The efficacy and safety of iGlarLixi versus IDegAsp in Chinese people with type 2 diabetes suboptimally controlled with oral antidiabetic drugs: The Soli-D randomized controlled trial.

AIM: To compare the efficacy and safety of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin, insulin degludec plus insulin aspart (IDegAsp), in Chinese people with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drug(s) (OADs). METHODS: In Soli-D, a 24-week, multicentre, open-label, study, insulin-naïve adults were randomized 1:1 to once-daily injections of iGlarLixi (n = 291) or IDegAsp (n = 291), with continued metformin ± sodium-glucose co-transporter-2 inhibitors. The primary endpoint was non-inferiority in HbA1c change from baseline to week 24. Key secondary endpoints included superiority in HbA1c change and body weight (BW) change at week 24. Hypoglycaemia rates were also assessed. RESULTS: At week 24, iGlarLixi showed non-inferiority and superiority over IDegAsp in HbA1c reduction (least squares [LS] mean difference: -0.20 [95% confidence interval {CI}: -0.33, -0.07]; P < .001 for non-inferiority; [97.5% CI: -0.35, -0.05]; P = .003 for superiority). iGlarLixi decreased BW and IDegAsp increased BW from baseline to week 24, with a statistically significant LS mean difference of -1.49 kg in favour of iGlarLixi (97.5% CI: -2.32, -0.66; P < .001). Event rates (per person-year) for American Diabetes Association (ADA) Level 1, 2 or 3 hypoglycaemia were lower for iGlarLixi (1.90) versus IDegAsp (2.72) (relative risk: 0.71; 95% CI: 0.52, 0.98). No ADA Level 3 hypoglycaemia or unexpected safety findings were reported. CONCLUSIONS: In Chinese people with T2D suboptimally controlled with OADs, once-daily iGlarLixi provided better glycaemic control with BW benefit and lower hypoglycaemia event rates versus IDegAsp.

Treatment intensification following glucagon-like peptide-1 receptor agonist in type 2 diabetes: Comparative effectiveness analyses between free vs. fixed combination of GLP-1 RA and basal insulin. RESTORE-G real-world study.

BACKGROUND AND AIMS: Add-on of basal insulin (BI) to intensify the ongoing therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) is recommended, but it is unclear if free or fixed combination of BI and GLP-1 RA produce similar outcomes. A retrospective comparative effectiveness analysis of the add-on of glargine 300 U/mL (Gla-300) to ongoing GLP-1 RA vs. switch to fixed ratio combination of degludec and liraglutide (iDegLira) was performed. METHODS AND RESULTS: Real-world data collected in electronic medical records by 32 Italian diabetes clinics. Propensity score (PS) adjustment was applied to assess changes in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), body weight, and BI dose after 6 months from Gla-300 or iDegLira initiation. Compared to iDegLira group (N = 260), Gla-300+GLP-1 RA group (N = 255) had older age and higher levels of HbA1c (9.1 vs. 8.9%). After 6 months, statistically significant greater FBG improvement [estimated mean difference and 95% confidence intervals: -24.05 mg/dl (-37.04; -11.06; p = 0.0003) and BI dose increase [+0.03 U/kg (95%CI 0.00; 0.06); p = 0.009] were found in the free vs. fixed combination group, although low doses of BI (0.2 U/kg) were reached in both groups. Trends of larger HbA1c and body weight reductions with the free combination were also found, without reaching the statistical significance. CONCLUSION: Although inertia in insulin initiation and titration was documented in both groups, higher benefit on FBG control was obtained with free vs. fixed combination, likely due to a better titration of BI and GLP-1 RA.

iGlarLixi for type 2 diabetes: a systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy and tolerability of iGlarLixi-a novel, fixed-ratio, soluble combination of insulin glargine and lixisenatide-for the treatment of type 2 diabetes (T2D). METHODS: The PubMed, Embase, Cochrane Library and ClinicalTrials.gov databases were searched from inception to November 15, 2023 to identify randomized controlled trials (RCTs) comparing iGlarLixi with a placebo or any other antidiabetic agent in adults with T2D. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated to evaluate the outcomes. RESULTS: A total of 10 trials enrolling 6071 T2D patients were included. Compared with placebos or other antidiabetic agents, iGlarLixi exerted beneficial effects on changes in HbA1c, the percentage of patients who achieved an HbA1c < 7%, the percentage of patients who achieved an HbA1c < 6.5%, the percentage of patients who achieved an HbA1c < 7.0% without weight gain and/or without severe or blood glucose-confirmed hypoglycemic episodes, changes in fasting plasma glucose, and changes in self-measured plasma glucose. Regarding safety, iGlarLixi did not increase the incidence of severe hypoglycemia or serious adverse events but did increase the incidence of gastrointestinal adverse events, symptomatic hypoglycemia, and adverse events (e.g., nausea, vomiting, diarrhea). CONCLUSIONS: iGlarLixi showed improved efficacy and safety in patients with T2D. Additional large, multicenter RCTs are warranted to obtain deeper insights into the efficacy and safety of iGlarLixi, thereby providing guidance for clinical treatment decisions.

