New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin‐naïve people with type 2 diabetes on oral glucose‐lowering drugs: a randomized controlled trial (EDITION 3)

Abstract

AimsTo compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of glargine 100 U/ml (Gla-100) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs.MethodsThe EDITION 3 study was a multicentre, open-label, parallel-group study. Participants were randomized to Gla-300 or Gla-100 once daily for 6 months, discontinuing sulphonylureas and glinides, with a dose titration aimed at achieving pre-breakfast plasma glucose concentrations of 4.4–5.6 mmol/l (80–100 mg/dl). The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to month 6. The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia from week 9 to month 6. Other measures of glycaemia and hypoglycaemia, weight change and insulin dose were assessed.ResultsRandomized participants (n = 878) had a mean (standard deviation) age of 57.7 (10.1) years, diabetes duration 9.8 (6.4) years, body mass index 33.0 (6.7) kg/m2 and HbA1c 8.54 (1.06) % [69.8 (11.6) mmol/mol]. HbA1c levels decreased by equivalent amounts with the two treatments; the least squares mean difference in change from baseline was 0.04 [95% confidence interval (CI) −0.09 to 0.17] % or 0.4 (−1.0 to 1.9) mmol/mol. Numerically fewer participants reported ≥1 nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia from week 9 to month 6 [relative risk (RR) 0.89 (95% CI 0.66 to 1.20)] with Gla-300 versus Gla-100; a significantly lower risk of hypoglycaemia with this definition was found over the 6-month treatment period [RR 0.76 (95% CI 0.59 to 0.99)]. No between-treatment differences in adverse events were identified.ConclusionsGla-300 is as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes, with lower hypoglycaemia risk.

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

“…This finding was accompanied by a lower risk of nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla‐300 than Gla‐100, which was not influenced by renal function. Hence, overall, the pooled results presented here are consistent with the individual EDITION studies,14, 15, 16 which also reported similar glycaemic control and reduced risk of hypoglycaemia with Gla‐300 compared with Gla‐100. Importantly, however, these data show that this advantage of Gla‐300 over Gla‐100 was maintained in people with T2DM and impaired renal function.…”

“…Insulin glargine 300 U/mL (Gla‐300), a second‐generation basal insulin, provides a more stable and prolonged pharmacokinetic and pharmacodynamic profile compared with insulin glargine 100 U/mL (Gla‐100) 13. Data from the phase III EDITION 1, 2 and 3 clinical trials showed that over 6 months, Gla‐300 provided similar glycaemic control to Gla‐100 in participants with T2DM, with less hypoglycaemia 14, 15, 16. Given the reduced hypoglycaemia risk with Gla‐300 vs Gla‐100, we were interested to see if this benefit persisted in individuals with impaired renal function.…”

Insulin U100, 200, 300 or 500?

“…The risk of any confirmed or severe hypoglycaemia was lower with IGlarU300 over the 6-month treatment period (RR 0.76 [95% CI 0.59 to 0.99]). 27 EDITION JP2, focusing on Japanese subjects, showed a similar decline in HbA1c over 6 months with no differences observed in changes from baseline and fasting plasma glucose or in the percentage of patients reaching the HbA1c target of less than 7%. Hypoglycaemia was lower, particularly in the first 8 weeks of the study.…”

“…Although IGlarU300 tended to require a higher dose, the weight changes were either comparable or favoured IGlarU300. 25,27 Patients in …”

Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus other basal insulins in insulin-naïve patients with type 2 diabetes

“…In pharmacokinetics and pharmacodynamics studies, insulin glargine 300 U/mL (Gla-300) has demonstrated low variability in exposure over 24 h, a more consistent activity profile, and prolonged maintenance of glucose control compared with insulin glargine 100 U/mL (Gla-100) [8][9][10]. In the randomized, controlled Phase III EDITION clinical trial program, Gla-300 was shown to be non-inferior to Gla-100 in reducing HbA1c levels, without increasing the risk of hypoglycemia versus Gla-100 in patients with type 1 diabetes (T1D) or T2D at 6 months [11][12][13][14] and at 1 year [15,16]. The proportion of patients who experienced ≥1 confirmed (blood glucose [BG] ≤70 mg/dL) or severe nocturnal hypoglycemic event was significantly lower for Gla-300 than for Gla-100 [17].…”