Fixed-ratio Combination Of Insulin Glargine Research Articles

Impact of Participant Characteristics on Clinical Outcomes with iGlarLixi in Type2 Diabetes: Post Hoc Analysis of SPARTA Japan.

The real-world SPARTA Japan study confirmed the effectiveness and safety of the fixed-ratio combination of insulin glargine 100U/mL plus lixisenatide (iGlarLixi) once daily over 6months in Japanese people with type2 diabetes (T2D). This post hoc analysis examined the impact of participant characteristics on the achievement of age-defined glycaemic targets with iGlarLixi therapy. 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 6months of iGlarLixi. The not-achieved group was further stratified by whether or not their iGlarLixi dose was increased during treatment. 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. Achievement of age-defined glycaemic targets with iGlarLixi treatment for 6months was significantly affected by increased age and body weight loss, regardless of prior insulin exposure. UMIN-CTR Trials Registry, UMIN000044126; registered 10 May2021.

794-P: Effectiveness and Safety of iGlarLixi in People with Type 2 Diabetes (Pw2D), Not at Target on Basal Insulin (BI) and Oral Antidiabetic Therapy (BOT)—Results from the Observational, Prospective Study CHANCE

iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, is a once-daily treatment advancement option for Pw2D not at target on BOT. CHANCE investigated effectiveness and safety of switching the BI to iGlarLixi in daily clinical practice. Primary objective was to assess absolute change in HbA1c 24 weeks (W24) after switching to iGlarLixi. Secondary objectives included changes in fasting plasma glucose (FPG), bodyweight (BW), use of oral antidiabetic drugs (OADs), dose of previous BI, and hypoglycemia incidence. Overall, data from 70 Pw2D were analyzed. Mean BI dose was 38.9 units per day and individual target HbA1c was 6.9%. iGlarLixi was started with 30 dose steps per day (DS/d); at W24, mean dose was 41.6 DS/d. HbA1c decreased by -0.7% (P < 0.001), while FPG trended down by ~20 mg/dL. This was accompanied by a -3.0 kg decrease in BW (P = 0.442). Numbers of OADs used decreased markedly 24 weeks after switching to iGlarLixi (P < 0.05). Hypoglycemia incidence was low before and did not change significantly after switching to iGlarLixi. In conclusion, advancing BOT by switching the BI to iGlarLixi, improved glycemic control of Pw2D in daily clinical practice without BW gain and with low hypoglycemia incidence; however, titration was not sufficient to reach glycemic targets after 24 weeks. Disclosure T.Wiesner: Advisory Panel; Roche Diabetes Care, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Sanofi-Aventis Deutschland GmbH, Lilly Diabetes, Boehringer Ingelheim Inc., Abbott Diabetes, Novo Nordisk, Dexcom, Inc., Novartis. M.Pfohl: Advisory Panel; Boehringer Ingelheim and Eli Lilly Alliance, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Sanofi-Aventis Deutschland GmbH. K.Pegelow: Employee; Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Sanofi-Aventis Deutschland GmbH. J.Müller: Employee; Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Bayer Inc., Inmunebio Inc. J.Seufert: Advisory Panel; Abbott Diabetes, Boehringer Ingelheim Pharma GmbH&Co.KG, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Abbott Diabetes, Bayer Inc., Boehringer Ingelheim Pharma GmbH&Co.KG, Merck Sharp & Dohme Corp., Sanofi-Aventis Deutschland GmbH, Novartis, Novo Nordisk. Funding Sanofi-Aventis Deutschland GmbH

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

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/10μg and 30 U/15μg) doses following single subcutaneous administration in healthy Chinese participants. 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/10μg) or 2:1 (30 U/15μg) ratio of iGlar and lixisenatide. Primary objectives include assessment of pharmacokinetics of iGlar in iGlarLixi 30 U/15μg group and the pharmacokinetics of lixisenatide in both the groups (iGlarLixi 10 U/10μg and iGlarLixi 30 U/15μg). Safety and tolerability were also assessed. In iGlarLixi 30 U/15μg 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 14.00h for iGlar and 13.00h post-dose for M1. Absorption of lixisenatide was similar in both dose groups with median tmax of 3.25 and 2.00h 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. 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. U1111-1194-9411.

