Dataset Information

Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ß-cell function in people with type 2 diabetes.

ABSTRACT:

Aim

Multiple studies support the efficacy of combining a glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in people with type 2 diabetes inadequately controlled on dual/triple oral therapy. Fixed-ratio combinations of basal insulin + GLP-1RA represent a further advance to facilitate management. We assessed the impact of fixed-ratio combination basal insulin + GLP-1RA treatment on β-cell function.

Materials and methods

We analysed data from 351 participants in the LixiLan-G trial (NCT02787551) randomized to receive iGlarLixi (insulin glargine 100 U/ml + lixisenatide) or to continue daily/weekly GLP-1RA, both on top of metformin. Participants received a 2-h meal tolerance test before randomization and at study end (26 weeks), with timed plasma glucose and C-peptide determinations. β-cell function parameters were resolved using mathematical modelling.

Results

In the GLP-1RA group (n = 162), both body weight and glycated haemoglobin decreased at week 26, yet none of the insulin secretion/β-cell function parameters changed significantly. In contrast, in the iGlarLixi group (n = 189), glycated haemoglobin decreased significantly more than in the GLP-1RA group (p < .0001) despite an increase in body weight (+1.7 ± 3.9 kg, p < .0001). Fasting and stimulated insulin secretion decreased at Week 26 (both p < .0001 vs. GLP-1RA), while β-cell glucose sensitivity increased by a median 35% (p = .0032 vs. GLP-1RA). The incremental meal tolerance test glucose area showed a larger reduction with iGlarLixi versus GLP-1RA (p < .0001).

Conclusions

In people with type 2 diabetes on metformin, 26-week treatment with iGlarLixi resulted in a marked improvement in β-cell function concomitant with sparing of endogenous insulin release and a reduction in meal absorption.

SUBMITTER: Ferrannini E

PROVIDER: S-EPMC9314929 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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.