Dataset Information

Lilly Insulin Glargine Versus Lantus^® in Insulin-Naive and Insulin-Treated Adults with Type 2 Diabetes: A Randomized, Controlled Trial (ELEMENT 5).

ABSTRACT:

Introduction

This study compared the efficacy and safety of similar U-100 insulin glargine products, namely, Lilly insulin glargine (LY IGlar; Basaglar^®) and the reference insulin glargine product (IGlar; Lantus^®), used once daily in combination with oral antihyperglycemic medications (OAMs) in adults with type 2 diabetes (T2D).

Methods

ELEMENT 5 was a phase III, randomized, multinational, open-label, treat-to-target, 24-week trial. Participants were insulin naïve (glycated hemoglobin [HbA1c] ≥ 7.0% to ≤ 11.0%) or on basal insulin (IGlar, neutral protamine Hagedorn or insulin detemir; HbA1c ≤ 11.0%) and taking ≥ 2 OAMs. The primary objective was to show that LY IGlar is noninferior to IGlar in terms of HbA1c reduction (0.4% noninferiority margin).

Results

The study population (N = 493) was predominantly Asian (48%) or White (46%), with similar baseline characteristics between arms (P > 0.05). At 24 weeks, LY IGlar was noninferior to IGlar in terms of change in HbA1c level from baseline (- 1.25 vs. - 1.22%, respectively; least squares mean difference - 0.04%; 95% confidence interval - 0.22%, 0.15%). Other 24-week efficacy and safety results were also similar between treatments (P > 0.05), including insulin dose; percentage of patients having HbA1c of < 7% and ≤ 6.5%; overall rate and incidence of total, nocturnal, and severe hypoglycemia; adverse events; insulin antibody response; and weight gain. Daily mean 7-point self-monitored blood glucose reduction was similar between treatments at 24 weeks, with no differences at any time point except premorning-meal (fasting) blood glucose (LY IGlar - 2.37 mmol/L; IGlar - 2.69 mmol/L; P = 0.007).

Conclusion

Overall, LY IGlar and IGlar combined with OAMs provided similar glucose control and safety findings in this T2D population, which included a greater proportion of Asian patients and had broader background basal insulin experience than a previously studied T2D population.

Trial registration

ClinicalTrials.gov identifier, NCT02302716.

Funding

Eli Lilly and Company and Boehringer Ingelheim. Plain language summary available for this article.

SUBMITTER: Pollom RK

PROVIDER: S-EPMC6349279 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectivesLilly insulin glargine (LY IGlar; Basaglar®) and the reference insulin glargine product (IGlar; Lantus®) are basal insulin glargine analogs with identical amino acid sequence and similar pharmacological profiles. ELEMENT 5, a Phase 3, prospective, randomized, multinational, two-arm, active-controlled, open-label, parallel-design study in type 2 diabetes mellitus (T2DM) patients (N = 493) showed similar efficacy and safety profiles with LY IGlar and IGlar. This study reports results from India (N = 100) and East Asia (N = 134) subpopulations.MethodsPatients from India and East Asia (Korea and Taiwan) with T2DM who were insulin naïve (glycated hemoglobin (HbA1c) ≥ 7.0% and ≤ 11.0%) or on basal insulin (HbA1c ≤ 11.0%) were randomized to receive LY IGlar or IGlar along with oral antihyperglycemic medications (OAMs) for 24 weeks. Patients were instructed to self-titrate from the starting dose by 1 unit/day until fasting blood glucose (FBG) ≤ 5.6 mmol/L (100 mg/dL) was achieved. The key outcome was HbA1c change from baseline to Week 24.ResultsWithin-group least-squares mean (LSM) decrease (baseline to Week 24) in HbA1c was similar between treatments. The upper limit of confidence interval (CI) for treatment difference was below the defined 0.4% noninferiority margin in India (LY IGlar: - 0.83%; IGlar: - 0.62%; difference [95% CI] - 0.21 [- 0.70, 0.28]) and East Asia (LY IGlar: - 1.28%; IGlar: - 1.26%; difference [95% CI] - 0.02 [- 0.34, 0.30]) subpopulations. Results of other efficacy and safety endpoints at Week 24 were similar between treatments in both subpopulations. LSM self-monitored FBG levels were similar between treatments at all visits in both subpopulations except at Week 24 in the India subpopulation (LY IGlar: 5.65 [0.10] mmol/L or 101.8 [1.86] mg/dL; IGlar: 5.18 [0.10] mmol/L or 93.3 [1.75] mg/dL; p = 0.002).ConclusionEfficacy and safety profiles of LY IGlar and IGlar, in combination with OAMs, were similar in India and East Asia subpopulations. This was consistent with the ELEMENT 5 total population.Clinical trial registrationNCT02302716.

