Advertisement

Drugs & Therapy Perspectives

, Volume 35, Issue 10, pp 470–480 | Cite as

Insulin glargine/lixisenatide in type 2 diabetes: a profile of its use

  • Emma DeeksEmail author
Adis Drug Q&A
  • 82 Downloads

Abstract

Subcutaneous insulin glargine/lixisenatide [Suliqua® 100/33 and 100/50 (EU); Soliqua® 100/33 (USA)] is a titratable, fixed-ratio combination of a long-acting basal insulin analogue + a glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved to treat inadequately controlled type 2 diabetes (T2D) in adults. Once-daily insulin glargine/lixisenatide provided glycaemic control better than that of insulin glargine or lixisenatide in insulin-naive patients (when added to metformin) and better than that of insulin glargine in insulin-experienced patients (when used ± metformin) in phase 3 trials in adults with inadequately controlled T2D. It also had a beneficial effect on bodyweight and did not increase the frequency of hypoglycaemia versus insulin glargine. Insulin glargine/lixisenatide is generally well tolerated and offers the convenience of once-daily administration of two subcutaneous antihyperglycaemic agents. It is, therefore, a valuable option for improving glycaemic control in adults with T2D when this has not been provided by metformin alone or metformin + another oral antihyperglycaemic agent or + basal insulin.

Notes

Acknowledgements

The manuscript was updated from Drugs 2017;17(12):1353–62 [15], and was reviewed by: S.C. Bain, Swansea University Medical School, Swansea, UK; G. Dimitriadis, 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University Medical School, Attikon University Hospital, Haidari, Greece; T. Tzotzas, St Luke’s General Hospital, Thessaloniki, Greece. During the peer review process, Sanofi-Aventis, the marketing-authorization holder of insulin glargine/lixisenatide, was also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with ethical standards

Funding

The preparation of this review was not supported by any external funding.

Conflicts of interest

Emma Deeks is an employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no conflicts of interest.