The IDEAL (Insulin therapy DE-intensificAtion with iglarLixi) Randomised Controlled Trial-Study Design and Protocol.

INTRODUCTION: Multiple daily injection insulin regimen (MDI) represents the most intensive insulin regimen used in the management of people with type 2 diabetes (PwT2D). Its efficacy regarding glycaemic control is counterbalanced by the increased risk of hypoglycaemia, frequently observed tendency to weight gain and necessity for frequent glucose monitoring. Recent introduction of novel antidiabetic medications with pleiotropic effects reaching far beyond the reduction of glycaemia (HbA1c), such as the glucagon-like peptide 1 receptor agonist (GLP-1 RA), has significantly widened the therapeutic options available for management of T2D. Consequently, there is currently a substantial number of PwT2D for whom the MDI regimen was initiated at a time when no other options were available. Yet, in present times, these individuals could benefit from simplified insulin regimens ideally taking advantage of the beneficial effects of the novel classes of antidiabetic medications. iGlarLixi (Suliqua®) is a once-daily fixed-ratio combination of basal insulin analogue glargine 100 U/ml and a GLP-1 RA lixisenatide. METHODS: Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) is a six-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period examining the efficacy and safety of MDI regimen de-intensification with once-daily administration of iGlarLixi versus MDI regimen continuation in PwT2D on a backgroud therapy with metformin ± sodium-glucose cotransporter 2 inhibitor. PLANNED OUTCOMES: The primary objective is to compare the effects of MDI therapy de-intensification with iGlarLixi versus MDI regimen continuation regarding glycaemic control (HbA1c). Secondary objectives include detailed evaluation of the effects of MDI regimen de-intensification with iGlarLixi on glycaemic control using standardised continuous glucose monitoring (CGM) metrics and self-monitoring of plasma glucose. Furthermore, body weight and body composition analysis, quality of life and safety profile are evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04945070.

Real-world effectiveness and safety of insulin glargine 100 U/mL plus lixisenatide in adults with type 2 diabetes: An international, multicentre, 12-month, prospective observational study.

AIM: To assess the impact of insulin glargine (100 U/mL) and lixisenatide (iGlarLixi) fixed-ratio combination therapy on the overall management of glycaemia in patients with type 2 diabetes (T2D), previously inadequately controlled with oral antidiabetic drugs ± basal insulin or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). MATERIALS AND METHODS: This 12-month, international, multicentre, prospective, observational study included patients (age ≥ 18 years) with T2D who had initiated iGlarLixi within 1 month prior to study inclusion. Data were collected at study inclusion, month 3, month 6 and month 12 from patient diaries, self-measured plasma glucose, and questionnaires. The primary endpoint was change in HbA1c from baseline to month 6. RESULTS: Of the 737 eligible participants (mean age: 57.8 [standard deviation: 11.2] years; male: 49%), 685 had baseline and post-baseline HbA1c data available. The least squares mean change in HbA1c from baseline to month 6 was -1.4% (standard error [95% confidence interval (CI)]: 0.05 [-1.5, -1.3]). The absolute change from baseline at month 12 was -1.7% ± 1.9% (95% CI: -1.9, -1.5). There were 72 hypoglycaemia events reported during the study period, with a very low incidence of severe hypoglycaemia (two participants [rate: 0.003 events per patient-year]). CONCLUSIONS: This real-world observational study shows that initiation of iGlarLixi in people with T2D inadequately controlled on oral antidiabetic drugs ± basal insulin or GLP-1 RAs improves glycaemic control with a low incidence of hypoglycaemia.

Safety and effectiveness of iGlarLixi in adults with type 2 diabetes mellitus from Gulf countries during Ramadan holy month: A subgroup analysis of the SoliRam observational study.

AIM: To investigate safety and effectiveness of iGlarLixi in adults with type 2 diabetes mellitus (T2DM) observing fast during Ramadan from Gulf countries. METHODS: This planned subgroup analysis of the SoliRam - a multinational, prospective, non-interventional, real-world, observational study - focused on participants from Gulf countries. Primary endpoint was proportion of participants experiencing ≥1 episode of severe and/or symptomatic documented (<70 mg/dL [<3.9 mmol/L]) hypoglycemia. RESULTS: A total of 241 individuals with T2DM (mean age: 58.1 years; male: 54.4%; mean duration of diabetes: 13.3 years) were included. All 234 eligible participants followed during Ramadan were able to fast for ≥25 days and no participants broke fast due to hypoglycemia. Primary endpoint was reported in one participant (0.5%) during fasting hours during Ramadan. Improvements (mean ± SD change) in HbA1c (-1.0 ± 1.0% [-11 ± 10 mmol/mol]), FPG (-22.5 ± 29.7 mg/dL), and body weight (-1.5 ± 2.0 kg) were observed from pre-Ramadan to post-Ramadan. Three participants (1.2 %) reported an adverse event (AE) of any cause and one (0.4%) reported a gastrointestinal AE. CONCLUSIONS: iGlarLixi is an effective and well-tolerated treatment in people with T2DM from Gulf countries, including during Ramadan fasting, and is associated with low risk of hypoglycemia.

