovascular Division, Women's College Hospital, Toronto, ON, Canada.

Shaun G Goodman (SG)

Department of Medicine, St Michael's Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada.

Lawrence A Leiter (LA)

Department of Medicine, St Michael's Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.

Alice Cheng (A)

Department of Medicine, St Michael's Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Credit Valley Hospital, Mississauga, ON, Canada.

Kim A Connelly (KA)

Department of Medicine, St Michael's Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada.

David Fitchett (D)

Department of Medicine, St Michael's Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.

Peter Jüni (P)

Department of Medicine, University of Toronto, Toronto, ON, Canada; Applied Health Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada.

Michael E Farkouh (ME)

Department of Medicine, University of Toronto, Toronto, ON, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.

Jacob A Udell (JA)

Women's College Research Institute and Cardiovascular Division, Women's College Hospital, Toronto, ON, Canada; Department of Medicine, St Michael's Hospital, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada. Electronic address: jay.udell@utoronto.ca.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Glucose-lowering drugs or strategies,...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Artériopathies oblitérantes › Artériosclérose › Athérosclérose › Glucose-lowering drugs or strategies,...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › Glucose-lowering drugs or strategies,...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur hormone gastrointestinale › Récepteurs des peptides similaires au glucagon › Récepteur du peptide-1 similaire au glucagon › Glucose-lowering drugs or strategies,...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Défaillance cardiaque › Glucose-lowering drugs or strategies,...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Glucose-lowering drugs or strategies,...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Glucose-lowering drugs or strategies,...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Glucose-lowering drugs or strategies,...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Inhibiteurs du cotransporteur sodium-glucose de type 2 › Glucose-lowering drugs or strategies,...