Frailty in randomized controlled trials of glucose-lowering therapies for type 2 diabetes: An individual participant data meta-analysis of frailty prevalence, treatment efficacy, and adverse events
Frailty was uncommon in these trials, and participants with a high degree of frailty were rarely included. Frailty is associated very modest attenuation of treatment efficacy for glycaemic outcomes and with greater incidence of both adverse events and MACE independent of treatment allocation. While these findings are compatible with calls to relax HbA1c-based targets in people living with frailty, they also highlight the need for inclusion of people living with frailty in trials. This would require changes to trial processes to facilitate the explicit assessment of frailty and support the participation of people living with frailty. Such changes are important as the absolute balance of risks and benefits remains uncertain among those with higher degrees of frailty, who are largely excluded from trials.
Authors
- Andrew Paul Clegg (ORCID: https://orcid.org/0000-0001-5972-1097)
- Kenneth J. Rockwood (ORCID: https://orcid.org/0000-0002-6674-995X)
- Miles D. Witham (ORCID: https://orcid.org/0000-0002-1967-0990)
- David Phillippo (ORCID: https://orcid.org/0000-0003-2672-7841)
- Lili Wei (ORCID: https://orcid.org/0000-0002-3255-3449)
- David McAllister (ORCID: https://orcid.org/0000-0003-3550-1764)
- Nicky J. Welton (ORCID: https://orcid.org/0000-0003-2198-3205)
- Elaine Butterly (ORCID: https://orcid.org/0000-0001-9410-0237)
- Sofia Dias (ORCID: https://orcid.org/0000-0002-2172-0221)
- Ryan McChrystal (ORCID: https://orcid.org/0000-0003-1513-6966)
- Amanda Adler (ORCID: https://orcid.org/0000-0002-2797-3385)
- Peter Hanlon (ORCID: https://orcid.org/0000-0002-5828-3934)
- Heather Wightman
- Naveed A. Sattar (ORCID: https://orcid.org/0000-0002-1604-2593)
Institutions
- Dalhousie University (CA)
- University of Leeds (GB)
- Cumbria Northumberland Tyne and Wear NHS Foundation Trust (GB)
- Nova Scotia Health Authority (CA)
- University of Bristol (GB)
- University of Oxford (GB)
- Oxford Centre for Diabetes, Endocrinology and Metabolism (GB)
- NIHR Newcastle Biomedical Research Centre (GB)
- Bradford Teaching Hospitals NHS Foundation Trust (GB)
- University of York (GB)
- University of Glasgow (GB)
Publication Details
- Journal
- PLoS Medicine
- Published
- 2025-04-07
- DOI
- https://doi.org/10.1371/journal.pmed.1004553
- Citations
- 10
- Primary Topic
- Frailty in Older Adults
- Type
- article
- Field-Weighted Citation Impact
- 12.24
Funders
- Medical Research Council