Background
Once-weekly dulaglutide (1.5 mg or 0.75 mg) was well tolerated and improved glycemic control with comparable efficacy in patients with type 2 diabetes (T2D) aged ≥65 years and <65 years in the AWARD-2 (Assessment of Weekly AdministRation of LY2189265 [dulaglutide] in Diabetes-2) clinical trial; however, composite endpoints combining efficacy and safety in the elderly population were not explored.

Aims
This post hoc analysis of the AWARD-2 trial assessed the effect of dulaglutide 1.5 mg and 0.75 mg versus insulin glargine on composite endpoints consisting of the percentages of elderly patients (aged ≥65 years) with T2D achieving a glycated hemoglobin (HbA1c) <7.5% without documented symptomatic or nocturnal hypoglycemia at 52 weeks.

Methods
Patients aged ≥65 years in each treatment group (dulaglutide 1.5 mg, dulaglutide 0.75 mg, or glargine) were identified. Logistic regression was used to analyze the following composite endpoints: 1) patients achieving HbA1c<7.5% (58 mmol/mol) without documented symptomatic hypoglycemia, and 2) patients achieving HbA1c<7.5% without nocturnal hypoglycemia. Hypoglycemia was defined as plasma glucose ≤70 mg/dL (≤3.9 mmol/L). Exploratory analyses were also performed for percentages of patients achieving HbA1c<8% (64 mmol/mol) at 52 weeks without either documented symptomatic or nocturnal hypoglycemia. 

Results
Overall, a total of 161 of 807 (20%) patients were aged ≥65 years (n=54 dulaglutide 1.5 mg, n=51 dulaglutide 0.75 mg, n=56 glargine) in AWARD-2. Baseline HbA1c (mean±SD) in the elderly was 8.1±1.0%. The percentage of elderly patients who achieved the composite endpoint of HbA1c<7.5% without documented symptomatic hypoglycemia was 48.0%, 33.3%, and 33.3% for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and glargine patients, respectively (Table). The odds of achieving this composite endpoint were greater for the dulaglutide 1.5 mg group than for the glargine group. The percentage of patients who achieved the composite endpoint of HbA1c<7.5% without nocturnal hypoglycemia was 60.0%, 45.1%, and 27.8% for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and glargine patients, respectively. The odds of achieving this composite endpoint were greater for the dulaglutide 1.5 mg and dulaglutide 0.75 mg groups than for the glargine group. Similar results were observed for HbA1c<8.0%. In addition, results were similar in direction and magnitude for patients aged <65 years. The safety profile of dulaglutide in the elderly was generally similar to the overall population in AWARD-2, with the most common adverse events being gastrointestinal in nature.

Discussion
Composite endpoints that include both efficacy and safety are useful to explore in the elderly population. An HbA1c goal of <7.5% and a hypoglycemia limit of ≤70 mg/dL were chosen as targets appropriate for the elderly population. In this post hoc analysis, greater percentages of elderly patients treated with dulaglutide 1.5 mg achieved HbA1c<7.5% without nocturnal hypoglycemia and HbA1c<7.5% without documented symptomatic hypoglycemia compared to those treated with insulin glargine. In addition, greater percentages of elderly patients treated with dulaglutide 0.75 mg achieved HbA1c<7.5% without nocturnal hypoglycemia compared to those treated with insulin glargine. In the AWARD-2 study, which compared 2 injectable therapies (dulaglutide and insulin glargine) for the treatment of T2D, these findings support dulaglutide as a potential first injectable therapy option in the vulnerable, elderly population.

A higher percentage of elderly on dulaglutide achieved hba1c&lt;7.5% without nocturnal hypoglycemia vs. glargine in AWARD-2

A higher percentage of elderly on dulaglutide achieved hba1c<7.5% without nocturnal hypoglycemia vs. glargine in AWARD-2