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Background: We compared the efficacy and safety of insulin glulisine with insulin lispro as part of a basal-bolus regimen in children and adolescents with type 1 diabetes., Methods: Overall, 572 children and adolescents (4-17 years old) using insulin glargine or neutral protamine Hagedorn insulin as basal insulin were enrolled in a 26-week, multicenter, open, centrally randomized, parallel-group, noninferiority study. Subjects were randomized to receive glulisine (n = 277) or lispro (n= 295) 0-15 min premeal., Results: Baseline-to-endpoint hemoglobin A1c changes were similar between the two insulins: adjusted mean change (glulisine vs. lispro), 0.10% versus 0.16%; between-treatment difference (glulisine-lispro), &minsu;0.06, 95% confidence interval (-0.24; 0.12); and prespecified noninferiority margin, 0.4%. Overall, for all age groups together, the percentage of patients achieving American Diabetes Association age-specific A1c targets at endpoint was significantly higher (P = 0.039) with glulisine (38.4%) versus lispro (32.0%). From Month 4 to endpoint, both "all" and "severe" symptomatic hypoglycemia rates were similar (3.10 vs. 2.91 and 0.06 vs. 0.07 events/patient-month, respectively). Frequency and type of adverse events, serious adverse events, or hypoglycemia reported as serious adverse events were similar between both groups., Conclusions: Glulisine was as effective as lispro in baseline-to-endpoint A1c change, and both treatments were similarly well tolerated.

Aims: To explore details of the incidence and rates of daytime and nocturnal hypoglycaemia, levels of hypoglycaemia, and relationship to glycated haemoglobin (HbA1c), when comparing iGlarLixi versus premixed biphasic insulin aspart 30 (BIAsp 30) in the SoliMix randomized controlled trial. Materials and Methods: This exploratory analysis of SoliMix used logistic regression and negative binomial regression analyses to assess between‐treatment differences in the incidence and rates of hypoglycaemia by time of day. A negative binomial model was used to derive estimated annualized hypoglycaemia rates as a function of HbA1c. Results: iGlarLixi was associated with lower incidence and rates of American Diabetes Association Level 2 (<54 mg/dL [<3.0 mmol/L]) hypoglycaemia during both night and day versus BIAsp 30. Incidence and rates of Level 1 (<70 to ≥54 mg/dL [<3.9 to ≥3.0 mmol/L]) hypoglycaemia were also mostly shown to be reduced with iGlarLixi versus BIAsp 30. Severe (Level 3) events were too few for analysis (n = 3). iGlarLixi was associated with lower modelled event rates of Level 2 and Level 1 hypoglycaemia over a wide range of HbA1c levels versus BIAsp 30. Conclusions: These results show that the lower HbA1c levels and weight benefit seen with iGlarLixi versus premixed BIAsp 30 in people with type 2 diabetes advancing their basal insulin therapy in the SoliMix trial are also accompanied by a lower risk of hypoglycaemia at any time of day and across a broad range of HbA1c levels. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the efficacy and safety of iGlarLixi compared with iGlar in Chinese adults with type 2 diabetes advancing therapy from basal insulin ± oral antihyperglycaemic drugs. Materials and methods: LixiLan‐L‐CN (NCT03798080) was a 30‐week randomized, active‐controlled, open‐label, parallel‐group, multicentre study. Participants were randomized 1:1 to iGlarLixi or iGlar. The primary objective was to show the superiority of iGlarLixi over iGlar in glycated haemoglobin (HbA1c) change from baseline to Week 30. Results: In total, 426 participants were randomized to iGlarLixi (n = 212) or iGlar (n = 214). Mean age was 58 years, 67% had a body mass index ≥24 kg/m2, corresponding to overweight/obesity, and the mean diabetes duration was 12.3 years. From mean baseline HbA1c of 8.1% in both groups, greater decreases were seen with iGlarLixi versus iGlar [least squares mean difference: −0.7 (95% confidence interval: −0.9, −0.6)%; p <.0001] to final HbA1c of 6.7% and 7.4%, respectively. HbA1c <7.0% achievement was greater with iGlarLixi (63.3%) versus iGlar (29.9%; p <.0001). Mean body weight decreased with iGlarLixi and increased with iGlar [least squares mean difference: −0.9 (95% confidence interval: −1.4, −0.5) kg; p =.0001]. Hypoglycaemia incidence was similar between groups. Few gastrointestinal adverse events occurred (rated mild/moderate) with a slightly higher incidence with iGlarLixi than iGlar. Conclusions: iGlarLixi provided better glycaemic control and facilitated more participants to reach glycaemic targets alongside beneficial effects on body weight, no additional risk of hypoglycaemia, and few gastrointestinal AEs, supporting iGlarLixi use as an efficacious and well tolerated therapy option in Chinese people with long‐standing T2D advancing therapy from basal insulin. [ABSTRACT FROM AUTHOR]

