Efficacy and Safety of Insulin Glargine 300 U/mL in North Americans and Non-North Americans with Type 2 Diabetes: A Patient-Level Meta-Analysis of the EDITION 1, 2 and 3 Studies

Objective: To assess efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus (vs) insulin glargine 100 U/mL (Gla-100) in North American and non-North American people with type 2 diabetes mellitus on different background therapies. Methods: A patient-level meta-analysis of three international studies (EDITION 1, 2 and 3) was performed to examine glycemic control and hypoglycemia over 6 months in 2496 participants including 1420 participants in a North American sub-population (Gla-300, N=700; Gla-100, N=720). Endpoints included change in glycated hemoglobin (HbA1c), percentage of patients at target HbA1c at Month 6, incidence and rate of hypoglycemic events, change in body weight and insulin dose, as well as incidence of adverse events. Results: Mean change in HbA1c was comparable for Gla-300 and Gla-100 in both regions (P=0.8347 for treatment-by-subgroup interaction). There were no regional differences in the percentage of participants achieving target HbA1c <7% (53.0 mmol/mol) or <7.5% (58.5 mmol/mol). The cumulative number, the incidence rates, as well as the annualized rates of confirmed (<= 3.9 mmol/L and the lower threshold of <3.0 mmol/L) or severe hypoglycemia at any time of the day or during the night were lower with Gla-300 vs Gla-100; this was not affected by the region (all P>0.1). North American participants treated with Gla-300 gained less weight than North American participants treated with Gla-100 (least squares mean change 0.64 kg vs 1.15 kg), whereas in non-North American participants the change in weight tended to be similar in both treatment groups (0.36 kg vs 0.32 kg). Treatment with Gla-300 and Gla-100 was well tolerated in both regions. Conclusion: Gla-300 provided comparable glycemic control to Gla-100 with consistently less hypoglycemia at any time of day and during the night, regardless of the region (North America/outside North America).