Project description:Insulin glargine is a long-acting insulin analog, which plays an important role in the treatment of diabetes mellitus. Biosimilar products of insulin glargine can provide patients with additional safe, high-quality, and potentially cost-effective options for treating diabetes. This article presents a randomized, double-blind, single-dose, two-treatment, four-period, replicate crossover, euglycemic clamp study which was designed to evaluate the PK and PD similarity between the recombinant insulin glargine developed by Wanbang (test) and Lantus® (reference) in healthy volunteers. Subjects received subcutaneous administration of the insulin glargine formulation (0.4 U/kg) on two occasions for the test and reference drug, respectively, and a 20% dextrose solution was infused at variable rate to clamp the blood glucose concentrations at 0.3 mmol/L below the subjects' fasting glucose for 24 h. Taking advantage of the improved sensitivity of the bioanalytical method applied and the solution of the matrix stability problem, the parent insulin glargine was determined in the vast majority of plasma samples using a fully validated UHPLC-MS/MS method. The PK characteristics of the parent insulin glargine were revealed for the first time: after subcutaneous injection, concentrations of the parent insulin glargine increased to a relative high level within 3 h, and then, a relatively flat concentration-time profile lasting for at least 12 h post-dose was observed. For the first time, the pharmacokinetic parameters of the parent insulin glargine were used as endpoints for similarity evaluation, which complied with the regulatory guidance better and made the similarity conclusion more powerful. The ratios of geometric means of all PK and PD endpoints were close to 100.00%. For the PK endpoints (AUC0-24h, Cmax, AUC0-12h, and AUC12-24h of the parent insulin glargine and its metabolite M1), the 90% confidence intervals of geometric mean ratios of test to reference were entirely contained within 80.00%-125.00%. For the PD endpoints [AUCGIR(0-24h), GIRmax, AUCGIR(0-12h), and AUCGIR(12-24h)], the 95% confidence intervals of geometric mean ratios of test to reference were entirely contained within 80.00%-125.00%. Based on the above mentioned results, it can be concluded that the PK and PD characteristics of the biosimilar drug developed by Wanbang are similar to those of Lantus.

Project description:BackgroundChronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal insulin treatment regimens for type 2 diabetes, but the long-acting insulin analogues seem beneficial. Several reviews have compared either insulin detemir or insulin glargine to NPH insulin, but research directly comparing both insulin analogues is limited.ObjectivesTo assess the effects of insulin detemir and insulin glargine compared with each other in the treatment of type 2 diabetes mellitus.Search strategyWe searched MEDLINE, EMBASE, The Cochrane Library, online registries of ongoing trials and abstract books. Date of last search was January 2011.Selection criteriaAll randomised controlled trials comparing insulin detemir with insulin glargine with a duration of 12 weeks or longer were included.Data collection and analysisTwo authors independently selected the studies and extracted the data. Pooling of studies by means of random-effects meta-analysis was performed.Main resultsThis review examined four trials lasting 24 to 52 weeks involving 2250 people randomised to either insulin detemir or glargine. Overall, risk of bias of the evaluated studies was high. Insulin glargine was dosed once-daily in the evening. Insulin detemir was initiated once-daily in the evening with the option of an additional dose in the morning in three studies and initiated twice-daily in one study. Of randomised patients 13.6% to 57.2% were injecting insulin detemir twice-daily at the end of trial.Glycaemic control, measured by glycosylated haemoglobin A1c (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not differ statistically significantly between treatment groups.The results showed no significant differences in overall, nocturnal and severe hypoglycaemia between treatment groups.Insulin detemir was associated with less weight gain. Treatment with insulin glargine resulted in a lower daily basal insulin dose and a lower number of injection site reactions.There was no significant difference in the variability of FPG or glucose values in 24-hour profiles between treatment groups. It was not possible to draw conclusions on quality of life, costs or mortality. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups.Authors' conclusionsOur analyses suggest that there is no clinically relevant difference in efficacy or safety between insulin detemir and insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control insulin detemir was often injected twice-daily in a higher dose but with less weight gain, while insulin glargine was injected once-daily, with somewhat fewer injection site reactions.

Dataset Information

Lilly Insulin Glargine Versus Lantus^® in Insulin-Naive and Insulin-Treated Adults with Type 2 Diabetes: A Randomized, Controlled Trial (ELEMENT 5).

Introduction

Methods

Results

Conclusion

Trial registration

Funding

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Lilly Insulin Glargine Versus Lantus® in Insulin-Naive and Insulin-Treated Adults with Type 2 Diabetes: A Randomized, Controlled Trial (ELEMENT 5).

Introduction

Methods

Results

Conclusion

Trial registration

Funding

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Lilly Insulin Glargine Versus Lantus^® in Insulin-Naive and Insulin-Treated Adults with Type 2 Diabetes: A Randomized, Controlled Trial (ELEMENT 5).