Use and effectiveness of a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) in a real-world population with type 2 diabetes: Results from a European, multicentre, retrospective chart review study

Hermione Price, Matthias Blüher, Rudolf Prager, Tra-Mi Phan, Brian L Thorsted, Bernd Schultes, EXTRA study group, Hermione Price, Matthias Blüher, Rudolf Prager, Tra-Mi Phan, Brian L Thorsted, Bernd Schultes, EXTRA study group

Abstract

Aims: To describe the real-world use and effectiveness of IDegLira, a fixed-ratio combination of the basal insulin degludec, and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide.

Materials and methods: This European, multicentre, retrospective chart review comprised adults (n = 611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data were available.

Results: Baseline regimens included non-injectable medications (19%), basal insulin (19%), GLP-1RA (10%), free combination therapy (insulin/GLP-1RA, 24%) and multiple daily-dose insulin injections (MDI, 28%), all ± oral antidiabetic drugs. After 6 months, significant glycated haemoglobin (HbA1c) reductions were observed in patients overall and in all subgroups (-10 mmol/mol [-0.9%] overall; P < .0001), and a significant reduction in mean body weight (-0.7 kg; P < .05) was observed in patients overall and in patients receiving MDI (-2.4 kg; P < .0001). The mean IDegLira dose was 22, 30 and 32 dose steps at initiation, and at 6 and 12 months follow-up, respectively. In total, only 67 patients reached the maximum 50 dose steps, with most coming from the free combination therapy (n = 31) or MDI (n = 15) baseline regimen groups. Hypoglycaemia rates were reduced by 82% (rate ratio 0.18; P < .0001) in the 6-month period after vs before IDegLira initiation. Overall, a total of 12 patients experienced 15 events in the 6 months after IDegLira initiation.

Conclusion: In real-world practice, after 6 months and at a moderate dose, IDegLira resulted in substantial reductions in HbA1c and body weight, with a reduced risk of hypoglycaemia.

Keywords: GLP-1 analogue; glycaemic control; insulin therapy; observational study; type 2 diabetes.

Conflict of interest statement

H.P. has received lecture fees from MSD, AstraZeneca, Lilly, Sanofi, Novo Nordisk and Boehringer Ingelheim, conference travel from Novo Nordisk, and received honoraria for advisory board or steering committee participation from Sanofi and Novo Nordisk. M.B. received honoraria for presentations and advisory board participations from Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, Lilly, Novartis, Novo Nordisk and Sanofi. R.P. has received honoraria for advisory board participation from Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novartis, Novo Nordisk and Sanofi. T‐M.P. was an employee of Novo Nordisk Region Europe A/S and owned stocks/shares in the company at the time of this study. B.L.T. is an employee and shareholder of Novo Nordisk A/S. B.S. has received honoraria for advisory board and speakers' bureau participation from Novo Nordisk, Sanofi, AstraZeneca, Lilly, Bayer and Boehringer Ingelheim, and for speakers' bureau participation from Sanofi, Lilly, MSD, Bayer and Boehringer Ingelheim.

© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Reasons for initiation of insulin degludec/liraglutide combination (IDegLira). Reasons were not mutually exclusive. Data based on full analysis set. AE, adverse event; GI, gastrointestinal
Figure 2
Figure 2
Change from baseline to 6 months in A, insulin degludec/liraglutide combination (IDegLira) dose; B, glycated haemoglobin (HbA1c) and C, body weight by baseline therapy subgroup. *P < .0001. Data based on effectiveness analysis set. Significance assessed using a two‐tailed paired t test. BL, baseline; F/U, follow‐up; GLP‐1RA, glucagon‐like peptide‐1 receptor agonist; MDI, multiple daily‐dose insulin injections; N, number of patients with data at both time points; OADs, oral antidiabetic drugs
Figure 3
Figure 3
Changes in total insulin and glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) dose from baseline to 6 months. Baseline is defined as last recorded insulin dose before insulin degludec/liraglutide combination (IDegLira) initiation. Data based on effectiveness analysis set. Significance assessed using a two‐tailed paired t test. DDD, defined daily dose; IU, international unit; MDI, multiple daily‐dose insulin injections; ns, non‐significant; OADs, oral antidiabetic drugs

