Glycaemic control and hypoglycaemia benefits with insulin glargine 300 U/mL extend to people with type 2 diabetes and mild-to-moderate renal impairment

Abstract

Aim: To investigate the impact of renal function on the safety and efficacy of insulin glargine 300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100).

Materials and methods: A meta-analysis was performed using pooled 6-month data from the EDITION 1, 2 and 3 trials (N = 2496). Eligible participants, aged ≥18 years with a diagnosis of type 2 diabetes (T2DM), were randomized to receive once-daily evening injections of Gla-300 or Gla-100. Pooled results were assessed by two renal function subgroups: estimated glomerular filtration rate (eGFR) <60 and ≥60 mL/min/1.73 m² .

Results: The decrease in glycated haemoglobin (HbA1c) after 6 months and the proportion of individuals with T2DM achieving HbA1c targets were similar in the Gla-300 and Gla-100 groups, for both renal function subgroups. There was a reduced risk of nocturnal (12:00-5:59 am) confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 in both renal function subgroups (eGFR <60 mL/min/1.73 m² : relative risk [RR] 0.76 [95% confidence interval {CI} 0.62-0.94] and eGFR ≥60 mL/min/1.73 m² : RR 0.75 [95% CI 0.67-0.85]). For confirmed (≤70 mg/dL [≤3.9 mmol/L]) or severe hypoglycaemia at any time of day (24 hours) the hypoglycaemia risk was lower with Gla-300 vs Gla-100 in both the lower (RR 0.94 [95% CI 0.86-1.03]) and higher (RR 0.90 [95% CI 0.85-0.95]) eGFR subgroups.

Conclusions: Gla-300 provided similar glycaemic control to Gla-100, while indicating a reduced overall risk of confirmed (≤3.9 and <3.0 mmol/L [≤70 and <54 mg/dL]) or severe hypoglycaemia, with no significant difference between renal function subgroups.

Keywords: basal insulin; glycaemic control; hypoglycaemia; insulin analogues; meta-analysis; type 2 diabetes.

Figure 1

A, Mean change in glycated haemoglobin (HbA1c) from baseline to month 6 according to renal function subgroup (modified intention‐to‐treat [mITT] population). †Logistic method; P < 0.05 corresponds to significant heterogeneity of treatment effect. B, Percentage of participants achieving HbA1c targets (53 mmol/mol [<7.0%] and 58.5 mmol/mol [<7.5%]) at month 6 (mITT population). CI, confidence interval; eGFR, estimated glomerular filtration rate; Gla‐100, insulin glargine 100 U/mL; Gla‐300, insulin glargine 300 U/mL; LS, least squares; MMRM, mixed model for repeated measurements

Figure 2

A, Percentage of participants experiencing ≥1 confirmed or severe hypoglycaemic event (safety population). B, Relative risk of experiencing ≥1 hypoglycaemic event with insulin glargine 300 U/mL (Gla‐300) vs insulin glargine 100 U/mL (Gla‐100) by renal function subgroup (safety population). †Logistic method. P < 0.05 corresponds to significant heterogeneity of treatment effect. CI, confidence interval; eGFR, estimated glomerular filtration rate

Figure 3

A, Rate of confirmed or severe hypoglycaemia by renal function subgroup (safety population). B, Ratio of annualized hypoglycaemia event rates by renal function subgroup (safety population). †Logistic method. P < 0.05 corresponds to significant heterogeneity of treatment effect. CI, confidence interval; eGFR, estimated glomerular filtration rate