The Wedding Bells Sound Really Good! iGlarLixi Fixed-Ratio Combination in the Treatment of Type2 Diabetes: A Narrative Review.

iGlarLixi is a fixed-ratio combination of insulin glargine 100U/mL and lixisenatide used in the treatment of type2 diabetes. iGlarLixi has proven clinical benefits in terms of glycemia, weight control, and safety, defined by the risk of hypoglycemia. It simultaneously targets many pathophysiologic abnormalities which are at the root of type2 diabetes and thus presents a complementary mode of action. Finally, it may also address diabetes treatment burden, and, by decreasing the complexity of treatment, it may improve patient adherence and persistence and fight against clinical inertia. This article reviews the results of major randomized controlled trials in people with type2 diabetes that compared iGlarLixi to other therapeutic regimens, representing different intensification strategies, such as basal supported oral therapy, oral antidiabetic drugs, and a combination of the latter with glucagon-like peptide1 receptor agonists. Moreover, as a supplement to randomized trials, data from real-world evidence have also been included.

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

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. 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 30weeks. 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. 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.

Use of iGlarLixi for the Management of Type2 Diabetes in Japanese Clinical Practice: Prior Treatment Subgroup Analysis of the SPARTA Japan Study.

iGlarLixi, a fixed-ratio combination of insulin glargine 100U/mL and the glucagon-like peptide1 receptor agonist (GLP-1 RA) lixisenatide, is one option for treatment intensification in individuals with type2 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. 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 peptidase4 inhibitor (DPP-4i) use, and the post MDI group was divided on the basis of whether participants continued bolus insulin. 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 6months, 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 (0.5kg) and the post BOT (1.2kg) and MDI (1.5 and 1.9kg) subgroups but increased in the post GLP-1 RA subgroup (1.3kg). iGlarLixi treatment was generally well tolerated, with very few participants discontinuing because of hypoglycaemia or gastrointestinal events. In participants with suboptimal glycaemic control on various regimens, 6months of iGlarLixi treatment improved HbA1c in all but one prior treatment subgroup (GLP-1 RA + BI), and was generally well tolerated. UMIN-CTR Trials Registry, UMIN000044126; registered 10 May 2021.

Findings for iGlarLixi versus BIAsp 30 confirmed in groups of people with type 2 diabetes with different biomedical characteristics.

To report prespecified and post hoc analyses of the SoliMix dataset exploring the impact of baseline participant characteristics on the original SoliMix study outcomes, to enable informed treatment choices for people with different biomedical characteristics. SoliMix (EudraCT 2017-003370-13) compared once-daily iGlarLixi (a fixed-ratio combination of insulin glargine 100 U/mL and the glucagon-like peptide-1 receptor agonist lixisenatide) with twice-daily BIAsp 30 (30% insulin aspart and 70% insulin aspart protamine). In this analysis, the original primary outcomes of noninferiority of iGlarLixi versus BIAsp 30 in terms of glycated haemoglobin (HbA1c) change and superiority in terms of body weight change, together with change in basal insulin dose and hypoglycaemia outcomes, were investigated by baseline age, duration of diabetes, insulin dose, HbA1c level, body mass index (BMI), and renal function. No evidence of difference in comparative treatment effect was detected across baseline age, duration of diabetes, insulin dose, HbA1c level, BMI and renal function subgroups for any endpoint (all heterogeneity P> 0.05), except American Diabetes Association Level 2 hypoglycaemia event rate when stratified by insulin dose (P= 0.011), which may be a chance difference given multiple testing and the small numbers of Level 2 events. Treatment effects of iGlarLixi were consistent irrespective of baseline HbA1c, insulin dose, BMI, age, duration of diabetes and renal function, supporting the use of iGlarLixi as an efficacious and well-tolerated treatment option in people with type 2 diabetes with a wide range of biomedical characteristics.

