OBJECTIVETo evaluate efficacy and safety of LixiLan (iGlarLixi), a novel titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide (Lixi), compared with both components, iGlar and Lixi, given separately in type 2 diabetes inadequately controlled on metformin with or without a second oral glucose-lowering drug. RESEARCH DESIGN AND METHODSAfter a 4-week run-in to optimize metformin and stop other oral antidiabetic drugs, participants (N = 1,170, mean diabetes duration ∼8.8 years, BMI ∼31.7 kg/m 2 ) were randomly assigned to open-label once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose <100 mg/dL (<5.6 mmol/L) up to a maximum insulin dose of 60 units/day, or to once-daily Lixi (20 mg/day) while continuing with metformin. The primary outcome was HbA 1c change at 30 weeks. RESULTSGreater reductions in HbA 1c from baseline (8.1% [65 mmol/mol]) were achieved with iGlarLixi compared with iGlar and Lixi (21.6%, 21.3%, 20.9%, respectively), reaching mean final HbA 1c levels of 6.5% (48 mmol/mol) for iGlarLixi versus 6.8% (51 mmol/mol) and 7.3% (56 mmol/mol) for iGlar and Lixi, respectively (both P < 0.0001). More subjects reached target HbA 1c <7% with iGlarLixi (74%) versus iGlar (59%) or Lixi (33%) (P < 0.0001 for all). Mean body weight decreased with iGlarLixi (20.3 kg) and Lixi (22.3 kg) and increased with iGlar (+1.1 kg, difference 1.4 kg, P < 0.0001). Documented symptomatic hypoglycemia (£70 mg/dL) was similar with iGlarLixi and iGlar (1.4 and 1.2 events/patient-year) and lower with Lixi (0.3 events/ patient-year). iGlarLixi improved postprandial glycemic control versus iGlar and demonstrated considerably fewer nausea (9.6%) and vomiting (3.2%) events than Lixi (24% and 6.4%, respectively). CONCLUSIONSiGlarLixi complemented iGlar and Lixi effects to achieve meaningful HbA 1c reductions, close to near normoglycemia without increases in either hypoglycemia or weight, compared with iGlar, and had low gastrointestinal adverse effects compared with Lixi.

AimsTo compare the efficacy and safety of insulin glargine 300 U/ml (Gla‐300) with glargine 100 U/ml (Gla‐100) in Japanese people with type 2 diabetes using basal insulin plus oral antihyperglycaemic drug(s) [OAD(s)].MethodsThe EDITION JP 2 study (NCT01689142) was a 6‐month, multicentre, open‐label, phase III study. Participants (n = 241, male 61%, mean diabetes duration 14 years, mean weight 67 kg, mean body mass index 25 kg/m2, mean glycated haemoglobin (HbA1c) 8.02 %, mean basal insulin dose 0.24 U/kg/day) were randomized to Gla‐300 or Gla‐100, while continuing OAD(s). Basal insulin was titrated to target fasting self‐monitored plasma glucose 4.4−5.6 mmol/l. The primary efficacy endpoint was HbA1c change over 6 months. Safety endpoints included hypoglycaemia and weight change.ResultsGla‐300 was non‐inferior to Gla‐100 for HbA1c reduction [least squares (LS) mean difference 0.10 (95% confidence interval [CI] −0.08, 0.27) %]. The mean HbA1c at month 6 was 7.56 and 7.52 % with Gla‐300 and Gla‐100, respectively. Nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia risk was 38% lower with Gla‐300 versus Gla‐100 [relative risk 0.62 (95% CI 0.44, 0.88)]; annualized rates were 55% lower at night [rate ratio 0.45 (95% CI 0.21, 0.96)] and 36% lower at any time [24 h; rate ratio 0.64 (95% CI 0.43, 0.96)]. Severe hypoglycaemia was infrequent. A significant between‐treatment difference in weight change favoured Gla‐300 [LS mean difference −1.0 (95% CI −1.5, −0.5) kg; p = 0.0003]. Adverse event rates were comparable between groups.ConclusionsJapanese people with type 2 diabetes using basal insulin plus OAD(s) experienced less hypoglycaemia with Gla‐300 than with Gla‐100, while glycaemic control did not differ.

AimTo compare efficacy and safety of new insulin glargine 300 U/ml (Gla‐300) with that of insulin glargine 100 U/ml (Gla‐100) in Japanese adults with type 1 diabetes.MethodsThe EDITION JP 1 study (NCT01689129) was a 6‐month, multicentre, open‐label, phase III study. Participants (n = 243) were randomized to Gla‐300 or Gla‐100 while continuing mealtime insulin. Basal insulin was titrated with the aim of achieving a fasting self‐monitored plasma glucose target of 4.4–7.2 mmol/l. The primary endpoint was change in glycated haemoglobin (HbA1c) over 6 months. Safety measures included hypoglycaemia and change in body weight.ResultsGla‐300 was non‐inferior to Gla‐100 for the primary endpoint of HbA1c change over the 6‐month period {least squares [LS] mean difference 0.13 % [95 % confidence interval (CI) −0.03 to 0.29]}. The annualized rate of confirmed (≤3.9 mmol/l) or severe hypoglycaemic events was 34 % lower with Gla‐300 than with Gla‐100 at night [rate ratio 0.66 (95 % CI 0.48–0.92)] and 20 % lower at any time of day [24 h; rate ratio 0.80 (95 % CI 0.65–0.98)]; this difference was most pronounced during the first 8 weeks of treatment. Severe hypoglycaemia was infrequent. The basal insulin dose increased in both groups (month 6 dose: Gla‐300 0.35 U/kg/day, Gla‐100 0.29 U/kg/day). A between‐treatment difference in body weight change over 6 months favouring Gla‐300 was observed [LS mean difference −0.6 kg (95 % CI −1.1 to −0.0); p = 0.035]. Adverse event rates were comparable between the groups.ConclusionsIn Japanese adults with type 1 diabetes using basal plus mealtime insulin, less hypoglycaemia was observed with Gla‐300 than with Gla‐100, particularly during the night, while glycaemic control did not differ.

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