Dataset Information

Post hoc efficacy and safety analysis of insulin glargine/lixisenatide fixed- ratio combination in North American patients compared with the rest of world.

ABSTRACT: Objective:To assess the efficacy and safety of iGlarLixi (titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide) in patients with type 2 diabetes (T2D) living in North America (NA; USA and Canada) compared with the rest of the world (RoW). Research design and methods:Post hoc analysis included patient-level data from 509 sites/centers across two phase III trials: LixiLan-O (NCT02058147; insulin-naive patients; NA, n=371; RoW, n=796) and LixiLan-L (NCT02058160; inadequately controlled patients on basal insulin; NA, n=196; RoW, n=535). Efficacy outcomes were: change from baseline to Week 30 in glycated hemoglobin (HbA1c), postprandial glucose (PPG), PPG excursions, fasting plasma glucose (FPG) and body weight; proportion of patients achieving HbA1c <42 mmol/mol (<7.0%); proportion of patients achieving composite endpoint: HbA1c <42 mmol/mol (<7.0%), no weight gain or symptomatic hypoglycemia (blood glucose ?3.9 mmol/L (?70 mg/dL)). Safety endpoints included incidence of documented symptomatic hypoglycemia and gastrointestinal (GI) adverse events. Results:Significantly larger reductions (p?0.003) in HbA1c from baseline to Week 30 were achieved with iGlarLixi, compared with iGlar or lixisenatide, in NA and RoW patients in LixiLan-O (iGlarLixi vs iGlar: -0.31 and -0.29, respectively; iGlarLixi vs lixisenatide: -0.84 and -0.69, respectively) and in LixiLan-L (iGlarLixi vs iGlar: -0.5 and -0.51, respectively). Documented symptomatic hypoglycemia was similar between NA and RoW patients. iGlarLixi resulted in significant weight benefits versus iGlar (change from baseline -1.58 and -1.29 kg for NA and RoW patients, respectively; p<0.001). GI adverse events were similar for iGlarLixi and iGlar, but significantly higher for lixisenatide. Conclusions:iGlarLixi improved glycemic parameters versus iGlar or lixisenatide alone in both NA and RoW patients, with beneficial weight effects versus iGlar. iGlarLixi treatment responses, hypoglycemia risk and GI adverse events in NA patients were comparable with patients in the RoW. Trial registry:Clinicaltrials.gov NCT02058147 and NCT02058160.

SUBMITTER: Dailey G

PROVIDER: S-EPMC6501856 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Post hoc efficacy and safety analysis of insulin glargine/lixisenatide fixed- ratio combination in North American patients compared with the rest of world.

Dailey George G Bajaj Harpreet S HS Dex Terry T Groleau Melanie M Stager William W Vinik Aaron A

BMJ open diabetes research & care 20190321 1

<h4>Objective</h4>To assess the efficacy and safety of iGlarLixi (titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide) in patients with type 2 diabetes (T2D) living in North America (NA; USA and Canada) compared with the rest of the world (RoW).<h4>Research design and methods</h4>Post hoc analysis included patient-level data from 509 sites/centers across two phase III trials: LixiLan-O (NCT02058147; insulin-naive patients; NA, n=371; RoW, n=796) and LixiLan-L (NCT0205 ...[more]

