Association between hypoglycaemic drug de-intensification, mortality and hospital admission in older adults with type 2 diabetes: a cohort study emulating a target trial

Background Hypoglycaemic drugs (sulfonylureas, glinides or insulins) are commonly prescribed for older adults with type 2 diabetes (T2D) but may carry risks of adverse events. Whether de-intensifying hypoglycaemic drugs is associated with clinical benefit in older adults remains unknown. Objective To evaluate the association between de-intensification of hypoglycaemic drugs and clinical outcomes in older adults with T2D. Methods Cohort study conducted with the target trial emulation approach, using data collected from 2000 French general practises between January 2010 and February 2019 (The Health Improvement Network—THIN database). Eligible participants were ≥75 years old, on stable hypoglycaemic drugs (no change in drug or dose) for at least 6 months, and had an HbA1c value <9%. Hypoglycaemic drug de-intensification (exposure) was defined as cessation or reduction of ≥50% of total dose. The primary outcome was a composite measure of all-cause death or hospital admissions within 3 months, and its association with exposure was assessed using multivariable logistic regression adjusted for potential baseline confounders. Results The study included 14 383 unique individuals corresponding to 177 314 trial emulation participants (mean age 80 years; 44.7% female). Of these, 6480 participants were allocated to de-intensification group, and 170 834 to the control group. At 3 months, the primary outcome occurred in 3.96% of the de-intensification group and 2.99% of controls [adjusted relative risk, 1.33 (95% CI, 1.22–1.43)]. Subgroup analyses showed consistent associations across most participants’ profiles. Conclusions In older adults with T2D, de-intensification of hypoglycaemic drugs was associated with a higher short-term risk of all-cause death or hospitalisation.