Better glycaemic control and less hypoglycaemia with insulin glargine 300 U/mL vs glargine 100 U/mL: 1-year patient-level meta-analysis of the EDITION clinical studies in people with type 2 diabetes

Abstract

Aims: To investigate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) vs insulin glargine 100 U/mL (Gla-100) over 12 months in a patient-level meta-analysis, using data from the EDITION studies in people with type 2 diabetes (T2DM).

Methods: EDITION 1, 2 and 3 were multicentre, randomized, open-label, 2-arm, parallel-group, treat-to-target phase IIIa studies. Similar study designs and endpoints enabled a meta-analysis to be conducted.

Results: Reductions in glycated haemoglobin (HbA1c) were better sustained over 12 months with Gla-300 than with Gla-100 (least squares [LS] mean difference in change from baseline: -0.10 % [95% confidence interval {CI} -0.18 to -0.02] or -1.09 mmol/mol [95% CI -2.01 to -0.20]; P = .0174). Risk of confirmed (≤3.9 mmol/L) or severe hypoglycaemia was 15% lower with Gla-300 vs Gla-100 at night (relative risk 0.85 [95% CI 0.77-0.92]) and 6% lower at any time of day (relative risk 0.94 [95% CI 0.90-0.98]). Rates of hypoglycaemia were 18% lower with Gla-300 vs Gla-100 at night (rate ratio 0.82 [95% CI 0.67-0.99]), but comparable at any time of day. HbA1c <7.0 % without nocturnal hypoglycaemia was achieved by 24% more participants with Gla-300 than with Gla-100 (relative risk 1.24 [95% CI 1.03-1.50]). Severe hypoglycaemia was rare; in both treatment groups the incidence of events at any time of day was ≤3.6%, while rates were ≤0.08 events per participant-year.

Conclusions: In a broad population of people with T2DM over 12 months, use of Gla-300 provided more sustained glycaemic control and significantly lower hypoglycaemia risk at night and at any time of day compared with Gla-100.

Keywords: glycaemic control; hypoglycaemia; insulin analogues; meta-analysis; phase III study; type 2 diabetes.

Figure 1

HbA1c (mean ± s.e.) over the 12‐month treatment period (mITT population). LS mean difference analysed using a mixed model for repeated measures. BL, baseline; M, month; W, week

Figure 2

Percentage of participants with ≥1 hypoglycaemic event and annualized event rate (events per participant‐year) over the 12‐month treatment period (safety population). RR, relative risk for percentage of participants with ≥1 event, rate ratio for annualized event rates

Figure 3

Confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia by time of day over the 12‐month treatment period. A, Percentage of participants with ≥1 event and B, annualized event rates (events per participant‐year; safety population)

Figure 4

Percentage of participants achieving HbA1c targets (HbA1c <7.0 % or <7.5 % or HbA1c reduction ≥0.5 %) at month 12 without confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia over 12 months of treatment (mITT population). RR, relative risk

Figure 5

A, Mean (± s.e.) daily basal insulin dose over 12 months of treatment (mITT population) and B, mean (± s.e.) change in body weight from baseline to month 12 (safety population). BL, baseline; M, month; W, week