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Impact of dose capping in insulin glargine/lixisenatide fixed-ratio combination trials in patients with type 2 diabetes.
Curr Med Res Opin. 2019 06; 35(6):1081-1089.CM

Abstract

OBJECTIVE

The LixiLan clinical trials of insulin glargine (iGlar)/lixisenatide fixed-ratio combination (iGlarLixi) investigated the safety and efficacy of iGlarLixi versus iGlar: LixiLan-O (NCT02058147) in patients with type 2 diabetes (T2D) inadequately controlled on oral antidiabetes drugs (OADs) and LixiLan-L (NCT02058160) in patients with T2D inadequately controlled on basal insulin ± OADs. In these two trials, both iGlar and iGlarLixi were titrated to a maximum (capped) dose of 60 units. We evaluated whether this may have affected the reported glycemic efficacy of iGlar, and the glycemic differences observed between treatment with iGlarLixi and iGlar.

METHODS

The efficacy of iGlar under uncapped conditions was simulated in a two-step approach. First, a model characterizing the relationship between iGlar dose and fasting self-measured plasma glucose (f-SMPG) was developed. Then, the relationship between glycated hemoglobin A1c (A1C) and f-SMPG was established to translate simulated f-SMPG responses to A1C responses.

RESULTS

Most patients achieved stable f-SMPG at ∼60 units/day, with no further reduction with increasing insulin dose. In comparisons of observed/capped and simulated/uncapped changes in mean A1C from baseline to Week 30, iGlarLixi consistently demonstrated treatment benefit compared with iGlar. Uncapping resulted in a slightly higher mean iGlar dose in both LixiLan-O (+0.72 units) and LixiLan-L (+2.1 units), without marked impact on f-SMPG or A1C change from baseline.

CONCLUSION

Uncapping the iGlar dose in LixiLan-O and LixiLan-L would not have led to significant improvements in mean A1C reduction in the iGlar arm, supporting the conclusion that iGlarLixi provides additional, clinically relevant glycemic control versus iGlar alone.

Authors+Show Affiliations

a Sanofi Germany , Frankfurt , Germany.b Sanofi US, Inc. , Bridgewater , NJ , USA.b Sanofi US, Inc. , Bridgewater , NJ , USA.a Sanofi Germany , Frankfurt , Germany.c Sanofi Paris , Paris , France.d National Research Institute , Los Angeles , CA , USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30550345

Citation

Schmider, Wolfgang, et al. "Impact of Dose Capping in Insulin Glargine/lixisenatide Fixed-ratio Combination Trials in Patients With Type 2 Diabetes." Current Medical Research and Opinion, vol. 35, no. 6, 2019, pp. 1081-1089.
Schmider W, Belder R, Lee M, et al. Impact of dose capping in insulin glargine/lixisenatide fixed-ratio combination trials in patients with type 2 diabetes. Curr Med Res Opin. 2019;35(6):1081-1089.
Schmider, W., Belder, R., Lee, M., Niemoeller, E., Souhami, E., & Frias, J. P. (2019). Impact of dose capping in insulin glargine/lixisenatide fixed-ratio combination trials in patients with type 2 diabetes. Current Medical Research and Opinion, 35(6), 1081-1089. https://doi.org/10.1080/03007995.2018.1558852
Schmider W, et al. Impact of Dose Capping in Insulin Glargine/lixisenatide Fixed-ratio Combination Trials in Patients With Type 2 Diabetes. Curr Med Res Opin. 2019;35(6):1081-1089. PubMed PMID: 30550345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of dose capping in insulin glargine/lixisenatide fixed-ratio combination trials in patients with type 2 diabetes. AU - Schmider,Wolfgang, AU - Belder,Rene, AU - Lee,Michelle, AU - Niemoeller,Elisabeth, AU - Souhami,Elisabeth, AU - Frias,Juan P, Y1 - 2019/01/11/ PY - 2018/12/15/pubmed PY - 2020/4/15/medline PY - 2018/12/15/entrez KW - Lixisenatide KW - fixed-ratio combination insulin/GLP-1 receptor agonist KW - iGlarLixi KW - insulin glargine SP - 1081 EP - 1089 JF - Current medical research and opinion JO - Curr Med Res Opin VL - 35 IS - 6 N2 - OBJECTIVE: The LixiLan clinical trials of insulin glargine (iGlar)/lixisenatide fixed-ratio combination (iGlarLixi) investigated the safety and efficacy of iGlarLixi versus iGlar: LixiLan-O (NCT02058147) in patients with type 2 diabetes (T2D) inadequately controlled on oral antidiabetes drugs (OADs) and LixiLan-L (NCT02058160) in patients with T2D inadequately controlled on basal insulin ± OADs. In these two trials, both iGlar and iGlarLixi were titrated to a maximum (capped) dose of 60 units. We evaluated whether this may have affected the reported glycemic efficacy of iGlar, and the glycemic differences observed between treatment with iGlarLixi and iGlar. METHODS: The efficacy of iGlar under uncapped conditions was simulated in a two-step approach. First, a model characterizing the relationship between iGlar dose and fasting self-measured plasma glucose (f-SMPG) was developed. Then, the relationship between glycated hemoglobin A1c (A1C) and f-SMPG was established to translate simulated f-SMPG responses to A1C responses. RESULTS: Most patients achieved stable f-SMPG at ∼60 units/day, with no further reduction with increasing insulin dose. In comparisons of observed/capped and simulated/uncapped changes in mean A1C from baseline to Week 30, iGlarLixi consistently demonstrated treatment benefit compared with iGlar. Uncapping resulted in a slightly higher mean iGlar dose in both LixiLan-O (+0.72 units) and LixiLan-L (+2.1 units), without marked impact on f-SMPG or A1C change from baseline. CONCLUSION: Uncapping the iGlar dose in LixiLan-O and LixiLan-L would not have led to significant improvements in mean A1C reduction in the iGlar arm, supporting the conclusion that iGlarLixi provides additional, clinically relevant glycemic control versus iGlar alone. SN - 1473-4877 UR - https://www.unboundmedicine.com/medline/citation/30550345/Impact_of_dose_capping_in_insulin_glargine/lixisenatide_fixed_ratio_combination_trials_in_patients_with_type_2_diabetes_ L2 - http://www.tandfonline.com/doi/full/10.1080/03007995.2018.1558852 DB - PRIME DP - Unbound Medicine ER -