Given the current focus on the risks of hypoglycemia and the aging of the population, development of strategies to safely initiate insulin therapy in the older population becomes a clinical issue that is relevant to the daily practice of medicine. This paper reports a post-hoc analysis of the subgroup of people over the age of 65 (480 of 1818 subjects) in the DURABLE trial (assessing the DURAbility of Basal Lispro mix 25 insulin Efficacy), which was a global, multiphase study with the primary objective of comparing the efficacy, safety durability of two insulin initiation regimens: insulin lispro mix (LM25, 25% lispro, 75% insulin lispro protamine suspension ) vs. insulin glargine. Patients randomized to LM25 were started on at least 10 units twice daily and those on the basal insulin regimen started with at least 10 units once daily of insulin glargine. Both groups adjusted their insulin to try to attain target fasting glucose while the LM25 group also targeted their pre-evening-meal glucose, without hypoglycemia. During the 24-week initiation phase, HbA1c decreased more in the LM25 group, with a higher proportion attaining an A1c below 7%. Overall, the incidence of hypoglycemia was similar, with a slightly higher rate in the LM25 group (p-0.037) but no difference in rates of nocturnal hypoglycemia. More LM25 patients experienced severe hypoglycemia (11 vs 2 subjects) with the majority of it occurring in the beginning of the study, suggesting that an more intensive education may be needed at the initiation of the premixed insulin regimen. Additionally, since the SU was continued at prestudy doses, a prespecified strategy to decrease the dose may have prevented the hypoglycemia. Further studies are needed to specifically address the early aspect of insulin initiation in this population. Kittie Wyne, MD, PhD, FACE