Safety and efficacy of the combination of the glucagon-like peptide-1 receptor agonist liraglutide with an oral antidiabetic drug in Japanese patients with type 2 diabetes: Post-hoc analysis of a randomized, 52-week, open-label, parallel-group trial

Arihiro Kiyosue, Yutaka Seino, Keiji Nishijima, Heidrun Bosch-Traberg, Kohei Kaku, Arihiro Kiyosue, Yutaka Seino, Keiji Nishijima, Heidrun Bosch-Traberg, Kohei Kaku

Abstract

Aims/introduction: The aim of the present post-hoc analysis was to investigate the safety and efficacy of liraglutide in combination with one oral antidiabetic drug (OAD) across different OAD classes.

Materials and methods: This was a post-hoc analysis using data from a 52-week, open-label, parallel-group trial, in which patients with type 2 diabetes inadequately controlled with a single OAD (α-glucosidase inhibitor, glinide, metformin or thiazolidinedione) were randomized to either pretrial OAD in combination with liraglutide 0.9 mg/day (liraglutide group) or pretrial OAD in combination with an additional OAD (additional OAD group). The primary outcome investigated in this post-hoc analysis was the incidence of adverse events.

Results: The proportions of patients experiencing adverse events across the different groups of pretrial OADs were comparable between liraglutide and additional OAD (α-glucosidase inhibitor 74.6 vs 70.0%; glinide 93.1 vs 87.1%; metformin 91.8 vs 87.1%; thiazolidinedione 86.2 vs 96.4%, respectively). Minor hypoglycemia was infrequent (seven episodes in two patients randomized to liraglutide, and two episodes in two patients randomized to additional OAD). The mean reduction in glycated hemoglobin appeared greater with liraglutide therapy, with the estimated mean treatment difference (95% confidence interval [CI]) for liraglutide vs additional OAD ranging from -0.14%, 95% CI: -0.48 to 0.21 (-1.5 mmol/mol, 95 CI: -5.2 to 2.3) to -0.44%, 95% CI:-0.79 to -0.09 (-4.8 mmol/mol, 95% CI: -8.6 to -1.0).

Conclusions: The present analysis suggests that Japanese patients on OAD monotherapy might benefit from a greater improvement in glycemic control, without impacting tolerability, by combining their OAD with liraglutide rather than another OAD, regardless of which OAD monotherapy they are receiving.

Keywords: Glucagon-like peptide-1 receptor agonist; Liraglutide; Type 2 diabetes.

