Initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to level of frailty in people with type 2 diabetes and cardiovascular disease in Denmark: a cross-sectional, nationwide study.

Background: Whether frailty influences the initiation of two cardioprotective diabetes drug therapies (ie, SGLT2 inhibitors and GLP-1 receptor agonists) in people with type 2 diabetes and cardiovascular disease is unknown. We aimed to assess rates of initiation of SGLT2 inhibitors and GLP-1 receptor agonists according to frailty in people with type 2 diabetes and cardiovascular disease.
Methods: For this cross-sectional, nationwide study, all people with type 2 diabetes and cardiovascular disease in Denmark between Jan 1, 2015, and Dec 31, 2021, from six Danish health-data registers were identified. People younger than 40 years, with end-stage renal disease, with registered contraindications to SGLT2 inhibitors or GLP-1 receptor agonists, or with previous use of either drug therapy were excluded. The Hospital Frailty Risk Score was used to categorise people as either non-frail, moderately frail, or severely frail. Cox proportional hazards models were used to analyse the association between frailty and initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist.
Findings: Of 119 390 people with type 2 diabetes and cardiovascular disease, 103 790 were included. Median follow-up time was 4·5 years (IQR 2·7-6·1) and median age across the three frailty groups was 71 years (64-79). 65 959 (63·6%) of 103 790 people were male and 37 831 (36·5%) were female. At index date, 66 910 (64·5%) people were non-frail, 29 250 (28·2%) were moderately frail, and 7630 (7·4%) were severely frail. Frailty was associated with a significantly lower probability of initiating therapy with an SGLT2 inhibitor or a GLP-1 receptor agonist than in people who were non-frail (moderately frail hazard ratio 0·91, 95% CI 0·88-0·94, p<0·0001; severely frail 0·75, 0·70-0·80, p<0·0001). This association persisted after adjustment for age, sex, socioeconomic status, year of inclusion, duration of type 2 diabetes, duration of cardiovascular disease, polypharmacy, and comorbidity.
Interpretation: In people with type 2 diabetes and cardiovascular disease in Denmark, frailty was associated with a significantly lower probability of SGLT2-inhibitor or GLP-1 receptor-agonist initiation, despite their benefits. Formulating clear and updated guidelines on the use of SGLT2 inhibitors and GLP-1 receptor agonists in people who are frail with type 2 diabetes and cardiovascular disease should be a priority.
Funding: Department of Cardiology, Herlev and Gentofte University Hospital.
Translation: For the Danish translation of the abstract see Supplementary Materials section.
Competing Interests: Declaration of interests MEM receives grants from the CARDIO-HGH Foundation, Herlev and Gentofte University Hospital, and the Danish Cardiovascular Academy. MS receives lecture fees from Novartis, Boehringer Ingelheim, AstraZeneca, and Novo Nordisk. ACF receives grants from Steno Diabetes Center Sjaelland, Region Sjælland Den Sundhedsvidenskabelige Forskningsfond, and Murermester Lauritz Peter Christensen og Hustru Kirsten Sigrid Christensens Fond. JHB participates on an advisory board for Bayer. JJ receives grants from The Danish Heart Foundation and the CARDIO-HGH Foundation; receives payment and honoraria for lectures, presentations, and manuscript writing from Boehringer Ingelheim; and participates on advisory boards for AstraZeneca and Boehringer Ingelheim. JES receives grants from Herlev-Gentofte Forskningsfond, Snedkermester Sophus Jacobs; Torben og Alice Frimodts Fond; Dagmar Marshalls Fond; and Eva og Henry Frænkels Mindefond. LK receives speaker honoraria from Novo Nordisk, AstraZeneca, Novartis, and Boehringer Ingelheim. MCP receives grants and contracts from Boehringer Ingelheim, Roche, SQ Innovation, AstraZeneca, Novartis, Novo Nordisk, and Pharmacosmos; receives consulting fees from Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Takeda, Corvia, Cardiorentis, Pharmacosmos, Siemens, and Vifor; receives payment or honoraria for lectures, presentations, manuscript writing, or educational events from Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Takeda, Corvia, Cardiorentis, Pharmacosmos, Siemens, and Vifor; participates on a data safety monitoring board and advisory board for Takeda and Taikoku; and is the Director of Global Clinical Trials Partners. NS receives grants and contracts from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics; receives consulting fees from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; and receives fees for lectures or manuscript writing from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, and Novo Nordisk. JJVM receives payment or honoraria for lectures, presentations, speaker bureaus, or manuscript writing from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, Medscape, Herat.org, ProAdWise, Servier, and the Corpus. JJVM receives payment for participating on advisory boards for Cytokinetics, Amgen, AstraZeneca, Theracos, Ionis Pharmaceuticals, DalCor, Cardurion, Novartis, GlaxoSmithKline, Bayer, KBP Biosciences, Boehringer Ingelheim, and Bristol Myers Squibb. All other authors declare no competing interests.
(Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)