Effectiveness, Safety, and Appropriateness in the Use of the Fixed-Ratio Combination of Insulin Glargine and Lixisenatide in Type 2 Diabetes: The ENSURE Retrospective Real-World Study.

Pivotal trials documented glycemic benefits of fixed-ratio combination of insulin glargine 100U/mL and lixisenatide (iGlarLixi), with no weight gain and low hypoglycemia risk in type 2 diabetes (T2D). This study aimed at assessing effectiveness and patterns of use of iGlarLixi in a real-world setting. This was a retrospective, multicenter, study, based on electronic medical records. All patients initiating iGlarLixi from May 2018 to July 2020 were considered. Overall, 25 centers provided data on 675 patients initiating iGlarLixi with the following characteristics: age 66.4 ± 10.1years, 54.2% men, T2D duration 15.5 ± 11.5years, HbA1c 8.6 ± 1.4%, body mass index (BMI) 30.8 ± 5.3kg/m2, 45.1% already treated with basal insulin, and 21.9% with basal bolus (± oral hypoglycemic agents). Metformin and sodium-glucose cotransporter-2 inhibitors were used in 76.0% and 0.9% of patients, respectively. Combinations of iGlarLixi with other glucose-lowering drugs such as sulfonylureas or short-acting insulin were found in 32.4% of patients. Effectiveness of iGlarLixi (N = 184) showed that HbA1c declined by 0.77% [95% confidence interval (CI) -1.00, -0.54] after 6months. In combination with metformin and/or SGLT-2i (N = 117), HbA1c declined by -0.92% (95% CI -1.22, -0.62) and weight significantly decreased by 1.21kg. iGlarLixi dose was suboptimally titrated. Safety data (N = 171) showed incidence rates of blood glucose ≤ 70 and < 54mg/mL of 0.26 and 0.05 events per person-month during 6months, respectively, with a risk reduction of about 75% with respect the 6months before iGlarLixi initiation. No severe hypoglycemia was reported. In adults with T2D, effectiveness and safety of iGlarLixi were documented in a real-world setting; appropriateness of use and adequate titration should be urgently improved so that clinical practice outcomes become more comparable to clinical trials results. Further real-world studies on the effect of iGlarLixi therapy are warranted.

Real-world evidence on the use of a fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) in people with suboptimally controlled type 2 diabetes in Romania: a prospective cohort study (STAR.Ro).

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.

Randomized Comparison of Initiating the Fixed-Ratio Combination of iGlarLixi or Biosimilar Insulin Glargine Together With Gliclazide in Participants of South Asian Origin With Type 2 Diabetes: VARIATION 2 SA Trial

ObjectivesThe objective of this study was to compare initiation of a fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) vs insulin glargine U100 (iGlar) along with gliclazide, exclusively in people of South Asian origin with type 2 diabetes (T2D). MethodsThe Variability of glucose Assessed in a Randomized trial comparing the Initiation of A Treatment approach with biosimilar basal Insulin analog Or a titratable iGlarLixi combinatioN in type 2 diabetes among South Asian participants (VARIATION 2 SA) trial (ClinicalTrials.gov identifier: NCT03819790) randomized insulin-naïve adults with T2D having glycated hemoglobin (A1C) 7.1% to 11% to initiate either iGlarLixi or iGlar + gliclazide. Insulin doses were titrated similarly to a prebreakfast glucose target of 4.0 to 5.5 mmol/L. Average time in range (TIR) on a masked continuous glucose monitor (CGM), A1C, fasting plasma glucose (FPG) and weight were assessed at the end of the 12-week treatment period. ResultsMean baseline characteristics for the 104 randomized participants were similar between treatment groups, including the following: age, 59±11 years; diabetes duration, 13.7±7.3 years; and A1C, 8.5%±1.2%. Coprimary outcomes of average TIRs within 24- and 12-h (6 am to 6 pm) periods at the end of trial were 70.5%±16.8% and 72.9%±17.6% for iGlarLixi, whereas these TIRs were 65.6%±21.6% and 67.3%±20.7% for the iGlar + gliclazide regimen, respectively, with no significant differences between groups (p=0.35 for 24-h TIR and p=0.14 for 12-h TIR). No significant difference in secondary outcomes was observed between treatment groups. Self-reported hypoglycemic events throughout the trial period and CGM-reported hypoglycemia (<4 and <3 mmol/L) were similar between randomized treatments. ConclusionsInitiation of iGlarLixi resulted in similar TIR, A1C, FPG, weight and hypoglycemia compared with the more affordable option of starting iGlar + gliclazide in adults of South Asian origin with T2D.

