Clinical Characteristics and Glycemic Outcomes of Patients with Type 2 Diabetes Requiring Maximum Dose Insulin Glargine/Lixisenatide Fixed-Ratio Combination or Insulin Glargine in the LixiLan-L Trial

Lawrence Blonde, Timothy S Bailey, Jason Chao, Terry A Dex, Juan Pablo Frias, Luigi F Meneghini, Michelle Roberts, Vanita R Aroda, Lawrence Blonde, Timothy S Bailey, Jason Chao, Terry A Dex, Juan Pablo Frias, Luigi F Meneghini, Michelle Roberts, Vanita R Aroda

Abstract

Introduction: iGlarLixi is a titratable, fixed-ratio combination of insulin glargine (iGlar, 100 units/ml) and the glucagon-like peptide-1 receptor agonist lixisenatide for the treatment of patients with type 2 diabetes. This post hoc analysis of the phase 3 LixiLan-L trial (NCT02058160) investigated baseline characteristics, glycemic control, and safety outcomes in participants who received the study-specified maximum dose (60 units/day) of iGlarLixi or iGlar vs. those who received < 60 units/day.

Methods: Outcomes were compared for participants receiving 60 or < 60 units/day at week 30. Endpoints analyzed included change in A1C, fasting plasma glucose (FPG), 2-h postprandial glucose (2-h PPG), body weight, proportion of participants achieving A1C < 7.0%, proportion of participants receiving rescue therapy, documented symptomatic hypoglycemia, and gastrointestinal adverse event (GI AE) incidence.

Results: By week 30, 27% (iGlarLixi) and 31% (iGlar) of participants received the maximum dose. Participants on 60 vs. < 60 units/day were younger and had higher body weight, body mass index (BMI), FPG, and baseline insulin dose. In both dose groups, A1C change from baseline was significantly greater with iGlarLixi vs. iGlar, and more participants treated with iGlarLixi vs. iGlar achieved A1C < 7.0%. No significant differences were observed in change from baseline for A1C, FPG, 2-h PPG, or GI AE incidence between insulin dose groups, regardless of treatment. In both treatment arms, incidence of symptomatic hypoglycemia was lower in participants receiving 60 units/day vs. those receiving < 60 units/day. Participants treated with iGlarLixi (< 60 or 60 units/day) had modest weight loss over 30 weeks vs. an increase in weight compared with iGlar.

Conclusions: Maximum doses of iGlarLixi were required in participants with a more insulin-resistant clinical phenotype (younger, higher BMI, FPG, and insulin doses). Benefits were observed with iGlarLixi vs. iGlar, even at 60 units/day, with more participants achieving glycemic goals, no increase in symptomatic hypoglycemia, and a modest reduction in body weight.

Funding: Sanofi US, Inc.

Keywords: GLP-1 RA; Glycemic control; Hypoglycemia; Insulin dose; Type 2 diabetes.

Figures

Fig. 1
Fig. 1
Percentage of patients using a glycated hemoglobin < 7.0% (< 53 mmol/mol) at week 30 and b glycated hemoglobin < 7.0% (< 53 mmol/mol) with no body weight gain at week 30 and with no hypoglycemia during the study. Analyses based on safety population. A1C glycated hemoglobin, iGlar insulin glargine 100 units/ml, iGlarLixi fixed-ratio combination of iGlar and lixisenatide
Fig. 2
Fig. 2
a Weight change from baseline to week 30 and b incidence of documented symptomatic hypoglycemia for patients receiving doses of < 60 units/day or 60 units/day. Analyses based on safety population. iGlar insulin glargine 100 units/ml, iGlarLixi fixed-ratio combination of iGlar and lixisenatide