Aims: To compare the efficacy and safety of iGlarLixi with insulin glargine 100 units/mL (iGlar) and lixisenatide (Lixi), in Asian Pacific people with suboptimally controlled type 2 diabetes (T2D) on metformin with or without a second oral antihyperglycaemic drug (OAD). Materials and Methods: LixiLan‐O‐AP (NCT03798054) was a 24‐week multicentre study in adults (n = 878, mean age 56.0 years, mean body mass index 26.0 kg/m2) with glycated haemoglobin (HbA1c) levels ≥53 mmol/mol (7%) and ≤97 mmol/mol (11%) on OAD(s), randomized (2:2:1) to open‐label once‐daily iGlarLixi, iGlar or Lixi while on continued metformin ± sodium‐glucose cotransporter‐2 inhibitors. The primary efficacy endpoint was change in HbA1c. Results: After 24 weeks, greater reductions in HbA1c from baseline (67 mmol/mol; 8.3%) were seen with iGlarLixi (−21 mmol/mol; −1.9%) compared with iGlar (−16 mmol/mol; −1.4%; P < 0.0001) and Lixi (−10 mmol/mol; −0.9%; P < 0.0001). Greater proportions of participants achieved HbA1c <53 mmol/mol (<7%) with iGlarLixi versus iGlar or Lixi (79%, 60% and 30%, respectively), overall and as composite endpoints including weight and hypoglycaemia. iGlarLixi improved 2‐hour postprandial glucose versus iGlar and Lixi and mitigated the weight gain seen with iGlar (least squares mean difference −1.1 kg; P < 0.0001). Documented ≤3.9 mmol/L (≤70 mg/dL) hypoglycaemia was similar between iGlarLixi and iGlar (both 3.38 events per participant‐year). The incidence rates of nausea and vomiting were lower with iGlarLixi (14% and 6%) than Lixi (21% and 11%). Conclusions: iGlarLixi achieved significant HbA1c reductions, to near‐normoglycaemic levels, compared with iGlar or Lixi, with no meaningful additional risk of hypoglycaemia and mitigated body weight gain versus iGlar, with fewer gastrointestinal adverse events versus Lixi. iGlarLixi with specifically adapted ratios may provide an efficacious and well‐tolerated treatment option for Asian Pacific people with T2D. [ABSTRACT FROM AUTHOR]

Objective: The LixiLan clinical trials of insulin glargine (iGlar)/lixisenatide fixed-ratio combination (iGlarLixi) investigated the safety and efficacy of iGlarLixi versus iGlar: LixiLan-O (NCT02058147) in patients with type 2 diabetes (T2D) inadequately controlled on oral antidiabetes drugs (OADs) and LixiLan-L (NCT02058160) in patients with T2D inadequately controlled on basal insulin ± OADs. In these two trials, both iGlar and iGlarLixi were titrated to a maximum (capped) dose of 60 units. We evaluated whether this may have affected the reported glycemic efficacy of iGlar, and the glycemic differences observed between treatment with iGlarLixi and iGlar.Methods: The efficacy of iGlar under uncapped conditions was simulated in a two-step approach. First, a model characterizing the relationship between iGlar dose and fasting self-measured plasma glucose (f-SMPG) was developed. Then, the relationship between glycated hemoglobin A1c (A1C) and f-SMPG was established to translate simulated f-SMPG responses to A1C responses.Results: Most patients achieved stable f-SMPG at ∼60 units/day, with no further reduction with increasing insulin dose. In comparisons of observed/capped and simulated/uncapped changes in mean A1C from baseline to Week 30, iGlarLixi consistently demonstrated treatment benefit compared with iGlar. Uncapping resulted in a slightly higher mean iGlar dose in both LixiLan-O (+0.72 units) and LixiLan-L (+2.1 units), without marked impact on f-SMPG or A1C change from baseline.Conclusion: Uncapping the iGlar dose in LixiLan-O and LixiLan-L would not have led to significant improvements in mean A1C reduction in the iGlar arm, supporting the conclusion that iGlarLixi provides additional, clinically relevant glycemic control versus iGlar alone. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to demonstrate the efficacy and safety of LixiLan (iGlarLixi), a novel, titratable, fixed-ratio combination of insulin glargine (iGlar) (100 units) and lixisenatide, compared with iGlar in patients with type 2 diabetes inadequately controlled on basal insulin with or without up to two oral glucose-lowering agents.Research Design and Methods: After a 6-week run-in when iGlar was introduced and/or further titrated, and oral antidiabetic drugs other than metformin were stopped, 736 basal insulin-treated patients (mean diabetes duration 12 years, BMI 31 kg/m2) were randomized 1:1 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 dose of 60 units/day. The primary outcome was change in HbA1c levels at 30 weeks.Results: HbA1c decreased from 8.5% (69 mmol/mol) to 8.1% (65 mmol/mol) during the run-in period. After randomization, iGlarLixi showed greater reductions in HbA1c from baseline compared with iGlar (-1.1% vs. -0.6%, P < 0.0001), reaching a mean final HbA1c of 6.9% (52 mmol/mol) compared with 7.5% (58 mmol/mol) for iGlar. HbA1c <7.0% (53 mmol/mol) was achieved in 55% of iGlarLixi patients compared with 30% on iGlar. Mean body weight decreased by 0.7 kg with iGlarLixi and increased by 0.7 kg with iGlar (1.4 kg difference, P < 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was comparable between groups. Mild gastrointestinal adverse effects were very low but more frequent with iGlarLixi.Conclusions: Compared with iGlar, a substantially higher proportion of iGlarLixi-treated patients achieved glycemic targets with a beneficial effect on body weight, no additional risk of hypoglycemia, and low levels of gastrointestinal adverse effects in inadequately controlled, basal insulin-treated, long-standing type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To 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 Methods: After 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/m2) 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 μg/day) while continuing with metformin. The primary outcome was HbA1c change at 30 weeks.Results: Greater reductions in HbA1c from baseline (8.1% [65 mmol/mol]) were achieved with iGlarLixi compared with iGlar and Lixi (-1.6%, -1.3%, -0.9%, respectively), reaching mean final HbA1c 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 HbA1c <7% with iGlarLixi (74%) versus iGlar (59%) or Lixi (33%) (P < 0.0001 for all). Mean body weight decreased with iGlarLixi (-0.3 kg) and Lixi (-2.3 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).Conclusions: iGlarLixi complemented iGlar and Lixi effects to achieve meaningful HbA1c reductions, close to near normoglycemia without increases in either hypoglycemia or weight, compared with iGlar, and had low gastrointestinal adverse effects compared with Lixi. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the efficacy and safety of LixiLan, a fixed-ratio, titratable, combination of 2 units insulin glargine (Gla-100) and 1 μg lixisenatide administered once daily via a single pen, versus Gla-100 in insulin-naïve type 2 diabetes on metformin.Research Design and Methods: Participants were randomized to once-daily LixiLan (n = 161) or Gla-100 (n = 162) for 24 weeks, while continuing metformin. LixiLan and Gla-100 were started at 10 units/5 μg and 10 units, respectively, and titrated based on the Gla-100 requirement according to fasting plasma glucose levels. The primary objective was to test noninferiority (upper bound of the 95% CI ≤0.4%) of LixiLan in reducing HbA1c; if met, statistical superiority was tested. Secondary objectives included body weight changes, hypoglycemia, and safety.Results: Baseline characteristics (mean age 57 years, diabetes duration 6-7 years, BMI 32 kg/m(2)) were similar between groups. At week 24, mean HbA1c was reduced from 8.0% (64 mmol/mol) at baseline to 6.3% (45 mmol/mol) and 6.5% (48 mmol/mol) with LixiLan and Gla-100, respectively, establishing statistical noninferiority and superiority of LixiLan (least-squared mean [95% CI] difference: -0.17% [-0.31, -0.04] {-1.9 mmol/mol [-3.4, -0.4]}; P = 0.01). HbA1c <7.0% (<53 mmol/mol) was achieved in 84% and 78% of participants (nonsignificant), respectively. LixiLan improved 2-h postmeal plasma glucose versus Gla-100 (least-squared mean difference: -3.17 mmol/L [-57 mg/dL]; P < 0.0001). Body weight was reduced with LixiLan (-1 kg) and increased with Gla-100 (+0.5 kg; P < 0.0001), with no increase in hypoglycemic events (∼25% in each group). The incidence of nausea (7.5%) and vomiting (2.5%) was low with LixiLan.Conclusions: LixiLan achieved statistically significant reductions to near-normal HbA1c levels with weight loss and no increased hypoglycemic risk, compared with insulin glargine alone, and a low incidence of gastrointestinal adverse events in type 2 diabetes inadequately controlled on metformin. [ABSTRACT FROM AUTHOR]

A correction to a previous article "Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The LixiLan-O Randomized Trial" is presented.