Efficacy of iGlarLixi on 5-year risk of diabetes-related complications: A simulation study

ObjectiveThis study simulated the 5-year risk of diabetes complications associated with the use of iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/ml and lixisenatide, in type 2 diabetes (T2D) using the BRAVO diabetes model. MethodsThe six-month efficacy data of iGlarLixi and Standard of Care (SOC) were extracted from the LixiLan-O (NCT02058147) and ORIGIN (NCT00069784) trials, respectively. The trial participants' baseline characteristics were standardized to the ACCORD trial through a matching method. The BRAVO diabetes simulation model was used to project the 5-year complications based on T2D people baseline characteristics and treatment efficacy. An optimistic scenario where the six-month relative efficacy of iGlarLixi (i.e., iGlarlixi-SOC) lasted for 5 years, and a conservative scenario where the relative effect of iGlarLixi waned to none within 5 years were simulated. ResultsiGlarLixi compared with SOC was found to reduce HbA1c (−1.4%), SBP (−3.4 mm Hg), and BMI (−0.6 kg/m2) in six months. We simulated a 5-year risk reduction in major adverse cardiovascular events (MACE) (relative risk [RR] 0.77, 95% CI: 0.67–0.88), and all-cause mortality (RR 0.94, 95% CI: 0.92–0.96) under an optimistic scenario, and MACE (RR 0.86, 95% CI: 0.75–0.96), and all-cause mortality (RR 0.96, 95% CI: 0.92–0.98) under a conservative scenario. ConclusionsThe long-term use of iGlarLixi may lead to a substantial reduction in diabetes-related complications among people with T2D at elevated risk for CVD. The use of a simulation model to evaluate outcomes of treatment in a well-characterized patient cohort is novel. Such an approach may serve as a template for future evaluation of medications and combinations when the effect of a treatment is known, but a long-term outcome trial is not feasible.

Concomitant iGlarLixi and Sodium-Glucose Co-transporter-2 Inhibitor Therapy in Adults with Type 2 Diabetes: LixiLan-G Trial and Real-World Evidence Results

IntroductioniGlarLixi, the once-daily fixed-ratio combination of insulin glargine 100 U/ml and lixisenatide, robustly improves glycaemic control in adults with type 2 diabetes irrespective of previous treatment [oral antihyperglycaemic drugs (OADs), basal insulin or glucagon-like peptide-1 receptor agonists (GLP-1 RAs)]. Sodium-glucose co-transporter-2 inhibitors (SGLT2is) are a recommended treatment option for people with type 2 diabetes with cardiovascular disease, kidney disease and/or heart failure because of their cardio- and renoprotective benefits. Herein, we assessed the effects of concomitant iGlarLixi and SGLT2i therapy.MethodsWe conducted subgroup analyses according to SGLT2i use in: (1) adults with suboptimally controlled type 2 diabetes on GLP-1 RAs and OADs switching to iGlarLixi in the 26-week LixiLan-G randomised controlled trial (RCT; NCT02787551) and (2) adults switching to or adding iGlarLixi in a 6-month, retrospective real-world evidence (RWE) observational study using data from the US Optum-Humedica electronic medical records database. Changes in HbA1c and hypoglycaemia prevalence and event rates were assessed.ResultsThere were no major differences in baseline characteristics for those who initiated iGlarLixi while already using SGLT2i (n = 346) and those initiating iGlarLixi without concomitant SGLT2i therapy (n = 1285). HbA1c reductions from baseline to time of assessment and hypoglycaemia prevalence and event rates were similar for iGlarLixi users regardless of SGLT2i therapy.ConclusionEvidence from an RCT and an RWE analysis supports the efficacy/effectiveness and safety of iGlarLixi when used concomitantly with SGLT2i.Trial RegistrationNCT02787551.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01180-1.