© 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

References

    1. García‐Pérez L‐E, Álvarez M, Dilla T, et al Adherence to therapies in patients with type 2 diabetes. Diabetes Ther 2013; 4: 175–194.
    1. ADA . Standards of medical care in diabetes – 2017. Diabetes Care 2017; 40(Suppl 1): S1–S2.
    1. Stein SA, Lamos EM, Davis SN. A review of the efficacy and safety of oral antidiabetic drugs. Expert Opin Drug Saf 2013; 12: 153–175.
    1. Japan Diabetes Society (ed.). Treatment Guide for Diabetes 2012–2013. Available from: Accessed February 1, 2016.
    1. Nauck M. Incretin therapies: highlighting common features and differences in the modes of action of glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors. Diabetes Obes Metab 2016; 18: 203–216.
    1. Marre M, Shaw J, Brandle M, et al Liraglutide, a once‐daily human GLP‐1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD‐1 SU). Diabet Med 2009; 26: 268–278.
    1. Nauck M, Frid A, Hermansen K, et al Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)‐2 study. Diabetes Care 2009; 32: 84–90.
    1. Garber A, Henry R, Ratner R, et al Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD‐3 Mono): a randomised, 52‐week, phase III, double‐blind, parallel‐treatment trial. Lancet 2009; 373: 473–481.
    1. Zinman B, Gerich J, Buse JB, et al Efficacy and safety of the human glucagon‐like peptide‐1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD‐4 Met+TZD). Diabetes Care 2009; 32: 1224–1230.
    1. Russell‐Jones D, Vaag A, Schmitz O, et al Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD‐5 met+SU): a randomised controlled trial. Diabetologia 2009; 52: 2046–2055.
    1. Buse JB, Rosenstock J, Sesti G, et al Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26‐week randomised, parallel‐group, multinational, open‐label trial (LEAD‐6). Lancet 2009; 374: 39–47.
    1. Pratley RE, Nauck M, Bailey T, et al Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26‐week, randomised, parallel‐group, open‐label trial. Lancet 2010; 375: 1447–1456.
    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: 1056–1064.
    1. DeVries JH, Bain SC, Rodbard HW, et al Sequential intensification of metformin treatment in type 2 diabetes with liraglutide followed by randomized addition of basal insulin prompted by A1C targets. Diabetes Care 2012; 35: 1446–1454.
    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: 636–644.
    1. Kaku K, Rasmussen MF, Clauson P, et al Improved glycaemic control with minimal hypoglycaemia and no weight change with the once‐daily human glucagon‐like peptide‐1 analogue liraglutide as add‐on to sulphonylurea in Japanese patients with type 2 diabetes. Diabetes Obes Metab 2010; 12: 341–347.
    1. Seino Y, Rasmussen MF, Nishida T, et al Glucagon‐like peptide‐1 analog liraglutide in combination with sulfonylurea safely improves blood glucose measures vs sulfonylurea monotherapy in Japanese patients with type 2 diabetes: results of a 52‐week, randomized, multicenter trial. J Diabetes Investig 2011; 2: 280–286.
    1. Kaku K, Kiyosue A, Ono Y, et al Liraglutide is effective and well tolerated in combination with an oral antidiabetic drug in Japanese patients with type 2 diabetes: a randomized, 52‐week, open‐label, parallel‐group trial. J Diabetes Investig 2016; 7: 76–84.
    1. Seino Y, Kaneko S, Fukuda S, et al Combination therapy with liraglutide and insulin in Japanese patients with type 2 diabetes: a 36‐week, randomized, double‐blind, parallel‐group trial. J Diabetes Investig 2016; 7: 565–573.
    1. Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. Last amended by the 59th WMA General Assembly, Seoul. World Medical Association 2008.
    1. International Conference on Harmonisation. ICH Harmonised Tripartite Guideline. Good Clinical Practice. 1 May 1996. Available from: Accessed January 26, 2017.
    1. American Diabetes Association . Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 2005; 28: 1245–1249.
    1. Japanese Ministry of Health, Labor and Welfare . Guideline for Clinical Evaluation of Oral Hypoglycemic Agents, 9 July 2010. Available from: Accessed January 26, 2017.
    1. Inzucchi SE, Bergenstal RM, Buse JB, et al Management of hyperglycemia in type 2 diabetes, 2015: a patient‐centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015; 38: 140–149.
    1. Blonde L, Russell‐Jones D. The safety and efficacy of liraglutide with or without oral antidiabetic drug therapy in type 2 diabetes: an overview of the LEAD 1‐5 studies. Diabetes Obes Metab 2009; 11(Suppl 3): 26–34.
    1. Shyangdan DS, Royle P, Clar C, et al Glucagon‐like peptide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev 2011: CD006423.
    1. Wilding J. Thiazolidinediones, insulin resistance and obesity: finding a balance. Int J Clin Pract 2006; 60: 1272–1280.
    1. Seino Y, Rasmussen MF, Nishida T, et al Efficacy and safety of the once‐daily human GLP‐1 analogue, liraglutide, vs glibenclamide monotherapy in Japanese patients with type 2 diabetes. Curr Med Res Opin 2010; 26: 1013–1022.
    1. Kaku K, Rasmussen MF, Nishida T, et al Fifty‐two‐week, randomized, multicenter trial to compare the safety and efficacy of the novel glucagon‐like peptide‐1 analog liraglutide vs glibenclamide in patients with type 2 diabetes. J Diabetes Investig 2011; 2: 441–447.

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