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

AimTo 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 MethodsA 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.ResultsThe 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.ConclusionsGla‐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.

Switching to insulin glargine 300 units/mL in real‐world older patients with type 2 diabetes (DELIVER 3)

“…There was, however, significantly less confirmed/severe hypoglycaemia with Gla‐300 versus Gla‐100 across all age groups. In a recent meta‐analysis of three EDITION RCTs (EDITION 1, 2, and 3), patients with mild‐to‐moderate renal impairment had a similar reduced risk of hypoglycaemia with Gla‐300 versus Gla‐100 to patients without renal impairment . These data may be particularly relevant for older adults who are more likely to have such comorbidities.…”

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

“…There are no RCTs that have specifically assessed the use of second-generation BI in people with T2DM and renal insufficiency. However, the use of these agents in this at-risk population can be gleaned from a meta-analysis of Gla-300 RCTs [ 69 ], some exploratory data from a subgroup analysis of BRIGHT [ 70 ] and predictive modeling data based on RWE from the LIGHTNING study [ 43 ].…”

“…Patients with eGFR < 15 mL/min/1.73 m 2 were not included in this analysis as these patients were excluded from the EDITION studies. The mean baseline eGFR was 48.6 mL/min/1.73 m 2 in the lower eGFR group and 85 mL/min/1.73 m 2 in the higher eGFR group [ 69 ]. Overall, more patients in the lower eGFR subgroup experienced hypoglycemia compared with the higher eGFR subgroup.…”

“…The authors reported a reduced risk of nocturnal confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemia with Gla-300 versus Gla-100 in both renal function subgroups (eGFR < 60 mL/min/1.73 m 2 : RR 0.76, 95% CI 0.62–0.94; eGFR ≥ 60 mL/min/1.73 m 2 : RR 0.75, 95% CI 0.67–0.85). For confirmed (≤ 70 mg/dL [≤ 3.9 mmol/L]) or severe hypoglycemia at any time of day, the hypoglycemia risk was lower with Gla-300 than with 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 cohorts [ 69 ]. The frequency of TEAEs were similar between the Gla-300- and Gla-100-treated patients, although more TEAEs were reported in participants with poorer renal sufficiency (eGFR < 60 mL/min/1.73 m 2 ) versus the group with a higher eGFR (≥ 60 mL/min/1.73 m 2 ).…”

“…The frequency of TEAEs were similar between the Gla-300- and Gla-100-treated patients, although more TEAEs were reported in participants with poorer renal sufficiency (eGFR < 60 mL/min/1.73 m 2 ) versus the group with a higher eGFR (≥ 60 mL/min/1.73 m 2 ). In the lower eGFR subgroup, 64.7 and 59.4% of participants in the Gla-300 and Gla-100 treatment groups, respectively, experienced TEAEs compared with 55.8 and 52.5% of participants in the Gla-300 and Gla-100 treatment groups, respectively, in the higher eGFR subgroup [ 69 ].…”