Impact of Participant Characteristics on Clinical Outcomes with iGlarLixi in Type 2 Diabetes: Post Hoc Analysis of SPARTA Japan.

INTRODUCTION: The real-world SPARTA Japan study confirmed the effectiveness and safety of the fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) once daily over 6 months in Japanese people with type 2 diabetes (T2D). This post hoc analysis examined the impact of participant characteristics on the achievement of age-defined glycaemic targets with iGlarLixi therapy. METHODS: The retrospective, observational SPARTA Japan study included adults with T2D who initiated iGlarLixi. In this analysis, data from insulin-naïve and insulin-experienced participants were separately assessed to compare glycated haemoglobin (HbA1c), body weight and safety outcomes between those who achieved ('achieved' group) and those who did not achieve ('not-achieved' group) age-defined glycaemic targets after 6 months of iGlarLixi. The not-achieved group was further stratified by whether or not their iGlarLixi dose was increased during treatment. RESULTS: In total, 418 participants were included in this analysis (138 insulin naïve and 280 insulin experienced). Among both insulin-naïve and insulin-experienced participants, those in the achieved group were older and had lower baseline HbA1c than those in the not-achieved group. Compared with the not-achieved group, the achieved group showed significantly greater HbA1c reductions from baseline (in both insulin-naïve and insulin-experienced participants) and significantly greater body weight reductions (in insulin-naïve participants), despite some participants in the not-achieved group receiving significantly higher insulin glargine doses than those in the achieved group. In both insulin-naïve and insulin-experienced participants, the incidence of hypoglycaemia and gastrointestinal-related adverse events was similar in the achieved and not-achieved groups. In a multivariate analysis, glycaemic target achievement was significantly more likely in older individuals and those who lost weight during iGlarLixi treatment. CONCLUSIONS: Achievement of age-defined glycaemic targets with iGlarLixi treatment for 6 months was significantly affected by increased age and body weight loss, regardless of prior insulin exposure. TRIAL REGISTRATION: UMIN-CTR Trials Registry, UMIN000044126; registered 10 May 2021.

iGlarLixi is an injectable product used to treat type 2 diabetes that contains a fixed combination of two drugs, insulin glargine (at a concentration of 100 U/mL) and lixisenatide. The SPARTA Japan study investigated the effectiveness of controlling blood glucose levels and the safety of iGlarLixi in Japanese people when taken once daily for over 6 months as part of their routine medical care. The analysis reported in this article looked back at data from SPARTA Japan to assess whether certain characteristics of the people who took part in the study affected how well blood glucose targets were met. People who had previously taken insulin and those who had not were identified, and their results were assessed separately. The people were divided into those who had met their blood glucose level target (with the target defined as the glycated haemoglobin level for each person based on their age) and those who had not met their target. It was found that people who achieved their blood glucose target while receiving iGlarLixi were more likely to be older, to have had a lower glycated haemoglobin level before starting iGlarLixi, and to have lost weight during treatment than those who did not achieve their target, whether or not they had previously been treated with insulin. Side effects of excessively low blood glucose levels or gastrointestinal upset with iGlarLixi treatment occurred in a similar number of people who achieved or did not achieve their blood glucose target.

Effects of age and disease duration on the efficacy and safety of iGlarLixi in Asian people with type 2 diabetes: A post hoc analysis of the LixiLan-O-AP and LixiLan-L-CN trials.

AIM: To evaluate the effect of age and disease duration on the efficacy and safety of iGlarLixi versus insulin glargine 100 units/ml (iGlar) or lixisenatide (Lixi) alone in Asian people with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (LixiLan-O-AP) or basal insulin ± oral antidiabetic drugs (LixiLan-L-CN). MATERIALS AND METHODS: In this post hoc analysis, the glycated haemoglobin (HbA1c) changes were assessed from baseline to week 24 (LixiLan-O-AP) or 30 (LixiLan-L-CN) in subgroups defined by baseline age (<65, ≥65 years) and duration of T2D. The proportion who achieved the composite of HbA1c <7% (<53.0 mmol/mol) without weight gain and without symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L) and the incidences of hypoglycaemia and gastrointestinal disorders were also analysed. RESULTS: HbA1c reductions were consistently greater with iGlarLixi versus iGlar or Lixi across all subgroups, including participants aged ≥65 years and those with T2D for ≥15 or ≥20 years. Greater proportions of participants achieved HbA1c <7% (<53.0 mmol/mol) without weight gain or hypoglycaemia with iGlarLixi versus iGlar or Lixi, regardless of age or T2D duration. Hypoglycaemia incidence was similar with iGlarLixi versus iGlar across most subgroups; the incidence of gastrointestinal disorders was lower with iGlarLixi versus Lixi in all subgroups. CONCLUSIONS: iGlarLixi showed consistent efficacy and safety across all age and disease duration subgroups in Asian people with uncontrolled T2D, including older individuals and those with longstanding disease.

