Trends in second-line glucose-lowering therapy initiations and treatment outcomes across age and frailty groups in people with type 2 diabetes: UK population-based study, 2019-2024

ABSTRACT Objective To assess contemporary UK population-level trends in second-line glucose-lowering therapy initiation and explore treatment outcome trends across age and frailty groups in people with type 2 diabetes (T2D). Methods We studied 117,064 adults with T2D who initiated major second-line glucose-lowering drug classes after metformin between 2019–2024 in population-representative UK data (Clinical Practice Research Datalink). Outcomes were assessed in three groups: age ≤70 years (n=84,589 [72%]), non-frail >70 years (n=18,933 [16%]), and frail >70 years (n=13,524 [12%]), with frailty specified as an electronic frailty index ≥ 0.24. Annual prescribing trends were calculated as the proportion of each drug class among all second-line initiations. We evaluated 12-month changes in HbA 1c , weight, treatment discontinuation, and complications, including composite severe diabetes-related complications, heart failure and kidney failure. Trends were estimated using multivariable regression models adjusted for demographic and clinical characteristics. Results Use of SGLT2-inhibitors increased from 26% of overall second-line initiations in 2019 to 63% in 2024, with the greatest increase among frail adults >70 (6% in 2019 vs 60% in 2024). DPP4-inhibitor use declined substantially over the same period (44% 2019 vs 16% in 2024). In adults aged ≤70 years, mean 12-month HbA 1c response improved from -11.3 mmol/mol (95%CI -11.6 to -11.0) in 2019 to -12.9 mmol/mol (95%CI -13.2 to -12.6) in 2023, and mean weight loss improved from -1.7 kg (95%CI -1.8 to -1.5) to -2.8 kg (95%CI -2.9 to -2.6). Treatment discontinuation within 12 months remained stable (30.2% [95%CI 29.4 to 31.0] in 2019 vs 30.7% [95%CI 30.0 to 31.4] in 2022). There was limited evidence of change in short-term complications over 2019-2022: rates (per 1,000 person-years) of severe diabetes-related complications were 9.9 (95%CI 8.1 to 11.7) vs 8.6 (95%CI 6.9 to 10.3), heart failure 2.0 (95%CI 1.1 to 2.9) vs 2.7 (95%CI 1.8 to 3.7), and kidney failure 2.1 (95%CI 1.1 to 3.0) vs 1.2 (95%CI 0.5 to 1.8). All trends were consistent in adults >70, including those with frailty. Conclusion Use SGLT2-inhibitors in people with T2D has rapidly increased in the UK over 2019–2024 to represent the majority of second-line initiations, with a 10-fold increase in initiations amongst older adults with frailty. Over the same period, population-level benefits for HbA 1c and weight were modest, with no evidence of changes in risk of short-term discontinuation or diabetes complications. Findings support the careful use of SGLT2i across the wider population with type 2 diabetes including frail older adults.