PMID: 31114694

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Project description:IntroductioniGlarLixi is a titratable, fixed-ratio combination of insulin glargine (iGlar, 100 units/ml) and the glucagon-like peptide-1 receptor agonist lixisenatide for the treatment of patients with type 2 diabetes. This post hoc analysis of the phase 3 LixiLan-L trial (NCT02058160) investigated baseline characteristics, glycemic control, and safety outcomes in participants who received the study-specified maximum dose (60 units/day) of iGlarLixi or iGlar vs. those who received < 60 units/day.MethodsOutcomes were compared for participants receiving 60 or < 60 units/day at week 30. Endpoints analyzed included change in A1C, fasting plasma glucose (FPG), 2-h postprandial glucose (2-h PPG), body weight, proportion of participants achieving A1C < 7.0%, proportion of participants receiving rescue therapy, documented symptomatic hypoglycemia, and gastrointestinal adverse event (GI AE) incidence.ResultsBy week 30, 27% (iGlarLixi) and 31% (iGlar) of participants received the maximum dose. Participants on 60 vs. < 60 units/day were younger and had higher body weight, body mass index (BMI), FPG, and baseline insulin dose. In both dose groups, A1C change from baseline was significantly greater with iGlarLixi vs. iGlar, and more participants treated with iGlarLixi vs. iGlar achieved A1C < 7.0%. No significant differences were observed in change from baseline for A1C, FPG, 2-h PPG, or GI AE incidence between insulin dose groups, regardless of treatment. In both treatment arms, incidence of symptomatic hypoglycemia was lower in participants receiving 60 units/day vs. those receiving < 60 units/day. Participants treated with iGlarLixi (< 60 or 60 units/day) had modest weight loss over 30 weeks vs. an increase in weight compared with iGlar.ConclusionsMaximum doses of iGlarLixi were required in participants with a more insulin-resistant clinical phenotype (younger, higher BMI, FPG, and insulin doses). Benefits were observed with iGlarLixi vs. iGlar, even at 60 units/day, with more participants achieving glycemic goals, no increase in symptomatic hypoglycemia, and a modest reduction in body weight.FundingSanofi US, Inc.

Project description:ObjectivesTo assess the effectiveness and safety of insulin glargine and lixisenatide (iGlarLixi) fixed-ratio combination on a cohort of Romanian adults with type 2 diabetes (T2D).DesignOpen-label, 24-week, prospective cohort study.Setting65 secondary care diabetes centres in Romania.ParticipantsThe study included 901 adults with T2D suboptimally controlled with previous oral antidiabetic drugs (OADs)±basal insulin (BI) who initiated treatment with iGlarLixi upon the decision of the investigator. Major exclusion criteria were iGlarLixi contraindications and refusal to participate. 876 subjects received at least one dose of iGlarLixi (intention-to-treat/safety population).Primary and secondary outcome measuresThe primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to week 24 in the modified intention-to-treat population (study participants with HbA1c available at baseline and week 24). Secondary efficacy outcomes were percentage of participants reaching HbA1c targets and change in fasting plasma glucose (FPG).ResultsMean baseline HbA1c was 9.2% (SD 1.4) and FPG was 10.8 mmol/L (2.9). Mean HbA1c change was -1.3% (95% CI: -1.4% to -1.2%, p<0.0001) at week 24. HbA1c levels ≤6.5%, <7% and<7.5% at week 24 were achieved by 72 (8.9%), 183 (22.6%) and 342 (42.3%) participants, respectively. Mean FPG change was -3.1 mmol/L (95% CI: -3.3 to -2.8, p<0.001) at week 24. Mean body weight change was -1.6 kg (95% CI: -1.9 to -1.3, p<0.001) at 24 weeks. Mean iGlarLixi dose increased from 19.5 U (SD 7.7) and 30.1 U (10.0) to 30.2 U (8.9) (ratio 2/1 pen) and 45.0 U (11.6) (ratio 3/1 pen). Adverse events (AEs) were reported by 43 (4.9%) participants (18 (2.1%) gastrointestinal) with 4 (0.5%) reporting serious AEs. 13 (1.5%) participants reported at least one event of symptomatic hypoglycaemia, with one episode of severe hypoglycaemia reported.ConclusionsIn a real-world setting, 24-week treatment with iGlarLixi provided a significant reduction of HbA1c with body weight loss and low hypoglycaemia risk in T2D suboptimally controlled with OADs±BI treatment.

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Post hoc efficacy and safety analysis of insulin glargine/lixisenatide fixed- ratio combination in North American patients compared with the rest of world.

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Post hoc efficacy and safety analysis of insulin glargine/lixisenatide fixed- ratio combination in North American patients compared with the rest of world.

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