Dataset Information

Anti-Insulin Antibodies and Adverse Events with Biosimilar Insulin Lispro Compared with Humalog Insulin Lispro in People with Diabetes.

ABSTRACT: BACKGROUND:SAR342434 (SAR-Lis) is a biosimilar (follow-on) of insulin lispro (Humalog®; Ly-Lis). Two randomized, controlled, open-label, parallel-group, phase 3 studies were conducted to compare the efficacy and safety of SAR-Lis and Ly-Lis, both in combination with insulin glargine (Lantus®). SORELLA 1 was a 12-month study in 507 people with type 1 diabetes mellitus (T1DM); SORELLA 2 was a 6-month study in 505 people with type 2 diabetes mellitus (T2DM). In this study, the impact of anti-insulin antibodies (AIA) to SAR-Lis and Ly-Lis on safety and glycemic control is reported. METHODS:AIA were measured regularly throughout both studies at a centralized laboratory blinded to treatment groups using a drug-specific AIA assay. The AIA status (positive or negative), AIA titers, and cross-reactivity to human insulin, insulin glargine, and insulin glargine metabolite M1 were analyzed. The potential effect of AIA on safety, particularly as related to hypersensitivity reactions, hypoglycemia, and treatment-emergent adverse events, as well as on glycemic control (HbA1c, insulin dose), was evaluated. RESULTS:AIA positive status at baseline was similar for the two insulins, but higher in T1DM than in T2DM. In both studies, the percentage of people newly developing AIA in the two treatment groups, or having a ?4-fold increase in AIA titers, did not differ. No relationship was observed between maximum individual AIA titers and change in HbA1c or insulin dose, hypoglycemia, or hypersensitivity reactions or between efficacy/safety measures and subgroups by presence or absence of treatment-emergent AIA. Hypersensitivity events and events adjudicated as allergic reactions were few and did not differ between the two groups. CONCLUSION:Insulin lispro SAR342434 and the originator insulin lispro had a similar immunogenicity profile in people with T1DM or T2DM.

SUBMITTER: Home P

PROVIDER: S-EPMC5771536 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Anti-Insulin Antibodies and Adverse Events with Biosimilar Insulin Lispro Compared with Humalog Insulin Lispro in People with Diabetes.

Home Philip P Derwahl Karl-Michael KM Ziemen Monika M Wernicke-Panten Karin K Pierre Suzanne S Kirchhein Yvonne Y Garg Satish K SK

Diabetes technology & therapeutics 20180201 2

<h4>Background</h4>SAR342434 (SAR-Lis) is a biosimilar (follow-on) of insulin lispro (Humalog<sup>®</sup>; Ly-Lis). Two randomized, controlled, open-label, parallel-group, phase 3 studies were conducted to compare the efficacy and safety of SAR-Lis and Ly-Lis, both in combination with insulin glargine (Lantus<sup>®</sup>). SORELLA 1 was a 12-month study in 507 people with type 1 diabetes mellitus (T1DM); SORELLA 2 was a 6-month study in 505 people with type 2 diabetes mellitus (T2DM). In this st ...[more]