Comparison of efficacy and safety of insulin degludec/liraglutide and insulin glargine U-100/lixisenatide in individuals with type 2 diabetes mellitus using professional continuous glucose monitoring.

AIM/INTRODUCTION: Insulin glargine U100/lixisenatide and insulin degludec/liraglutide are fixed-ratio combinations containing basal insulin and a glucagon-like peptide-1 receptor agonist capable of reducing both fasting and postprandial blood glucose levels with a single formulation. This study aimed to compare the time in range (TIR) and the time below range (TBR) level 1 using professional continuous glucose monitoring and to establish criteria for the differential use of the fixed-ratio combinations. MATERIALS AND METHODS: Thirty-six outpatients with type 2 diabetes mellitus (24 men and 12 women; average age, 62.1 years) were randomly assigned to the groups. At 0 and 18 weeks, a device was worn to compare the TIR and TBR level 1. The correlation between the C-peptide index at baseline and TIR at 18 weeks was assessed. RESULTS: The TIR and TBR level 1 showed no significant differences between the two groups. Both groups showed significant positive correlations between the C-peptide index and the TIR (P = 0.002, r = 0.679; P = 0.002, r = 0.681, respectively). The changes in glycemic variability, therapeutic indices, and body mass index were not significantly different among the groups (P > 0.05). The receiver operating curve analysis revealed that the cut-off values of the C-peptide index to achieve TIR of >70% at 18 weeks were 1.258 (sensitivity, 77.8%; specificity, 100%) and 1.099 (sensitivity, 57.1%; specificity, 90.9%) in the insulin glargine U100/lixisenatide and insulin degludec/liraglutide groups, respectively. CONCLUSIONS: A TIR of >70% was achieved for both fixed-ratio combinations without significant differences.

Advancing type 2 diabetes therapy with iGlarLixi in older people: Pooled analysis of four randomized controlled trials.

AIM: To assess the efficacy and safety of iGlarLixi in older people (≥65 years) with type 2 diabetes (T2D) advancing or switching from oral agents, a glucagon-like peptide-1 receptor agonist (GLP-1RA), or basal insulin. MATERIALS AND METHODS: The data of participants aged <65 years and ≥65 years from four LixiLan trials (LixiLan-O, LixiLan-G, LixiLan-L, SoliMix) were evaluated over 26 or 30 weeks. RESULTS: Participants aged <65/≥65 years (n = 1039/n = 497) had a mean baseline body mass index of 31.4 and 30.7 kg/m2 and glycated haemoglobin (HbA1c) concentration of 66 mmol/mol (8.2%) and 65 mmol/mol (8.1%), respectively. Least squares mean HbA1c change from baseline to end of treatment (EOT) was -14.32 mmol/mol (-1.31%) (95% confidence interval [CI] -14.97, -13.77 [-1.37%, -1.26%]) for those aged <65 years and -13.66 mmol/mol (-1.25%) (95% CI -14.54, -12.79 [-1.33%, -1.17%]) for those aged ≥65 years. At EOT, achievement of HbA1c targets was similar between the group aged <65 years and the group aged ≥65 years: <53 mmol/mol (<7%) (59.0% and 56.5%, respectively), <59 mmol/mol (<7.5%) (75.5% and 73.0%, respectively) and <64 mmol/mol (<8%) (83.8% and 84.1%, respectively). The incidence and event rate of American Diabetes Association Level 1 hypoglycaemia during the studies were also comparable between the two groups: 26.7% and 28.2% and 1.7 and 2.1 events per patient-year for the group aged <65 years and the group aged ≥65 years, respectively. A clinically relevant reduction in HbA1c (>1% from baseline for HbA1c ≥64 mmol/mol [≥8%] or ≥0.5% from baseline for HbA1c <64 mmol/mol [<8%]) without hypoglycaemia was attained by 50.0% and 47.6% of participants aged <65 years and ≥65 years, respectively. Adverse events were similar between the two age groups. CONCLUSIONS: iGlarLixi is a simple, well-tolerated, once-daily alternative for treatment advancement in older people with T2D that provides significant improvements in glycaemic control without increasing hypoglycaemia risk, thus reducing the treatment burden.

