Association of Patient Profile with Glycemic Control and Hypoglycemia with Insulin Glargine 300 U/mL in Type 2 Diabetes: A Post Hoc Patient-Level Meta-Analysis

Abstract

AimsTo examine the association of baseline patient characteristics with study outcomes in people with type 2 diabetes receiving insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100), over a 6-month period.MethodsA post hoc patient-level meta-analysis using data from three multicenter, randomized, open-label, parallel-group, phase 3a studies of similar design, in people previously receiving either basal and prandial insulin, basal insulin + oral antihyperglycemic drugs, or no prior insulin (EDITION 1, 2 and 3, respectively). The endpoints, glycated hemoglobin (HbA1c), hypoglycemia, body weight change, and insulin dose were investigated by subgroups: age (< 65 and ≥ 65 years), body mass index (BMI; < 30 and ≥ 30 kg/m2), age at onset (< 40, 40–50, and > 50 years), and diabetes duration (< 10 and ≥ 10 years).ResultsReduction in HbA1c was comparable between insulins, regardless of subgroup. The lower risk of ≥ 1 nocturnal (00:00–05:59 h) confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemic event with Gla-300 versus Gla-100 was also unaffected by participant characteristics. While heterogeneity of treatment effect between diabetes duration subgroups was seen for the risk of ≥ 1 confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemic event at any time (24 h), treatment effect consistently favored Gla-300; no evidence of heterogeneity was observed for the other subgroups. Annualized rates of confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemia and body weight change were not influenced by participant characteristics; a similar pattern was observed with insulin dose.ConclusionsComparable glycemic control was observed with Gla-300 versus Gla-100, with less hypoglycemia, regardless of age, BMI, age at onset or diabetes duration.FundingSanofi.Plain Language SummaryPlain language summary available for this article.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-018-0498-x) contains supplementary material, which is available to authorized users.

The Safety and Efficacy of Second-Generation Basal Insulin Analogues in Adults with Type 2 Diabetes at Risk of Hypoglycemia and Use in Other Special Populations: A Narrative Review

“…A number of meta-analyses of phase IIIa trials have evaluated Gla-300 or IDeg versus Gla-100. Consistent with the outcomes reported in the phase IIIa RCTs, these meta-analyses support less hypoglycemia with second-generation versus first-generation BI analogues (Appendix 2 ) [ 20 – 22 , 27 , 29 , 31 , 32 , 35 , 36 , 38 , 40 , 41 ].…”

“…Most patients in the EDITION and BEGIN pivotal clinical trials had obesity. The mean BMI of patients in the EDITION studies was 34.8 (range 32.8-36.6) kg/m 2 [35] and that of the T2DM patients in the BEGIN studies was 30.14 kg/m 2 [29].…”

“…Several meta-analyses of the EDITION and BEGIN studies have assessed the effectiveness and safety of second-generation BI analogues for the treatment of T2DM in older versus younger subjects [35,[62][63][64]. A patient-level meta-analysis of EDITION 1, 2 and 3 revealed [64].…”

“…Several meta-analyses of the EDITION and BEGIN studies have assessed the effectiveness and safety of second-generation BI analogues for the treatment of T2DM in older versus younger subjects [ 35 , 62 – 64 ]. A patient-level meta-analysis of EDITION 1, 2 and 3 revealed that there was a comparable reduction in HbA1c and a lower risk of nocturnal hypoglycemia with Gla-300 versus Gla-100, which was more apparent in the subgroup of subjects aged ≥ 65 years (mean age 69.6 years) than in that aged < 65 years (mean age 54.7 years) (relative risk 0.77, 95% CI 0.68–0.87 vs. 0.70, 95% CI 0.57–0.85, respectively) [ 64 ].…”

“…Published studies have shown that second-generation BIs are as effective as Gla-100 at controlling HbA1c, with a similar or lower risk of hypoglycemia in a broad range of patients, including high-risk patients with a long duration of diabetes (> 10 years) and those with a long duration on insulin treatment (> 5 years) [ 11 , 23 , 30 , 35 , 65 , 69 ].…”