PMID: 29355435

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Project description:IntroductionThe aim of this study was to evaluate the efficacy and safety of ultra-rapid lispro (URLi) versus lispro in a subgroup analysis of Japanese adults with type 2 diabetes mellitus (T2DM) from the phase 3 PRONTO-T2D trial.MethodsAfter an 8-week lead-in period during which patients transitioned to insulin lispro 3 times a day before main meals in association with basal insulin (glargine or degludec), the patients were randomized to 26 weeks of double-blind URLi or lispro injected immediately prior to meals. The primary endpoint was change in hemoglobin A1c (HbA1c) from baseline to week 26 between URLi and lispro. The multiplicity-adjusted objectives were 1- and 2-h postprandial glucose (PPG) excursions after a test meal and change in HbA1c from baseline to week 26 in the URLi and lispro groups.ResultsResults were obtained from prespecified exploratory analyses of 26-week data in Japanese patients randomized to receive URLi (n = 47) or lispro (n = 46). Mean baseline HbA1c levels significantly improved during the lead-in period to a baseline value of 7.50% and 7.60% in patients subsequently randomized to the URLi and lispro treatment groups, respectively. At week 26, the least squares mean (LSM) difference in HbAc1 between the URLi and lispro groups was 0.13% (95% confidence interval [CI] - 0.12 to 0.39) (1.4 mmol/mol, 95% CI - 1.3 to 4.2). Although there were no significant differences in PPG excursions at any time-point, numerically smaller PPG excursions were consistently observed from 30 min to 3 h during the mixed-meal tolerance test in patients on URLi compared to those on lispro. LSM differences in PPG excursions at week 26 were - 10.5 mg/dL (95% CI - 32.7 to 11.7) (- 0.58 mmol/L, 95% CI - 1.82 to 0.65) at 1 h and - 14.9 mg/dL (95% CI - 40.3 to 10.5) (- 0.83 mmol/L, 95% CI - 2.24 to 0.58) at 2 h. There were no significant differences between treatments in rates of severe/overall hypoglycemia or incidence of treatment-emergent adverse events.ConclusionsURLi administered as prandial insulin in combination with basal insulin provides effective glycemic control when administered immediately before a meal in Japanese patients with T2DM. URLi was well tolerated in this population.Trial registrationClinicalTrials.gov, NCT03214380.

Project description:IntroductionWe evaluated the efficacy and safety of ultra-rapid lispro (URLi) in comparison to lispro in a subgroup analysis of Japanese adults with type 1 diabetes mellitus from the phase 3 PRONTO-T1D trial.MethodsAfter an 8-week lead-in to optimize basal insulin treatment, patients were randomized to 52-week double-blind mealtime URLi or lispro, or 26-week open-label postmeal URLi. The primary endpoint was change in hemoglobin A1c (HbA1c) from baseline (week 0) to week 26 between mealtime URLi and lispro. The multiplicity adjusted objectives were 1- and 2-h postprandial glucose (PPG) excursions after a meal test between mealtime URLi and lispro, and change in HbA1c from baseline to week 26 between postmeal URLi and mealtime lispro.ResultsThis manuscript presents pre-specified exploratory analyses of 26-week data from Japanese patients randomized to double-blind URLi (n = 62) or lispro (n = 59), or open-label URLi (n = 46). Mean baseline HbA1c levels were 7.52% for mealtime URLi, 7.44% for lispro, and 7.51% for postmeal URLi at randomization. At week 26, the least squares mean (LSM) difference compared to lispro was 0.04% (95% confidence interval [CI] - 0.14 to 0.22) for mealtime URLi, and 0.16% (95% CI - 0.04 to 0.35) for postmeal URLi. In comparison to lispro, mealtime URLi resulted in statistically significantly lower 1- and 2-h PPG excursions during the mixed-meal tolerance test. LSM differences were - 40.5 mg/dL, 95% CI - 59.5 to 21.4 (- 2.25 mmol/L, 95% CI - 3.3 to - 1.2) for 1-h PPG excursions and - 51.7 mg/dL, 95% CI - 81.7 to - 21.8 (- 2.87 mmol/L, 95% CI - 4.5 to - 1.2) for 2-h PPG excursions at week 26. There were no significant treatment differences in rates of severe/overall hypoglycemia, or incidence of treatment-emergent adverse events.ConclusionsMealtime and postmeal URLi provide effective and comparable glycemic control in Japanese patients. Mealtime URLi demonstrated more effective PPG control compared to lispro.Trial registrationClinicalTrials.gov, NCT03214367.

Dataset Information

Anti-Insulin Antibodies and Adverse Events with Biosimilar Insulin Lispro Compared with Humalog Insulin Lispro in People with Diabetes.

Publications

Anti-Insulin Antibodies and Adverse Events with Biosimilar Insulin Lispro Compared with Humalog Insulin Lispro in People with Diabetes.

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