Budget Impact Analysis of Intensification with iGlarLixi Compared to Alternative Treatment Strategies Among Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: The clinical benefits of treating patients with type 2 diabetes mellitus (T2DM) with fixed-ratio combination of insulin iGlar (iGlar) plus lixisenatide (iGlarLixi) were demonstrated in clinical trials and real-world evidence studies; however, its cost impact to healthcare payers is unknown. METHODS: A budget impact model was developed from a United States (US) payer's perspective for a hypothetical healthcare plan of 1 million people over a 1-year time horizon. In scenario analysis, patients with uncontrolled glycated hemoglobin (HbA1c) treated with 60 units or less of daily insulin (insulin cohort) or oral antidiabetic drugs (OADs) only (OAD cohort) were intensified to iGlarLixi/rapid-acting insulin (RAI)/glucagon-like peptide 1 receptor agonists (GLP-1RA) or iGlarLixi/iGlar/GLP-1RA, respectively. Model inputs from real-world data (RWD) included baseline market shares, proportion of patients intensifying to respective treatments, and dosing inputs; unit costs were obtained from published literature. One-way sensitivity analyses assessed the impact of individual parameters. RESULTS: Intensification with iGlarLixi resulted in the lowest incremental per member per month (PMPM) budget impact compared to other intensifying drugs (iGlar, RAI, and GLP-1RA). In the insulin cohort, the incremental PMPM cost for intensification with iGlarLixi ($0.03) was the lowest among intensifying drugs; GLP-1RA ($72.20) and RAI ($4.81). Similarly, the incremental PMPM cost for intensification with iGlarLixi was the lowest ($1.25) in the OAD cohort among intensifying drugs; GLP-1RA ($321.65) and iGlar ($114.82). In scenario analyses, when equal market intensification shares for iGlarLixi and GLP-1RA were explored, the incremental PMPM cost for iGlarLixi ($0.03) remained lower than GLP-1RA ($2.28) and RAI ($10.44) in the insulin cohort. CONCLUSIONS: Intensification with iGlarLixi was associated with lower costs compared to other treatment intensifications, as well as overall budget reductions compared to pre-intensification when considering cost savings attributable to reduction in HbA1c; therefore, its inclusion for the treatment of T2DM would represent a budget saving.

Pharmacokinetics and Safety of iGlarLixi in Healthy Chinese Participants: Results of a Phase 1 Randomized Study.

INTRODUCTION: The Chinese Diabetes Society recommends basal insulin and glucagon-like peptide-1 receptor agonists as an add-on therapy to first-line oral antihyperglycemic drugs for people with type 2 diabetes (T2D). Fixed-ratio combination of insulin glargine 100 U/ml (iGlar) and lixisenatide (iGlarLixi) is known to improve glycemic control in adults with T2D. However, the pharmacokinetics of iGlarLixi has not been evaluated in Chinese participants. The present study evaluated pharmacokinetics and safety of two iGlarLixi (10 U/10 µg and 30 U/15 µg) doses following single subcutaneous administration in healthy Chinese participants. METHODS: This was a Phase 1, single-center, open-label, parallel-group, randomized study in healthy Chinese adults who were randomized to receive a single dose of iGlarLixi with either 1:1 (10 U/10 µg) or 2:1 (30 U/15 µg) ratio of iGlar and lixisenatide. Primary objectives include assessment of pharmacokinetics of iGlar in iGlarLixi 30 U/15 µg group and the pharmacokinetics of lixisenatide in both the groups (iGlarLixi 10 U/10 µg and iGlarLixi 30 U/15 µg). Safety and tolerability were also assessed. RESULTS: In iGlarLixi 30 U/15 µg group, iGlar concentrations were low and quantifiable in three of ten participants, while its main metabolite (M1) was quantifiable in all participants, reflecting rapid conversion of iGlar to M1. Median INS-tmax was 14.00 h for iGlar and 13.00 h post-dose for M1. Absorption of lixisenatide was similar in both dose groups with median tmax of 3.25 and 2.00 h post-dose in both groups. The exposure increase was dose proportionate with a 1.5-fold increase in the lixisenatide dose. Adverse events observed were consistent with those previously reported with iGlar or lixisenatide. CONCLUSION: iGlarLixi administration resulted in early absorption of both iGlar and lixisenatide with a good tolerability profile in healthy Chinese participants. These results are consistent with the previously published data from other geographic regions. TRIAL REGISTRATION: U1111-1194-9411.

Clinical Benefits of Treating Patients with Type 2 Diabetes Mellitus with iGlarLixi: A Patient-Level Simulation Study.