References

    1. Greig SL, Scott LJ. Insulin degludec/liraglutide: a review in type 2 diabetes. Drugs. 2015;75(13):1523‐1534.
    1. Buse JB, Bergenstal RM, Glass LC, et al. Use of twice‐daily exenatide in basal insulin‐treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2011;154(2):103‐112.
    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(9):2489‐2496.
    1. Riddle MC, Forst T, Aronson R, et al. Adding once‐daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: a 24‐week, randomized, placebo‐controlled study (GetGoal‐Duo 1). Diabetes Care. 2013;36(9):2497‐2503.
    1. Ahmann A, Rodbard HW, Rosenstock J, et al. Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo‐controlled trial. Diabetes Obes Metab. 2015;17(11):1056‐1064.
    1. Mathieu C, Rodbard HW, Cariou B, et al. A comparison of adding liraglutide versus a single daily dose of insulin aspart to insulin degludec in subjects with type 2 diabetes (BEGIN: VICTOZA ADD‐ON). Diabetes Obes Metab. 2014;16(7):636‐644.
    1. Rosenstock J, Fonseca VA, Gross JL, et al. Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP‐1 receptor agonist, versus thrice‐daily prandial insulin lispro. Diabetes Care. 2014;37(8):2317‐2325.
    1. Diamant M, Nauck MA, Shaginian R, et al. Glucagon‐like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014;37(10):2763‐2773.
    1. American Diabetes Association . Standards of Medical Care in Diabetes‐2017 abridged for primary care providers. Clin Diabetes. 2017;35(1):5‐26.
    1. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm–2016 executive summary. Endocr Pract. 2016;22(1):84‐113.
    1. Hughes E. IDegLira: redefining insulin optimisation using a single injection in patients with type 2 diabetes. Prim Care Diabetes. 2016;10(3):202‐209.
    1. Novo Nordisk . Xultophy Summary of Product Characteristics. 2017. . Accessed July 31, 2017.
    1. Vedtofte L, Knop FK, Vilsboll T. Efficacy and safety of fixed‐ratio combination of insulin degludec and liraglutide (IDegLira) for the treatment of type 2 diabetes. Expert Opin Drug Saf. 2017;16(3):387‐396.
    1. Billings LD, Gouet D, Oviedo A, et al. Efficacy and safety of insulin degludec/liraglutide (IDegLira) vs. basal‐bolus (BB) therapy in patients with type 2 diabetes (T2D): DUAL VII trial. Diabetes. 2017;66(suppl 1A):A36 (Abstract 136‐OR).
    1. Buse JB, Vilsboll 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. Gough SC, Bode BW, Woo VC, et al. One‐year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26‐week extension to a 26‐week main trial. Diabetes Obes Metab. 2015;17(10):965‐973.
    1. Harris SB, Kocsis G, Prager R, et al. Safety and efficacy of IDegLira titrated once weekly versus twice weekly in patients with type 2 diabetes uncontrolled on oral antidiabetic drugs: DUAL VI randomized clinical trial. Diabetes Obes Metab. 2017;19(6):858‐865.
    1. Lingvay I, Pérez Manghi F, Garcia‐Hernandez P, et al. Effect of insulin glargine up‐titration vs insulin degludec/liraglutide on glycated hemoglobin levels in patients with uncontrolled type 2 diabetes: the DUAL V randomized clinical trial. JAMA. 2016;315(9):898‐907.
    1. Linjawi S, Bode BW, Chaykin LB, et al. The efficacy of IDegLira (insulin degludec/liraglutide combination) in adults with type 2 diabetes inadequately controlled with a GLP‐1 receptor agonist and oral therapy: DUAL III randomized clinical trial. Diabetes Ther. 2017;8(1):101‐114.
    1. Rodbard HW, Bode BW, Harris SB, et al. Safety and efficacy of IDegLira added to sulphonylureas alone or sulphonylureas and metformin in insulin‐naïve people with type 2 diabetes: the DUAL IV trial. Diabet Med. 2017;34(2):189‐196.
    1. Novo Nordisk . Xultophy® Prescribing Information (PI). 2016. . Accessed July 31, 2017.
    1. DUAL VIII trial. NLM identifier: NCT02501161. . Accessed July 31, 2017.
    1. DUAL IX trial. NLM identifier: NCT02773368. . Accessed July 31, 2017.
    1. Sofra D. Glycemic control in a real‐life setting in patients with type 2 diabetes treated with IDegLira at a Single Swiss Center. Diabetes Ther. 2017;8(2):377‐384.
    1. Wyatt K, Hall L. No or Aye to Xultophy? Experience of fixed combination insulin Degludec and Liraglutide in Wishaw General Hospital. Diabet Med. 2017;34(suppl s1):189‐194. (Abstract P511).
    1. World Medical Association . World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191‐2194.
    1. World Health Organization ATC/DDD Index 2017. . Accessed July 31, 2017.
    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.

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