Effectiveness of IGlarLixi, a Fixed-Ratio Combination of Insulin Glargine 100 U/mL and Lixisenatide, in People with Type 2 Diabetes.

IntroductionThe latest Position Statement of the American Diabetes Association/European Association for the Study of Diabetes proposes the use of a fixed-ratio combination (FRC) of a long-acting basal insulin and a glucagon-like peptide-1 receptor agonist as part of treatment intensification. This study aimed to assess the effectiveness of the insulin glargine + lixisenatide (iGlarLixi) FRC on glycaemic control and hypoglycaemia in real-life settings.MethodsThis non-interventional, 26-week study included participants aged 18–80 years with suboptimally controlled type 2 diabetes (T2D) using oral antidiabetics (OADs) ± basal insulin therapy. The primary efficacy endpoint was the proportion of participants who achieved at least a 1% decrease in glycated haemoblobin (HbA1c) level from baseline to week 26.ResultsOf the 441 participants eligible for entry into the study, 353 were included in the efficacy analyses. These individuals were switched from OADs without (282 [79.9%]) or with (71 [20.1%]) insulin-based treatment. A reduction in HbA1c of at least 1.0% (primary endpoint) was achieved by 215 subjects (60.9%). All glycaemic variables (mean ± standard deviation) improved significantly during follow-up (HbA1c, from 8.9 ± 1.31 to 7.4 ± 0.97%; fasting blood glucose, from 9.0 ± 2.18 to 6.9 ± 1.23 mmol/L; postprandial blood glucose, from 11.3 ± 2.33 to 8.5 ± 1.46 mmol/L; p < 0.001 for all). Body weight also decreased during follow-up, from 90.5 ± 18.03 to 88.2 ± 17.75 kg (p < 0.001). Overall, 41 participants (9.3% of the safety population) self-reported 101 non-severe hypoglycaemic episodes (incidence rate 0.498 events/person-year). There were no severe hypoglycaemic episodes reported. Gastrointestinal adverse events were reported by five participants (1.1% of the safety population). The vast majority (96.6%) of the study population continued iGlarLixi treatment after the final visit.ConclusionThe results of this non-interventional study confirmed the efficacy results of the randomized controlled trial programme of the iGlarLixi FRC in a real-life setting. iGlarLixi significantly improved glycaemic control in association with a low frequency of hypoglycaemia and gastrointestinal adverse events in a heterogeneous population of participants with T2D suboptimally controlled with OADs ± basal insulin.

234-OR: Advancing Therapy in Uncontrolled Basal Insulin-Treated Type 2 Diabetes (T2D): Better Clinical Outcomes with IGlarLixi vs. Premix 70/30 in the SoliMix Trial