INTRODUCTION: The fixed-ratio combination of insulin glargine (iGlar) plus lixisenatide (iGlarLixi) has proven efficacious in clinical trials; however, there is limited evidence of its benefits in a variety of real-world patients with type 2 diabetes mellitus (T2DM) who present in routine clinical practice. METHODS: A large integrated claims and EHR database was used to identify two real-world (RW) cohorts (ages ≥ 18) with T2DM who were eligible for treatment with iGlarLixi. At baseline, the first cohort (insulin cohort) received insulin with or without oral antidiabetic drugs (OADs), and the second cohort (OAD-only cohort) received OADs only. A Monte Carlo patient-level simulation was applied to each cohort based on treatment strategies and efficacies from the LixiLan-L and LixiLan-O trials to estimate reductions in glycated hemoglobin A1C (A1C) and the percentage achieving age-based A1C goals (≤ 7% for ages < 65 and ≤ 8% for ages ≥ 65) at 30 weeks. RESULTS: The RW insulin (N = 3797) and OAD-only (N = 17,633) cohorts differed considerably in demographics, age, clinical characteristics, baseline A1C levels, and background OAD therapies compared to the populations in the Lixilan-L and Lixilan-O trials. Regardless of the cohort description, A1C goals were achieved among 52.6% vs. 31.6% (p < 0.001) of patients in the iGlarLixi vs. the iGlar arms in the insulin cohort simulation, while A1C goals were achieved among 59.9% vs. 49.3% and 32.8% (p < 0.001) of patients in the OAD-only cohort simulation in the iGlarLixi vs. the iGlar and lixisenatide arms, respectively. CONCLUSIONS: Irrespective of the treatment regimen at baseline (insulin vs. OAD only), this patient-level simulation demonstrated that a greater proportion of patients achieved their A1C goals with iGlarlixi compared to iGlar or lixisenatide alone. These findings suggest that the benefits of iGlarLixi extend to clinically distinct RW populations.

Effectiveness and Safety of iGlarLixi in People with Type 2 Diabetes in Adriatic Region Countries: ENSURE-ADR, a Real-World Study.

INTRODUCTION: The efficacy of iGlarLixi, a fixed-ratio combination of basal insulin glargine 100 units/mL (iGlar) and the short-acting GLP-1 RA lixisenatide (Lixi), was established in people with type 2 diabetes (T2D) who were advancing therapy from oral antidiabetic drugs (OADs) and basal insulin (BI). This retrospective study aimed to evaluate the effectiveness and safety of iGlarLixi using real-world data from people with T2D in the Adriatic region countries. METHODS: This was a non-interventional, retrospective, multicenter, cohort study with the collection of pre-existing data at iGlarLixi initiation and after 6 months of treatment in real-world clinical and ambulatory settings. The primary outcome was the change in glycated hemoglobin (HbA1c) at 6 months after iGlarLixi initiation. Key secondary outcomes included the proportion of people achieving HbA1c < 7.0%, the effect of iGlarLixi on fasting plasma glucose (FPG), body weight and body mass index (BMI). RESULTS: In this study, 262 participants (130 in Bosnia and Herzegovina, 72 in Croatia and 60 in Slovenia) initiated treatment with iGlarLixi. The participants had a mean ± SD age of 66.2 ± 7.9 years and the majority were women (58.0%). The mean baseline HbA1c was 8.9 ± 1.7% and the mean body weight was 94.3 ± 18.0 kg. After 6 months of treatment, the reduction in the mean HbA1c was statistically significant (1.11 ± 1.61%, 95% confidence internal [CI] 0.92, 1.31; p < 0.001), and the proportion of participants who achieved HbA1c < 7.0% had significantly increased from baseline (8.0-26.0%, p < 0.001). The change in mean FPG (mmol/L) levels was significant (2.7 ± 4.4 [95% CI 2.1, 3.2; p < 0.001]). The mean ± SD body weight and BMI were significantly reduced by 2.9 ± 4.3 kg (95% CI 2.3, 3.4; p < 0.001) and 1.3 ± 4.4 kg/m2 (95% CI 0.7, 1.8; p < 0.001), respectively. Two serious hypoglycemia episodes and one adverse gastrointestinal effect (nausea) were registered. CONCLUSIONS: This real-world study demonstrated the effectiveness of iGlarLixi for improving glycemic control and decreasing body weight in people with T2D who need to advance therapy from OADs or insulin.

iGlarLixi provides a higher derived time-in-range versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with type 2 diabetes: A post hoc analysis.

