Immune checkpoints inhibitors and hyperglycemia: A Meta-analysis of randomized controlled trials.
Diabetes
Hyperglycaemia
Immune checkpoint inhibitors
Meta-analysis
Journal
Diabetes research and clinical practice
ISSN: 1872-8227
Titre abrégé: Diabetes Res Clin Pract
Pays: Ireland
ID NLM: 8508335
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
29
07
2019
revised:
17
01
2020
accepted:
05
03
2020
pubmed:
18
3
2020
medline:
28
7
2020
entrez:
18
3
2020
Statut:
ppublish
Résumé
Immune checkpoint inhibitors (ICI) exert their therapeutic effect by modulating the immune system and potentiating antitumor immunity. ICI have been associated with several immune-related adverse events, such as diabetes. However, no formal metaanalysis with this respect has been conducted so far. Aim of the present metaanalysis of randomized trials is to assess the effects of ICI on incident diabetes and hyperglycemia. A MEDLINE, Scopus, ISI-WOS, and Cochrane database search was performed to identify trials, enrolling patients with any form of cancer, up to April 23rd, 2019 in which ICI have been compared either with placebo or active comparators. Data were extracted from published reports or, if not available, from clinicaltrials.gov. The principal endpoints were the incidence of diabetes and cases of hyperglycemia, reported as adverse events. Mantel-Haenszel Odds Ratio with 95% Confidence Interval (MH-OR) was calculated for all outcomes. The study has been registered on PROSPERO website (CDR133927). Out of 42 trials retrieved, 40 reported information on incident diabetes or hyperglycemia. No association of ICI with incident diabetes (MH-OR 1.27 [0.66, 2.43], p = 0.47) was observed; whereas there was a trend toward an increased risk of hyperglycemia (MH-OR 1.45 [0.99, 2.13], p = 0.060), which reached statistical significance in sensitivity analyses and when analyzing separately placebo-controlled trials (MH-OR 1.95 [1.10, 3.49], p = 0.020). I ICI treatment is associated with an increased risk of hyperglycemia, and an increase in the risk of diabetes cannot be excluded.
Sections du résumé
BACKGROUND
BACKGROUND
Immune checkpoint inhibitors (ICI) exert their therapeutic effect by modulating the immune system and potentiating antitumor immunity. ICI have been associated with several immune-related adverse events, such as diabetes. However, no formal metaanalysis with this respect has been conducted so far. Aim of the present metaanalysis of randomized trials is to assess the effects of ICI on incident diabetes and hyperglycemia.
METHODS
METHODS
A MEDLINE, Scopus, ISI-WOS, and Cochrane database search was performed to identify trials, enrolling patients with any form of cancer, up to April 23rd, 2019 in which ICI have been compared either with placebo or active comparators. Data were extracted from published reports or, if not available, from clinicaltrials.gov. The principal endpoints were the incidence of diabetes and cases of hyperglycemia, reported as adverse events. Mantel-Haenszel Odds Ratio with 95% Confidence Interval (MH-OR) was calculated for all outcomes. The study has been registered on PROSPERO website (CDR133927).
FINDINGS
RESULTS
Out of 42 trials retrieved, 40 reported information on incident diabetes or hyperglycemia. No association of ICI with incident diabetes (MH-OR 1.27 [0.66, 2.43], p = 0.47) was observed; whereas there was a trend toward an increased risk of hyperglycemia (MH-OR 1.45 [0.99, 2.13], p = 0.060), which reached statistical significance in sensitivity analyses and when analyzing separately placebo-controlled trials (MH-OR 1.95 [1.10, 3.49], p = 0.020). I
INTERPRETATION
CONCLUSIONS
ICI treatment is associated with an increased risk of hyperglycemia, and an increase in the risk of diabetes cannot be excluded.
Identifiants
pubmed: 32179128
pii: S0168-8227(20)30365-X
doi: 10.1016/j.diabres.2020.108115
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Types de publication
Journal Article
Meta-Analysis
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
108115Informations de copyright
Copyright © 2020. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest MM has received speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi, and Novartis and research grants from Bristol Myers Squibb; LN has no conflicts of interest; ID has received speaking fees from Novonordisk; BN is presently employee of Novo Nordisk; GS has received speaking fees from Novo Nordisk, Merck Sharp & Dohme, Sanofi, Boehringer Ingelheim, Eli Lilly, Astra Zeneca, L-Nutra, Theras, Sanofi, Mundipharma, Omikron, and Novartis, and consultancy fees from Servier, Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Astra Zeneca, Merck Sharp & Dohme, Sanofi, Amgem and GlaxoSmithKline; EM has received consultancy fees from Merck and Novartis speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi, and Novartis and research grants from Merck, Novartis, and Takeda.