The Impact of Frailty on the Effectiveness and Safety of Intensive Glucose Control and Blood Pressure-Lowering Therapy for People With Type 2 Diabetes: Results From the ADVANCE Trial
Research Design and Methods. Cox proportional-hazard models were used to estimate the effectiveness and safety of intensive glucose control and BP intervention according to frailty (defined as FI>0.21) status. The primary outcomes were macrovascular events and microvascular events. The secondary outcomes were all-cause mortality, cardiovascular mortality, severe hypoglycaemia, and discontinuation of BP treatment due to hypotension/dizziness.
Results. There were 11140 participants (mean age 65.8, 42.5% female, 25.7% frail). Frailty was an independent predictor of all primary outcomes and secondary outcomes. The effect of intensive glucose treatment on primary outcomes showed some evidence of attenuation in the frail: HRs for combined major macro- and micro-vascular events 1.03, 95%CI 0.90-1.19 in the frail vs 0.84, 95%CI 0.74-0.94 non-frail (p=0.02). A similar trend was observed with BP intervention. Severe hypoglycaemia rates (per 1000 person-years) were higher in the frail: 8.39 (6.15–10.63) vs. 4.80 (3.84–5.76) in non-frail (p<0.001). There was no significant difference in discontinuation of BP treatment between frailty groups.
Conclusions. It was possible to retrospectively estimate frailty in a trial population, and this FI identified those at higher risk of poor outcomes. Participants with frailty had some attenuation of benefit from intensive glucose lowering and BP lowering treatments.