Comparing a daily versus weekly titration algorithm in people with type 2 diabetes switching from basal insulin to iGlarLixi in the LixiLan ONE CAN randomized trial

Irene Hramiak, Hertzel C Gerstein, Lawrence A Leiter, Jean-François Yale, Harpreet S Bajaj, John Stewart, Marie-Josée Toutounji, Stewart B Harris, Irene Hramiak, Hertzel C Gerstein, Lawrence A Leiter, Jean-François Yale, Harpreet S Bajaj, John Stewart, Marie-Josée Toutounji, Stewart B Harris

Abstract

Aim: To compare the efficacy and safety of a simple daily titration algorithm compared with a weekly dose adjustment of iGlarLixi in people with type 2 diabetes.

Materials and methods: LixiLan ONE CAN (NCT03767543), a randomized, 26-week, open-label, multicentre phase 3 trial conducted in Canada, involved 265 people with type 2 diabetes and an HbA1c of ≥7.5% to ≤ 10.5% or less (≥58 to ≤91 mmol/mol) on basal insulin for 6 months or longer. Participants were randomized 1:1 with instructions to self-titrate iGlarLixi daily (1 unit/day) or once weekly (2 or 4 units/week) to a common target fasting plasma glucose of 4.4 to 5.6 mmol/L (79 to 101 mg/dl). The primary objective was to show non-inferiority of the daily versus weekly titration algorithm.

Results: At 26 weeks, daily titration of iGlarLixi was not inferior to a weekly titration for both the prespecified primary endpoint of change in HbA1c from baseline (least square [LS] mean change: -1.24% vs. -0.92%, respectively; LS mean difference: 0.32%; 95% CI [0.07, 0.57]; P < .0001) and for the secondary endpoint of change in weight from baseline (LS mean change: -0.22 vs. +0.81 kg, respectively; LS mean difference: 1.03 kg; 95% CI [0.01, 2.06]; P < .0001). Indeed, for both the primary and secondary outcome, the daily titration of iGlarLixi was superior. There were no statistically significant differences in hypoglycaemia incidence between the two titration strategies during the 26-week study.

Conclusion: A daily titration algorithm for switching basal insulin to iGlarLixi was shown to be non-inferior and superior for glycaemic control and weight compared with weekly titration.

Keywords: GLP-1 analogues; basal insulin; glycaemic control; phase III; randomized trial; type 2 diabetes.

Conflict of interest statement

IH reports grants, personal fees and non‐financial support from AstraZeneca/Bristol‐Myers Squibb, personal fees from Bausch Health, personal fees from Boehringer Ingelheim/Eli Lilly (BI‐LILLY joint venture), personal fees and non‐financial support from Dexcom, grants and personal fees from Eli Lilly & Co, grants, personal fees and non‐financial support from GlaxoSmithKline, personal fees and non‐financial support from Insulet Corp, grants, personal fees and non‐financial support from Medtronic, grants, personal fees and non‐financial support from Novo Nordisk, grants, personal fees and non‐financial support from Sanofi‐Aventis, personal fees from Bayer Inc., outside the submitted work. HCG holds the McMaster‐Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly, AstraZeneca, Merck, Novo Nordisk and Sanofi; honoraria for speaking from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi, DKSH and Zuellig; and consulting fees from Abbott, Covance, Eli Lilly, Novo Nordisk, Sanofi, Pfizer and Kowa. LAL reports research support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Lexicon, Novo Nordisk and Sanofi; participation in Advisory Boards for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Pfizer and Sanofi; and honoraria for speaking from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Sanofi and Servier. J‐FY reports research grants from Sanofi, Novo Nordisk and Bayer Inc.; and honoraria for speaking and participation in Advisory Boards from Merck & Co Inc., AstraZeneca, Janssen, Eli Lilly, Sanofi, Novo Nordisk, Boehringer Ingelheim, Abbott, Medtronic, Dexcom and Bayer Inc. HSB reports research support from Amgen Inc., AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead Science, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co. Inc., Novo Nordisk, Sanofi and Tricida Inc. He also reports honoraria for speaking from Eli Lilly and Novo Nordisk. JS and M‐JT are employees of Sanofi and may hold shares or stock options in the company. SBH reports consulting fees, honoraria for speaking, participation on a Data Safety Monitoring or Advisory Board for Abbott, AstraZeneca, Bayer Inc., Eli Lilly, HLS Therapeutics, Janssen, Novo Nordisk and Sanofi. He also reports research grants from Abbott, Applied Therapeutics Inc., AstraZeneca, Canadian Institutes for Health Research, Juvenile Diabetes Research Foundation, Novo Nordisk, Sanofi and The Lawson Foundation.

© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Study participants flowchart and disposition. COVID‐19, coronavirus disease 2019. † One participant was entered as a duplicate and was not included in any summary. ‡ No participants stopped the study for an event related to COVID‐19. § No participants stopped the study for other reasons related to COVID‐19
FIGURE 2
FIGURE 2
A, Insulin glargine dosage per titration group (safety population), and B, Mean fasting plasma glucose (FPG) levels over the 26‐week study period (mITT population). Presentation of the 95% confidence intervals is used for descriptive purposes only

References

    1. Blonde L, Aschner P, Bailey C, et al. Gaps and barriers in the control of blood glucose in people with type 2 diabetes. Diabetes Vasc Dis Res. 2017;14(3):172‐183.
    1. Russell‐Jones D, Pouwer F, Khunti K. Identification of barriers to insulin therapy and approaches to overcoming them. Diabetes Obes Metab. 2018;20(3):488‐496.
    1. Leiter LA, Berard L, Bowering CK, et al. Type 2 diabetes mellitus management in Canada: is it improving? Can J Diabetes. 2013;37(2):82‐89.
    1. Leiter LA, Cheng AYY, Ekoé JM, et al. Glycated hemoglobin level goal achievement in adults with type 2 diabetes in Canada: still room for improvement. Can J Diabetes. 2019;43(6):384‐391.
    1. American Diabetes Association . 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes‐2021. Diabetes Care. 2021;44(Suppl 1):S111‐S124.
    1. Diabetes Canada Clinical Practice Guidelines Expert Committee , Lipscombe L, Butalia S, et al. Pharmacologic glycemic management of type 2 diabetes in adults: 2020 update. Can J Diabetes. 2020;44(7):575‐591.
    1. Blonde L, Anderson JE, Chava P, Dendy JA. Rationale for a titratable fixed‐ratio co‐formulation of a basal insulin analog and a glucagon‐like peptide 1 receptor agonist in patients with type 2 diabetes. Curr Med Res Opin. 2019;35(5):793‐804.
    1. Maiorino MI, Chiodini P, Bellastella G, Capuano A, Esposito K, Giugliano D. Insulin and glucagon‐like peptide 1 receptor agonist combination therapy in type 2 diabetes: a systematic review and meta‐analysis of randomized controlled trials. Diabetes Care. 2017;40(4):614‐624.
    1. Aroda VR, Rosenstock J, Wysham C, et al. Efficacy and safety of LixiLan, a titratable fixed‐ratio combination of insulin glargine plus Lixisenatide in type 2 diabetes inadequately controlled on basal insulin and metformin: the LixiLan‐L randomized trial [published correction appears in Diabetes Care. 2017 Jun;40(6):809]. Diabetes Care. 2016;39(11):1972‐1980.
    1. Rosenstock J, Aronson R, Grunberger G, et al. Benefits of LixiLan, a titratable fixed‐ratio combination of insulin glargine plus Lixisenatide, versus insulin glargine and Lixisenatide Monocomponents in type 2 diabetes inadequately controlled on oral agents: the LixiLan‐O randomized trial. Diabetes Care. 2016;39(11):2026‐2035.
    1. Gough SC, Bode B, Woo V, et al. Efficacy and safety of a fixed‐ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open‐label, randomised, 26‐week, treat‐to‐target trial in insulin‐naive patients with type 2 diabetes. Lancet Diabetes Endocrinol. 2014;2(11):885‐893.
    1. Buse JB, Vilsbøll T, Thurman J, et al. Contribution of liraglutide in the fixed‐ratio combination of insulin degludec and liraglutide (IDegLira). Diabetes Care. 2014;37(11):2926‐2933.
    1. Perreault L, Rodbard H, Valentine V, Johnson E. Optimizing fixed‐ratio combination therapy in type 2 diabetes. Adv Ther. 2019;36(2):265‐277.
    1. Haluzík M, Flekač M, Lengyel C, et al. Expert opinion on the therapeutic use of the fixed‐ratio combination of insulin glargine 100 U/mL and Lixisenatide: a central/eastern European perspective. Diabetes Ther. 2020;11(4):1029‐1043.
    1. Gerstein HC, Yale JF, Harris SB, Issa M, Stewart JA, Dempsey E. A randomized trial of adding insulin glargine vs avoidance of insulin in people with type 2 diabetes on either no oral glucose‐lowering agents or submaximal doses of metformin and/or sulphonylureas. The Canadian INSIGHT (implementing new strategies with insulin glargine for Hyperglycaemia treatment) study. Diabetic Med. 2006;23(7):736‐742.
    1. Yale JF, Berard L, Groleau M, Javadi P, Stewart J, Harris SB. TITRATION: a randomized study to assess 2 treatment algorithms with new insulin glargine 300 units/mL. Can J Diabetes. 2017;41(5):478‐484.
    1. American Diabetes Association . 6. Glycemic targets: standards of medical care in diabetes‐2021. Diabetes Care. 2021;44(Suppl 1):S73‐S84.
    1. Khunti K, Giorgino F, Berard L, Mauricio D, Harris SB. The importance of the initial period of basal insulin titration in people with diabetes. Diabetes Obes Metab. 2020;22(5):722‐733.
    1. Kuritzky L, Reid TS, Wysham CH. Practical guidance on effective basal insulin titration for primary care providers. Clin Diabetes. 2019;37(4):368‐376.
    1. Yale JF, Roborel de Climens A, Aggarwal N, et al. Ease of using iGlarLixi pen after insulin glargine Gla‐100: results from patient and healthcare provider questionnaires from the one CAN pen sub‐study. Poster presented at: 14th international conference on advanced technologies & treatments for diabetes, June 2‐5, 2021. Diabetes Technol Ther. 2021;23(S2):A‐1‐A‐206.

Source: PubMed

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