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.

OBJECTIVETo compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes on basal insulin ( ‡42 units/day) plus mealtime insulin. RESEARCH DESIGN AND METHODSEDITION 1 (NCT01499082) was a 6-month, multinational, open-label, parallelgroup study. Adults with glycated hemoglobin A 1c (HbA 1c ) 7.0-10.0% (53-86 mmol/mol) were randomized to Gla-300 or Gla-100 once daily with dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L. Primary end point was HbA 1c change from baseline; main secondary end point was percentage of participants with one or more confirmed (£3.9 mmol/L) or severe nocturnal hypoglycemia from week 9 to month 6. RESULTSParticipants (n = 807) had mean age 60 years, diabetes duration 16 years, BMI 36.6 kg/m 2 , and HbA 1c 8.15% (65.6 mmol/mol). HbA 1c reduction was equivalent between regimens; least squares mean difference -0.00% (95% CI -0.11 to 0.11) (-0.00 mmol/mol [-1.2 to 1.2]). Fewer participants reported one or more confirmed (£3.9 mmol/L) or severe nocturnal hypoglycemic events between week 9 and month 6 with Gla-300 (36 vs. 46% with Gla-100; relative risk 0.79 [95% CI 0.67-0.93]; P < 0.005); nocturnal hypoglycemia incidence and event rates were also lower with Gla-300 in the first 8 weeks of treatment. No between-treatment differences in tolerability or safety were identified. CONCLUSIONSGla-300 controls HbA 1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin but with consistently less risk of nocturnal hypoglycemia.

OBJECTIVETo compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes using basal insulin ( ‡42 units/day) plus oral antihyperglycemic drugs (OADs). RESEARCH DESIGN AND METHODSEDITION 2 was a multicenter, open-label, two-arm study. Adults receiving basal insulin plus OADs were randomized to Gla-300 or Gla-100 once daily for 6 months. The primary end point was change in HbA 1c . The main secondary end point was percentage of participants with one or more nocturnal confirmed (£3.9 mmol/L [£70 mg/dL]) or severe hypoglycemic events from week 9 to month 6. RESULTSRandomized participants (n = 811) had a mean (SD) HbA 1c of 8.24% (0.82) and BMI of 34.8 kg/m 2 (6.4). Glycemic control improved similarly with both basal insulins; least squares mean (SD) reduction from baseline was 20.57% (0.09) for Gla-300 and 20.56% (0.09) for Gla-100 (mean difference 20.01% [95% CI 20.14 to 0.12]), with 10% higher dose of Gla-300. Less nocturnal confirmed (£3.9 mmol/L [£70 mg/dL]) or severe hypoglycemia was observed with Gla-300 from week 9 to month 6 (relative risk 0.77 [95% CI 0.61-0.99]; P = 0.038) and during the first 8 weeks. Fewer nocturnal and any time (24 h) hypoglycemic events were reported during the entire 6-month period. Weight gain was lower with Gla-300 than with Gla-100 (P = 0.015). No between-treatment differences in safety parameters were identified. CONCLUSIONSGla-300 was as effective as Gla-100 and associated with a lower risk of hypoglycemia during the night and at any time of the day.

OBJECTIVE -Available basal insulin formulations do not provide a constant and reliable 24-h insulin supply. We compared the efficacy and safety of glargine (a long-acting insulin analog) and NPH insulins in insulin-naive type 2 diabetic patients treated with oral antidiabetic agents.RESEARCH DESIGN AND METHODS -There were 426 type 2 diabetic patients (age 59 ± 9 years, BMI 28.9 ± 4.3 kg/m 2 , mean ± SD) with poor glycemic control on oral antidiabetic agents randomized to treatment for 1 year with bedtime insulin glargine or bedtime NPH insulin. Oral agents were continued unchanged. The fasting blood glucose (FBG) target was 6.7 mmol/l (120 mg/dl). RESULTS -Average glycemic control improved similarly with both insulins (HbA 1c[reference range Ͻ6.5%] 8.3 ± 0.1 vs. 8.2 ± 0.1% at 1 year, glargine vs. NPH, mean ± SEM, P Ͻ 0.001 vs. baseline for both). However, there was less nocturnal hypoglycemia (9.9 vs. 24.0% of all patients, glargine vs. NPH, P Ͻ 0.001) and lower post-dinner glucose concentrations (9.9 ± 0.2 vs. 10.7 ± 0.3 mmol/l, P Ͻ 0.02) with insulin glargine than with NPH. Insulin doses and weight gain were comparable. In patients reaching target FBG, HbA 1c averaged 7.7 and 7.6% in the glargine and NPH groups at 1 year.CONCLUSIONS -Use of insulin glargine compared with NPH is associated with less nocturnal hypoglycemia and lower post-dinner glucose levels. These data are consistent with peakless and longer duration of action of insulin glargine compared with NPH. Achievement of acceptable average glucose control requires titration of the insulin dose to an FBG target Յ6.7 mmol/l. These data support use of insulin glargine instead of NPH in insulin combination regimens in type 2 diabetes.

OBJECTIVEInsulin therapy in type 1 diabetes still provides suboptimal outcomes. Insulin glargine 300 units/mL (Gla-300), with a flatter pharmacodynamic profile compared with insulin glargine 100 units/mL (Gla-100), is an approach to this problem. RESEARCH DESIGN AND METHODSPeople with type 1 diabetes, using a mealtime and basal insulin regimen, were randomized open-label to Gla-300 or Gla-100 and to morning or evening injection, continuing the mealtime analog, and followed for 6 months. RESULTSParticipants (n = 549) were a mean age of 47 years and had a mean duration of diabetes of 21 years and BMI of 27.6 kg/m 2 . The change in HbA 1c (primary end point; baseline 8.1%) was equivalent in the two treatment groups (difference, 0.04% [95% CI 20.10 to 0.19]) (0.4 mmol/mol [21.1 to 2.1]), and Gla-300 was thus noninferior. Similar results with wider 95% CIs were found for morning and evening injection times and for prebreakfast self-measured plasma glucose (SMPG) overall. Results were also similar for Gla-300 when morning and evening injection time was compared, including overlapping 8-point SMPG profiles. Hypoglycemia did not differ, except for the first 8 weeks of the study, when nocturnal confirmed or severe hypoglycemia was lower with Gla-300 (rate ratio 0.69 [95% CI 0.53-0.91]). Hypoglycemia with Gla-300 did not differ by time of injection. The basal insulin dose was somewhat higher at 6 months for Gla-300. The adverse event profile did not differ and was independent of the Gla-300 time of injection. Weight gain was lower with Gla-300. CONCLUSIONSIn long-duration type 1 diabetes, Gla-300 provides similar glucose control to Gla-100, with a lower risk of hypoglycemia after transfer from other insulins, independent of time of injection, and less weight gain.Type 1 diabetes requires life-long insulin therapy, with consequences for quality of life (1). Accordingly, insulin administration should be convenient and support selfmanagement by being adaptable to individual lifestyle. Current recommendations are generally basal plus mealtime insulin injections with insulin analogs, or pump