Introduction: iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, offers an alternative treatment advancement option to premix insulin for uncontrolled basal insulin-treated T2D. SoliMix, an open-label, multicenter study, was the first to compare these two insulin coformulations.Methods: SoliMix randomized adults with T2D and HbA1c ≥7.5-≤10 % on basal insulin + oral antihyperglycemic drugs (OADs) to once-daily iGlarLixi or twice-daily premix insulin 70/30 analogue (BiAsp 70/30). Co-primary efficacy endpoints were non-inferiority in HbA­1c reduction or superiority in bodyweight change from baseline to Week 26 of iGlarLixi vs. BiAsp 70/30.Results: Both co-primary efficacy endpoints were met (Table), as well as iGlarLixi superiority vs. BiAsp 70/30 in HbA1c reduction. Significantly more participants reached HbA1c <7 % without weight gain, and HbA1c <7 % without weight gain and without hypoglycemia, in the iGlarLixi group than the BiAsp 70/30 arm. Incidence and rates of hypoglycemia (Level 1 or 2) were lower with iGlarLixi vs. BiAsp 70/30.Conclusions: Based on better glucose control with weight benefit and less hypoglycemia, once-daily iGlarLixi is a favorable alternative to twice-daily premix 70/30 for advancing therapy in people with T2D uncontrolled on basal insulin + OADs.View largeDownload slideView largeDownload slide DisclosureJ. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. N. Demil: Employee; Self; Sanofi. M. Bonnemaire: Employee; Self; Sanofi. R. J. Mccrimmon: Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis, Board Member; Self; Novo Nordisk Foundation, Research Support; Self; AstraZeneca. R. Emral: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Sanofi. L. Sauque-reyna: None. V. Mohan: None. C. Trescoli: None. S. N. Al sifri: None. N. Lalic: None. A. Alvarez: Employee; Self; Sanofi. P. Picard: None.FundingSanofi (EudraCT 2017-003370-13)

364-P: Efficacy of IGlarLixi on Five-Year Risk of Diabetes-Related Complications: A Simulation Experiment

This study assessed the 5-year risk of diabetes complications of iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/ml and lixisenatide, in type 2 diabetes (T2Ds) using a simulation model. The six-month efficacy data of iGlarLixi and Standard of Care (SOC) were extracted from the LixiLan-O trial and ORIGIN trial, and patients’ baseline characteristics were standardized to the ACCORD trial. The BRAVO diabetes simulation model was used to project the 5-year complications based on patients’ baseline characteristics and treatment efficacy. An optimistic scenario where the six-month relative efficacy of iGlarLixi (i.e., iGlarlixi-SOC) lasted for 5 years, and a conservative scenario where the relative effect of iGlarLixi waned to none within 5 years were simulated. iGlarLixi was found to reduce HbA1c (-1.4%), SBP (-3.4 mmHg), and BMI (-0.6 kg/m2) in six-month, compared with SOC. We found a 5-year risk reduction in major adverse cardiovascular events (MACE) (relative risk [RR] 77.1%, 95% CI: 66.9%-88.2%), and all-cause mortality (RR 94.0%, 95% CI:92.4%-96.3%) under an optimistic scenario, and MACE (RR 85.5%, 95% CI: 74.7%-96.3%), and all-cause mortality (RR 95.7%, 95% CI:92.1%-98.1%) under a conservative scenario (See Table for other outcomes). The long-term use of iGlarLixi may lead to a substantial reduction in diabetes-related complications among people with T2D at elevated risk for CVD. Disclosure H. Shao: Research Support; Self; Sanofi. H. Kianmehr: None. P. Li: None. V. Fonseca: Consultant; Self; Abbott Diabetes, Asahi Kasei Corporation, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health. L. Shi: Research Support; Self; AstraZeneca, Sanofi. Funding Sanofi (2020-1487)

Translating iGlarLixi Evidence for the Management of Frequent Clinical Scenarios in Type 2 Diabetes.

Treatment of type 2 diabetes (T2D) requires progressive therapy intensification to reach and maintain individualized glycemic targets. iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide (Lixi), has been shown to provide robust HbA1c reductions allowing more people to reach HbA1c targets compared with separate administration of iGlar or Lixi. The purpose of this review is to help clinicians understand treatment intensification using iGlarLixi by presenting typical clinical scenarios supported by research evidence. These cases will focus on individuals with T2D inadequately controlled by oral antihyperglycemic drugs, basal insulin, or glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and take into consideration T2D duration, body mass index, incidence of adverse events, and regimen simplicity. Clinical evidence on the efficacy, effectiveness, and safety of iGlarLixi from randomized controlled trials and real-world studies will be discussed in the context of these cases.

Durable Effects of iGlarLixi Up to 52 Weeks in Type 2 Diabetes: The LixiLan-G Extension Study.

