The effect of canagliflozin on amputation risk in the CANVAS program and the CREDENCE trial.
antidiabetic drug
Journal
Diabetes, obesity & metabolism
ISSN: 1463-1326
Titre abrégé: Diabetes Obes Metab
Pays: England
ID NLM: 100883645
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
15
03
2020
revised:
07
05
2020
accepted:
17
05
2020
pubmed:
22
5
2020
medline:
25
6
2021
entrez:
22
5
2020
Statut:
ppublish
Résumé
To determine whether there was an explanation as to why the effects of the sodium-glucose co-transporter-2 (SGLT2) inhibitor canagliflozin on amputation risk vary between the CANVAS program and the CREDENCE trial. We performed a pooled analysis of patient-level data from the CANVAS program and the CREDENCE trial. Patient characteristics associated with amputation risk were assessed in univariable and multivariable regression models and compared between studies. Effects of canagliflozin on amputation risk were determined from Cox proportional hazards models and compared between studies, subgroups and for a range of amputation outcomes. Effects over time were explored by cumulative event curves. In the CANVAS program (n = 10 142; median follow-up 2.4 years) and CREDENCE trial (n = 4401; median follow-up 2.5 years), 2.3% and 5.3% of participants, respectively, reported baseline amputation history. Key differences at baseline were the proportions with nephropathy (CREDENCE higher, 100% vs. 17.5%) and cardiovascular disease (CANVAS higher, 66% vs. 50%). There were 133 amputations in CREDENCE (3.0% annual event rate) and 187 amputations in CANVAS (1.8% annual event rate), with prior amputation being the strongest predictor of future amputation in both groups. Effects of canagliflozin on amputation risk were significantly different between trials (P We identified no explanation for the difference in amputation risk between the CREDENCE trial and the CANVAS program. In the context of null effects of SGLT2 inhibition on amputation in CREDENCE and all other large trials, there is a possibility that the finding in CANVAS was the result of chance.
Substances chimiques
Sodium-Glucose Transporter 2
0
Sodium-Glucose Transporter 2 Inhibitors
0
Canagliflozin
0SAC974Z85
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1753-1766Subventions
Organisme : These studies were supported by Janssen Research & Development, LLC.
Pays : International
Informations de copyright
© 2020 John Wiley & Sons Ltd.
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