AIM: To evaluate the efficacy of iGlarLixi in the Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time-in-ranges calculated from seven-point self-measured blood glucose. METHODS: Two phase III trials were analysed. LixiLan-O-AP was performed in insulin-naive T2D patients (n = 878) randomized to iGlarLixi, glargine 100 units/mL (iGlar) or lixisenatide (Lixi). LixiLan-L-CN was performed in insulin-treated T2D patients (n = 426) randomized to iGlarLixi or iGlar. Changes in derived time-in-ranges from baseline to end-of-treatment (EOT) and estimated treatment differences (ETDs) were analysed. The proportions of patients achieving 70% or higher derived time-in-range (dTIR), 5% or higher dTIR improvement, and the composite triple target (≥ 70% dTIR, < 4% derived time-below-the-range [dTBR] and < 25% derived time-above-the-range [dTAR]) were calculated. RESULTS: The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD1 : 11.45% [95% CI, 7.66% to 15.24%]) or Lixi (ETD2 : 20.54% [95% CI, 15.74% to 25.33%]) in LixiLan-O-AP, and versus iGlar (ETD: 16.59% [95% CI, 12.09% to 21.08%]) in LixiLan-L-CN. In LixiLan-O-AP, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT with iGlarLixi were 77.5% and 77.8%, respectively, higher than with iGlar (61.1% and 75.3%) or Lixi (47.0% and 53.0%). In LixiLan-L-CN, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT were 71.4% and 59.8% with iGlarLixi, greater than with iGlar (45.4% and 39.5%). More patients achieved the triple target with iGlarLixi compared with iGlar or Lixi. CONCLUSION: iGlarLixi achieved greater improvements in dTIR parameters versus iGlar or Lixi in insulin-naïve and insulin-experienced AP people with T2D.

iGlarLixi (insulin glargine 100 U/ml plus lixisenatide) is effective and well tolerated in people with uncontrolled type 2 diabetes regardless of age: A REALI pooled analysis of prospective real-world data.

AIM: To evaluate the effectiveness and safety in routine clinical practice of insulin glargine/lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) according to age. METHODS: Patient-level data were pooled from 1316 adults with T2D inadequately controlled on oral antidiabetic drugs with or without basal insulin who initiated iGlarLixi for 24 weeks. Participants were classified into age subgroups of younger than 65 years (N = 806) and 65 years or older (N = 510). RESULTS: Compared with participants aged younger than 65 years, those aged 65 years or older had a numerically lower mean body mass index (31.6 vs. 32.6 kg/m2 ), a longer median diabetes duration (11.0 vs. 8.0 years), were more likely to receive prior basal insulin (48.4% vs. 43.5%) and had a lower mean HbA1c (8.93% [74.10 mmol/mol] vs. 9.22% [77.28 mmol/mol]). Similar and clinically relevant reductions in HbA1c and fasting plasma glucose from baseline to week 24 of iGlarLixi therapy were observed regardless of age. At 24 weeks, least-squares adjusted mean (95% confidence interval [CI]) change in HbA1c from baseline was -1.55% (-1.65% to -1.44%) in those aged 65 years or older and -1.42% (-1.50% to -1.33%) in those aged younger than 65 years (95% CI: -0.26% to 0.00%; P = .058 between subgroups). Low incidences of gastrointestinal adverse events and hypoglycaemic episodes were reported in both age subgroups. iGlarLixi decreased mean body weight from baseline to week 24 in both subgroups (-1.6 kg in those aged ≥ 65 years and -2.0 kg in those aged < 65 years). CONCLUSIONS: iGlarLixi is effective and well tolerated in both younger and older people with uncontrolled T2D.

Use of iGlarLixi for the Management of Type 2 Diabetes in Japanese Clinical Practice: Prior Treatment Subgroup Analysis of the SPARTA Japan Study.

INTRODUCTION: iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide 1 receptor agonist (GLP-1 RA) lixisenatide, is one option for treatment intensification in individuals with type 2 diabetes (T2D) who are unable to achieve targeted glycaemic control with their current glucose-lowering agent. Real-world data on the impact of prior treatment on the effectiveness and safety of iGlarLixi may be useful to guide individualised treatment decisions. METHODS: This analysis of the 6-month, retrospective, observational SPARTA Japan study compared glycated haemoglobin (HbA1c), body weight and safety for pre-specified subgroups defined by prior treatment: post oral antidiabetic agent (OAD), GLP-1 RA, basal insulin (BI) + OADs (BOT), GLP-1 RA + BI or multiple daily injections (MDI). The post BOT and MDI subgroups were further divided on the basis of prior dipeptidyl peptidase 4 inhibitor (DPP-4i) use, and the post MDI group was divided on the basis of whether participants continued bolus insulin. RESULTS: Of the 432 participants in the full analysis set (FAS), 337 were included in this subgroup analysis. Across subgroups, mean baseline HbA1c ranged from 8.49% to 9.18%. iGlarLixi significantly (p < 0.05) reduced mean HbA1c from baseline in all but the post GLP-1 RA + BI group. At 6 months, these significant reductions ranged from 0.47% to 1.27%. Prior DPP-4i exposure had no impact on the HbA1c-lowering effect of iGlarLixi. Mean body weight decreased significantly in the FAS (0.5 kg) and the post BOT (1.2 kg) and MDI (1.5 and 1.9 kg) subgroups but increased in the post GLP-1 RA subgroup (1.3 kg). iGlarLixi treatment was generally well tolerated, with very few participants discontinuing because of hypoglycaemia or gastrointestinal events. CONCLUSION: In participants with suboptimal glycaemic control on various regimens, 6 months of iGlarLixi treatment improved HbA1c in all but one prior treatment subgroup (GLP-1 RA + BI), and was generally well tolerated. TRIAL REGISTRATION: UMIN-CTR Trials Registry, UMIN000044126; registered 10 May 2021.