OBJECTIVEIn the LixiLan-G trial, switching to iGlarLixi, a once-daily titratable fixed-ratio combination of insulin glargine 100 units/mL and the glucagon-like peptide 1 receptor agonist (GLP-1 RA) lixisenatide, improved glucose control in type 2 diabetes uncontrolled with GLP-1 RAs over 26 weeks versus continuing prior GLP-1 RA. A prespecified, 26-week, single-arm extension of LixiLan-G aimed to determine the durability of iGlarLixi efficacy and safety over 52 weeks.RESEARCH DESIGN AND METHODSParticipants with type 2 diabetes uncontrolled by GLP-1 RAs (glycated hemoglobin [HbA1c] 7–9% [53–75 mmol/mol]) were initially randomized to switch to iGlarLixi or continue prior GLP-1 RA. Those randomized to iGlarLixi who completed the 26-week primary end point period could continue iGlarLixi open-label treatment over a 26-week extension to assess durability of efficacy and safety.RESULTSGlycemic control achieved with iGlarLixi at week 26 (mean HbA1c 6.7% [50 mmol/mol]) was maintained at week 52 (mean HbA1c 6.7% [50 mmol/mol]; mean ± SD change from baseline at week 52: −1.0 ± 0.9% [11 ± 10 mmol/mol]). Proportions of participants reaching HbA1c <7% (53 mmol/mol) with iGlarLixi were similar at week 26 (62%) and 52 (64%), as were those reaching this target without documented symptomatic (<3.0 mmol/L) hypoglycemia (57% and 58%). Safety of iGlarLixi was similar at weeks 26 and 52, with low rates of documented symptomatic hypoglycemia and gastrointestinal events.CONCLUSIONSThe efficacy and safety of iGlarLixi at the end of the 26-week randomized treatment period was maintained over the 26-week extension period in the LixiLan-G trial.

Insulin glargine/lixisenatide fixed-ratio combination (iGlarLixi) compared with premix or addition of meal-time insulin to basal insulin in people with type 2 diabetes: A systematic review and Bayesian network meta-analysis.

To assess the efficacy and safety of iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, relative to premix insulin and other insulin options through network meta-analysis. A systematic literature search identified randomized controlled trials (RCTs) comparing iGlarLixi, premix insulin or basal insulin (BI) in combination with meal-time insulin, in people inadequately controlled with BI. Eligible RCTs were compared using Bayesian network meta-analysis. Eight RCTs, some open-label, involving 3538 participants, with a study duration of 24-30 weeks were included. The estimated difference in HbA1c reduction with iGlarLixi compared with premix insulin was -0.50%-units (95% credible interval: -0.93 to -0.06) with 98% probability of iGlarLixi being superior to premix. Estimates for iGlarLixi versus meal-time + BI (thrice-daily meal-time insulin + basal) and basal-plus (once-daily meal-time insulin + BI) were -0.35 (-0.89 to +0.13)%-units and -0.68 (-1.18 to -0.17)%-units with probabilities of real difference of 94% and 99%, respectively. Safety outcome analysis suggested that iGlarLixi had lower rates of both confirmed and documented symptomatic hypoglycaemia compared with premix insulin (probabilities of 85% and 93%, respectively) and lower weight gain (probability 98%). iGlarLixi showed similar or improved efficacy and safety versus other intensification choices from BI included in this study, providing a clinically relevant treatment option in people with type 2 diabetes not well controlled on BI.

