Perindopril/Indapamide

To compare the vascular effects of pursuing more versus less glucose lowering in patients with younger or older age at diabetes diagnosis, and with shorter or longer diabetes duration.

We studied 11,138 participants from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, classified into subgroups defined by age at diabetes diagnosis (≤50, >50–60, and >60 years) and diabetes duration (≤5, >5–10, and >10 years).

Intensive glucose lowering significantly lowered the risk of the primary composite outcome of major macrovascular and microvascular events (hazard ratio 0.90, 95% CI 0.82–0.98) with no evidence of heterogeneity in the proportional effects across subgroups defined by age at diagnosis or diabetes duration (P for heterogeneity = 0.86 and 0.47, respectively). Similar consistent treatment effects were also observed for all-cause death, cardiovascular death, and the components of major vascular events.

Intensive glucose lowering may be recommended irrespective of age at diagnosis or diabetes duration.

With population ageing, drug trials are increasingly turning their attention to including older, frailer people. This review aimed to provide an overview of how frailty was assessed in published studies related to clinical pharmacological trials, and on the interaction of frailty on the efficacy of the treatments. We searched MEDLINE, EMBASE and Cochrane for clinical drug trials in older people. A total of 4031 abstracts were screened and 17 relevant studies were included in this review. We summarized the findings of these 17 trials into five main clinical areas: cardiovascular (eight studies), cognition (one study), vaccination (two studies), cancer (four studies) and other (two studies). Frailty was assessed retrospectively in most of the studies. Frailty was treated as an ordinal variable (with different levels of frailty) or binary variable (frail/non‐frail) using cut‐offs in some studies, and as a continuous in some other studies. The effect of frailty on the treatment efficacy was not consistent among the studies. While several trials, such as the Action in Diabetes and Vascular Disease—Preterax and Diamicron Modified Release Controlled Evaluation trials, the Systolic Blood Pressure Intervention Trial and the Aspirin in Reducing Events in the Elderly trial, showed some reduced effects of the treatment in frail patients, most of the trials showed that the benefits of the treatment are not affected by frailty. Some trials even showed that the benefits of the treatment were more significant in frailer patients (the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure and the Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure trials). The results of this review suggest that routine measurement of frailty in participants in clinical drug trials would improve our knowledge of the effect of treatment in the frail and identify those who have more or least to gain from treatment.