Despite initially receiving oral treatment for their diabetes, many individuals with type 2 diabetes are unable to achieve their blood glucose targets and require treatment intensification as their disease progresses. In these individuals, options for treatment intensification include adding an injectable therapy, such as a glucagon-like peptide 1 receptor agonist or basal insulin, or the combination of both. However, the impact of previously received treatments on the ability of treatment intensification to improve outcomes in these individuals has yet to be evaluated. Here, we report the findings of an analysis that aimed to determine the influence of different treatment backgrounds on the effectiveness and safety of iGlarLixi, a fixed-ratio combination (i.e. combined as a single subcutaneous injection) of the glucagon-like peptide 1 receptor agonist lixisenatide and basal insulin glargine 100 U/mL, in Japanese individuals with type 2 diabetes. We found that iGlarLixi improved glycaemic control and was well tolerated in most individuals, regardless of previously received treatments. These results suggest that iGlarLixi may offer an effective option for improving outcomes in Japanese individuals with type 2 diabetes who require treatment intensification.

iGlarLixi versus premixed insulin initiation in adults with type 2 diabetes advancing from basal insulin therapy: The SoliComplex real-world study.

AIM: To compare outcomes in adults with type 2 diabetes (T2D) suboptimally controlled with basal insulin who initiated treatment with iGlarLixi or premixed insulin. METHODS: This retrospective real-world analysis was conducted using data from adults (age ≥ 18 years) with T2D in the US Optum Clinformatics database who had previously received basal insulin and newly initiated iGlarLixi or premixed insulin. Cohorts were propensity-score matched on baseline characteristics using a greedy nearest neighbour-matching algorithm, and outcomes were assessed at 12 months. Subgroup analyses were performed for those aged 65 years or older and those with a baseline HbA1c of 9% or higher. The primary endpoint was treatment persistence in the overall population. Secondary endpoints were treatment adherence, healthcare resource utilization (HRU), costs, hypoglycaemia events and change in HbA1c from baseline. RESULTS: Each cohort comprised 834 participants. In the overall population, treatment persistence at 12 months was statistically significantly higher for iGlarLixi versus premixed insulin: 42.5% versus 39.1%; hazard ratio 0.88; 95% confidence interval 0.778-0.998; P = .0465. Adherence and HbA1c reduction were similar between groups, whereas hypoglycaemia events, HRU and costs were numerically lower for iGlarLixi. Outcomes in both the age 65 years or older subgroup and in those with an HbA1c of 9% or higher were consistent with those for the overall population. CONCLUSIONS: In this observational study in people with T2D suboptimally controlled on basal insulin, once-daily iGlarLixi was an effective treatment alternative to premixed insulin with significantly higher treatment persistence, similar adherence and HbA1c reduction, and numerically lower hypoglycaemia events, HRU and costs, regardless of age or baseline HbA1c.

Real-world safety and effectiveness of iGlarLixi in people with type 2 diabetes who fast during Ramadan: The SoliRam observational study.

BACKGROUND AND AIMS: To evaluate the safety and effectiveness of iGlarLixi in adults with type 2 diabetes (T2D) fasting during Ramadan. METHODS: SoliRam was a multinational, prospective, single-arm, real-world observational study conducted during Ramadan 2020 and 2021 in adults with T2D treated with iGlarLixi ≥3 months at study entry. The primary endpoint was the percentage of participants experiencing ≥1 episode of severe and/or symptomatic documented hypoglycemia (<70 mg/dL [<3.9 mmol/L]). RESULTS: Among the 409 eligible participants followed during Ramadan, 96.8% fasted for ≥25 days and 92.4% did not break fasting during Ramadan. Four participants broke their fast due to hypoglycemia. Minimal adjustments were seen in antihyperglycemic therapies from pre to during Ramadan. Documented symptomatic hypoglycemia was experienced by 1.0%, 2.3%, and 0.3% of participants, respectively, during the last month of pre-Ramadan, Ramadan, and first month post-Ramadan. Mean change in HbA1c from pre-to post-Ramadan periods was -0.75% (-8.2 mmol/mol), and participants with HbA1c <7% (<53 mmol/mol) increased from 7.9% pre-Ramadan to 28.6% post-Ramadan. CONCLUSIONS: iGlarLixi is an effective and well-tolerated therapy for people with T2D, including those who intend to fast during Ramadan, and is associated with a low risk of hypoglycemia; benefits were observed both during and after Ramadan.