References

    1. Khunti K, Wolden ML, Thorsted BL, Andersen M, Davies MJ. Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes Care. 2013;36:3411–3417. doi: 10.2337/dc13-0331.
    1. Khunti K, Nikolajsen A, Thorsted BL, Andersen M, Davies MJ, Paul SK. Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin. Diabetes Obes Metab. 2016;18:401–409. doi: 10.1111/dom.12626.
    1. Calvert MJ, McManus RJ, Freemantle N. Management of type 2 diabetes with multiple oral hypoglycaemic agents or insulin in primary care: retrospective cohort study. Br J Gen Pract. 2007;57:455–460.
    1. Nichols GA, Koo YH, Shah SN. Delay of insulin addition to oral combination therapy despite inadequate glycemic control: delay of insulin therapy. J Gen Intern Med. 2007;22:453–458. doi: 10.1007/s11606-007-0139-y.
    1. DeFronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773–795. doi: 10.2337/db09-9028.
    1. Balena R, Hensley IE, Miller S, Barnett AH. Combination therapy with GLP-1 receptor agonists and basal insulin: a systematic review of the literature. Diabetes Obes Metab. 2013;15:485–502. doi: 10.1111/dom.12025.
    1. Vora J. Combining incretin-based therapies with insulin: realizing the potential in type 2 diabetes. Diabetes Care. 2013;36(Suppl 2):S226–S232. doi: 10.2337/dcS13-2036.
    1. Horowitz M, Rayner CK, Jones KL. Mechanisms and clinical efficacy of lixisenatide for the management of type 2 diabetes. Adv Ther. 2013;30:81–101. doi: 10.1007/s12325-013-0009-4.
    1. Soliqua®. Prescribing information. . Accessed March 2019.
    1. Suliqua®. Summary of product characteristics. . Accessed June 2018.
    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. Diabetes Care. 2016;39:1972–1980. doi: 10.2337/dc16-1495.
    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;39:2026–2035. doi: 10.2337/dc16-0917.
    1. McAdam-Marx C, Yu J, Bouchard J, Aagren M, Brixner DI. Comparison of daily insulin dose and other antidiabetic medications usage for type 2 diabetes patients treated with an analog basal insulin. Curr Med Res Opin. 2010;26:191–201. doi: 10.1185/03007990903432470.
    1. Borah BJ, Darkow T, Bouchard J, Aagren M, Forma F, Alemayehu B. A comparison of insulin use, glycemic control, and health care costs with insulin detemir and insulin glargine in insulin-naive patients with type 2 diabetes. Clin Ther. 2009;31:623–631. doi: 10.1016/j.clinthera.2009.03.005.
    1. Umpierrez GE, Skolnik N, Dex T, Traylor L, Chao J, Shaefer C. When basal insulin is not enough: a dose-response relationship between insulin glargine 100 units/mL and glycaemic control. Diabetes Obes Metab. 2019 doi: 10.1111/dom.13653.
    1. American Diabetes Association Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019;42(Suppl 1):S1–S193.
    1. Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Care. 2018;41:2669–2701. doi: 10.2337/dci18-0033.
    1. Shaefer C, Traylor L, Gao L, Dex T, Sepe P, Skolnik N. Exploratory study of a dose–response curve for basal insulin. Diabetes. 2015;64(Suppl 1): Abstract 253.
    1. LaSalle JR, Berria R. Insulin therapy in type 2 diabetes mellitus: a practical approach for primary care physicians and other health care professionals. J Am Osteopath Assoc. 2013;113:152–162.
    1. Reid T, Gao L, Gill J, et al. How much is too much? Outcomes in patients using high-dose insulin glargine. Int J Clin Pract. 2016;70:56–65. doi: 10.1111/ijcp.12747.
    1. Riddle MC, Aronson R, Home P, et al. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L) Diabetes Care. 2013;36:2489–2496. doi: 10.2337/dc12-2454.
    1. Rosenstock J, Diamant M, Aroda VR, et al. Efficacy and safety of LixiLan, a titratable fixed-ratio combination of lixisenatide and insulin glargine, versus insulin glargine in type 2 diabetes inadequately controlled on metformin monotherapy: the LixiLan proof-of-concept randomized trial. Diabetes Care. 2016;39:1579–1586. doi: 10.2337/dc16-0046.

Source: PubMed

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