88-LB: Similar Efficacy and Safety of IGlarLixi When Initiated in Patients with Type 2 Diabetes (T2D) with or without Concomitant Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) Use in a Randomized Controlled Trial (RCT) and Real-World Setting

iGlarLixi, the once-daily fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, has been shown to robustly improve glycemic control in adults with T2D. To assess the effects of iGlarLixi with SGLT2i in T2D, we conducted subgroup analyses according to SGLT2i use in the following populations: 1) adults uncontrolled on GLP-1 receptor agonists (GLP-1 RAs) and oral antidiabetic drugs (OADs) switching to iGlarLixi in the 26-week LixiLan-G RCT (NCT02787551) and 2) adults switching to or adding iGlarLixi in a 6-month, retrospective real-world observational study using data from the U.S. Optum-Humedica electronic medical records database. Endpoints included change in HbA1c and hypoglycemia incidence and event rates. Across the studies, there were no major differences in baseline characteristics for those who initiated iGlarLixi while already using SGLT2i (N=346) and those initiating iGlarLixi without background SGLT2i use (N=1285). HbA1c reductions from baseline to week 26 and hypoglycemia incidence and event rates were similar for iGlarLixi regardless of SGLT2i use (Table). In conclusion, evidence from both RCT and real-world clinical settings support the efficacy and safety of iGlarLixi when used in combination with SGLT2i. Disclosure J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc., REMD Biotherapeutics. Other Relationship; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Ali: Advisory Panel; Self; Eli Lilly and Company, Napp Pharmaceuticals, Novo Nordisk A/S, Sanofi. Research Support; Self; Eli Lilly and Company, Gelesis. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Stock/Shareholder; Self; Amarin Corporation. J.J. Meier: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. F. Giorgino: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Roche Diabetes Care, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., LifeScan, Inc., MedImmune, Merck Sharp &amp; Dohme Corp., Roche Diabetes Care, Sanofi. Research Support; Self; Eli Lilly and Company, LifeScan, Inc., Takeda Development Centre Europe Ltd. C. Guja: Advisory Panel; Self; AstraZeneca, Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Servier. M. Prazny: Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Roche Diabetes Care. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd. R. Lubwama: Employee; Self; Sanofi US. E. Souhami: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Blonde: Advisory Panel; Self; AstraZeneca, Gilead Sciences, Inc. Consultant; Self; Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Janssen Scientific Affairs, LLC., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Sanofi. Funding Sanofi

Efficacy and Safety of iGlarLixi, Fixed-Ratio Combination of Insulin Glargine and Lixisenatide, Compared with Basal-Bolus Regimen in Patients with Type2 Diabetes: Propensity Score Matched Analysis.

IntroductionBasal-bolus (BB) regimens are generally used to intensify basal insulin therapy in patients with type 2 diabetes (T2D) not meeting glycemic targets. However, drawbacks include multiple injection burden and risk of weight gain and hypoglycemia. A once-daily titratable fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide (iGlarLixi) may provide a simple, well-tolerated, and efficacious alternative. We compared these treatments in a post hoc propensity score matched analysis using randomized trial data.MethodsFrom the LixiLan-L study, 195 patients who had been randomized to iGlarLixi were matched for age, sex, race, T2D duration, baseline body mass index, glycated hemoglobin (HbA1c), fasting plasma glucose, insulin dose, and metformin use to 195 patients who had been randomized to a BB regimen in the GetGoal Duo-2 trial.ResultsAt study end, estimated treatment differences for reduction in HbA1c and weight change, and ratio of hypoglycemia events per patient-year (BB vs iGlarLixi) were − 0.28% (standard error 0.08, P = 0.0002), − 1.32 kg (standard error 0.30, P < 0.0001), and 2.85 (P < 0.0001), respectively, all favoring iGlarLixi over BB. Also, proportions of patients reaching individual and composite goals (HbA1c < 7% [< 53 mmol/mol], no weight gain, and no hypoglycemia) were higher in the iGlarLixi compared with the BB treatment group. Gastrointestinal side effects were more common with iGlarLixi.ConclusionsIn patients with T2D inadequately controlled on basal insulin, iGlarLixi offers an effective alternative to BB regimen for reducing HbA1c, without increased risk of hypoglycemia and weight gain.Trial RegistrationClinicalTrials.gov: NCT02058160 (LixiLan-L trial); NCT01768559 (GetGoal Duo-2 trial).Plain Language SummaryPlain language summary available for this article.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-019-00735-7) contains supplementary material, which is available to authorized users.