Sodium-glucose cotransporter-2 inhibitors (SGLT2) in frail or older people with type 2 diabetes and heart failure: a systematic review and meta-analysis

Aldafas, Rami; Crabtree, Tomas; Alkharaiji, Mohammed; Vinogradova, Yana; Idris, Iskandar

Abstract

Objective: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear. Methods: We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model. Results: We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference −0.13, 95%CI: −0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: −0.69 to 0.95), cardiac death (RR 0.80, 95%CI: −0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59–0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis. Conclusions: In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.

• Journal Article Type: Article
• Acceptance Date: Nov 14, 2023
• Online Publication Date: Jan 29, 2024
• Publication Date: 2024-01
• Deposit Date: Feb 7, 2024
• Publicly Available Date: Feb 7, 2024
• Journal: Age and Ageing
• Print ISSN: 0002-0729
• Electronic ISSN: 1468-2834
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 53
• Issue: 1
• Article Number: afad254
• DOI: https://doi.org/10.1093/ageing/afad254
• Keywords: sodium-glucose cotransporter 2 inhibitors, frail, older, type 2 diabetes, heart failure, systematic review, older people
• Public URL: https://nottingham-repository.worktribe.com/output/31151219
• Publisher URL: https://academic.oup.com/ageing/article/53/1/afad254/7591145
• Additional Information: © The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society.; ; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.