Frailty-Informed Deprescribing of Glucose-Lowering Therapy in Older Adults with Type 2 Diabetes: A Pragmatic Clinical...

Older adults with type 2 diabetes are often subjected to intensive glucose-lowering therapies with a high likelihood of hypoglycaemia, falls, functional decline, and treatment burden. While international recommendations advocate for individualised glycaemic targets, they provide little clarification on when, or how, to de-intensify therapies as health status changes.

We undertook a targeted evidence synthesis of randomised controlled trials, observational cohort studies, target trial emulation studies, and international clinical guidelines focusing on glucose-lowering agents for the treatment of diabetes mellitus in patients aged 65 years and older. Evidence was synthesised and prioritised based on relevance for the important outcomes in later life, including hypoglycaemia, hospitalisation, functional decline, quality of life, and mortality. From this evidence and the principles of geriatric medicine, we constructed a pragmatic, frailty-informed clinical decision framework for the purposes of guiding deprescribing and the de-intensification of glucose-lowering therapy.

Older adults in a variety of care continuum settings, particularly with frailty, multimorbidity, cognitive impairment, or a limited life expectancy, tend to stay on intensive glucose-lowering therapies for very little, if any, benefit. Target trial emulation studies and observational studies most often show that hypoglycaemia and treatment burden are lowered by de-intensifying high-risk medications, particularly insulin and sulfonylureas, without any clinically important deterioration in glycaemic control. Even with the evidence, existing guidance lacks a practical operational framework to implement such evidence in everyday clinical practice.

We suggest a frailty-informed clinical decision framework that integrates functional status, physiologic vulnerability, treatment-related risks, and patient preferences in making glucose-lowering treatment decisions in older adults with type 2 diabetes. This framework shifts the focus to patient safety and functional outcomes, instead of HbA1c targets, to provide a practical approach to deprescribing and de-intensifying treatment to minimise iatrogenic harm and, most importantly, to align care with the preferences of older adults.