References

  1. 1.
    American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2018. Diabetes Care. 2019;41(Suppl 1):S13–27.CrossRefGoogle Scholar
  2. 2.
    Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centered approach. Update to position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38:140–9.CrossRefGoogle Scholar
  3. 3.
    American Diabetes Association. 6: Glycemic targets: standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S61–70.CrossRefGoogle Scholar
  4. 4.
    Riddle MC, Gerstein HC, Holman RR, et al. A1C targets should be personalized to maximize benefits while limiting risks. Diabetes Care. 2018;41(6):1121–4.CrossRefGoogle Scholar
  5. 5.
    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(12):2669–701.CrossRefGoogle Scholar
  6. 6.
    Milligan S. Combination therapy for improvement of long-term macrovascular and microvascular outcomes in type 2 diabetes: rationale and evidence for early initiation. J Diabetes Complications. 2016;30:1177–85.CrossRefGoogle Scholar
  7. 7.
    American Diabetes Association. 9. Pharmacological approaches to glycemic treatment: standards of medical care in diabetes - 2019. Diabetes Care. 2019;42(Suppl 1):S90–102.CrossRefGoogle Scholar
  8. 8.
    Apovian CM, Okemah J, O’Neil PM. Body weight considerations in the management of type 2 diabetes. Adv Ther. 2019;36(1):44–58.CrossRefGoogle Scholar
  9. 9.
    Levin PA. Practical combination therapy based on pathophysiology of type 2 diabetes. Diabetes Metab Syndr Obes. 2016;9:355–69.CrossRefGoogle Scholar
  10. 10.
    Wilding JPH, Bain SC. Role of incretin-based therapies and sodium-glucose co-transporter-2 inhibitors as adjuncts to insulin therapy in type 2 diabetes, with special reference to IDegLira. Diabet Med. 2016;33(7):864–76.CrossRefGoogle Scholar
  11. 11.
    Eng C, Kramer CK, Zinman B, et al. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis. Lancet. 2014;384:2228–34.CrossRefGoogle Scholar
  12. 12.
    Suliqua (insulin glargine 100 units/mL + lixisenatide 33 or 50 micrograms/mL) solution in a prefilled pen: summary of product characteristics. Paris: Sanofi-Aventis Groupe; 2019.Google Scholar
  13. 13.
    Soliqua 100/33 (insulin glargine and lixisenatide injection), for subcutaneous use: US prescribing information. Bridgewater (NJ): sanofi-aventis US LLC; 2019.Google Scholar
  14. 14.
    Porcellati F, Lucidi P, Cioli P, et al. Pharmacokinetics and pharmacodynamics of insulin glargine given in the evening as compared with in the morning in type 2 diabetes. Diabetes Care. 2015;38(3):503–12.CrossRefGoogle Scholar
  15. 15.
    Scott LJ. Insulin glargine/lixisenatide: a review in type 2 diabetes. Drugs. 2017;77(12):1353–62.CrossRefGoogle Scholar
  16. 16.
    Vidal J. Lixisenatide: a new glucagon-like peptide 1 receptor agonists in the treatment of type 2 diabetes. Eur Endocrinol. 2013;9(2):76–81.CrossRefGoogle Scholar
  17. 17.
    Meier JJ, Menge B, Schenker N, et al. Mechanisms of action of the glucose-lowering effect of lixisenatide in combination with insulin glargine [abstract no. 281-OR]. Diabetes. 2015;64(Suppl 1):A74.Google Scholar
  18. 18.
    Kovatchev B, Umpierrez G, Renard E. The differential and combined action of insulin glargine and lixisenatide on the fasting and post-prandial components of glucose control [abstract no. 3]. Diabetologia. 2016;59(Suppl 1):S2.Google Scholar
  19. 19.
    Tonneijck L, Muskiet MHA, Smits MM, et al. Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: an 8-week, randomised, open-label trial. Diabetes Obes Metab. 2017;19(12):1669–80.CrossRefGoogle Scholar
  20. 20.
    Tonneijck L, Muskiet MHA, Blijdorp CJ, et al. Renal tubular effects of prolonged therapy with the GLP-1 receptor agonist lixisenatide in patients with type 2 diabetes mellitus. Am J Physiol Renal Physiol. 2019;316(2):F231–40.CrossRefGoogle Scholar
  21. 21.
    Tonneijck L, Muskiet MHA, Twisk JW, et al. Lixisenatide versus insulin glulisine on fasting and postbreakfast systemic hemodynamics in type 2 diabetes mellitus patients. Hypertension. 2018;72(2):314–22.CrossRefGoogle Scholar
  22. 22.
    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):2026–35.CrossRefGoogle Scholar
  23. 23.
    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(11):1972–80.CrossRefGoogle Scholar
  24. 24.
    Ritzel R, Vidal J, Aroda VR, et al. Efficacy and safety across the final dose ranges in patients with T2DM receiving insulin glargine/lixisenatide fixed-ratio combination in the LixiLan-L trial [abstract no. 1024-P]. Diabetes. 2016;65(Suppl 1):A266–7.Google Scholar
  25. 25.
    Davis M, Leiter LA, Grunberger G, et al. Impact of baseline HbA1c, BMI, and diabetes duration on the efficacy and safety of LixiLan (insulin glargine/lixisenatide titratable fixed-ratio combination) vs. insulin glargine and lixisenatide in the LixiLan-O trial [abstract no. 1028-P]. Diabetes. 2016;65(Suppl 1):A268.Google Scholar
  26. 26.
    Wysham C, Bonadonna RC, Aroda VR, et al. Consistent findings in glycaemic control, body weight and hypoglycaemia with iGlarLixi (insulin glargine/lixisenatide titratable fixed-ratio combination) vs insulin glargine across baseline HbA1c, BMI and diabetes duration categories in the LixiLan-L trial. Diabetes Obes Metab. 2017;19(10):1408–15.CrossRefGoogle Scholar
  27. 27.
    Handelsman Y, Chovanes C, Dex T, et al. Efficacy and safety of insulin glargine/lixisenatide fixed-ratio combination in elderly patients with T2D [abstract no. 954-P]. Diabetes. 2016;65(Suppl 1):A246.Google Scholar
  28. 28.
    Niemoeller E, Souhami E, Wu Y, et al. iGlarLixi reduces glycated hemoglobin to a greater extent than basal insulin regardless of levels at screening: post hoc analysis of LixiLan-L. Diabetes Ther. 2018;9(1):373–82.CrossRefGoogle Scholar
  29. 29.
    Desouza C, Fonseca V, Frias JP, et al. Glycemic target attainment in insulin-naive patients with T2D receiving iglarlixi [abstract no. 1093-P]. Diabetes. 2018;67(Suppl 1):A291.Google Scholar
  30. 30.
    Giorgino F, Retnakaran R, Vidal J, et al. iGlarlixi effectively reduces residual hyperglycemia in patients with type 2 diabetes on basal insulin-a post-hoc analysis from the LixiLan-l study [abstract no. 1095-P]. Diabetes. 2018;67(Suppl 1):A292.Google Scholar
  31. 31.
    Mora P, Chao J, Saremi A, et al. Relationship of ethnicity to clinical outcomes in iglarlixi-treated patients with type 2 diabetes [abstract no. 1072-P]. Diabetes. 2018;67(Suppl 1):A284.Google Scholar
  32. 32.
    Dailey G, Bajaj HS, Dex T, et al. Post hoc efficacy and safety analysis of insulin glargine/lixisenatide fixed-ratio combination in North American patients compared with the rest of world. BMJ Open Diabetes Res Care. 2019;7(1).Google Scholar
  33. 33.
    Sugimoto DH, Dex T, Stager W, et al. Efficacy of iGlarLixi, a fixed-ratio combination of insulin glargine and lixisenatide, in patients with type 2 diabetes stratified as at high or low risk according to HEDIS measurements. Diabetes Obes Metab. 2018;20(11):2680–4.CrossRefGoogle Scholar
  34. 34.
    Aronson R, Umpierrez G, Stager W, et al. Insulin glargine/lixisenatide fixed-ratio combination improves glycaemic variability and control without increasing hypoglycaemia. Diabetes Obes Metab. 2019;21(3):726–31.Google Scholar
  35. 35.
    Zisman A, Dex T, Roberts M, et al. Bedtime-to-morning glucose difference and iGlarLixi in type 2 diabetes: post hoc analysis of LixiLan-L. Diabetes Ther. 2018;9(5):2155–62.CrossRefGoogle Scholar
  36. 36.
    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):1081–9.CrossRefGoogle Scholar
  37. 37.
    Davies MJ, Russell-Jones D, Barber TM, et al. Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial. Diabetes Obes Metab. 2019;21(8):1967–72.CrossRefGoogle Scholar
  38. 38.
    Blonde L, Berard L, Saremi A, et al. Impact of type 2 diabetes (T2D) duration on response to iglarlixi vs. Iglar:a subanalysis of LixiLan-L [abstract no. 1094-P]. Diabetes. 2018;67(Suppl 1):A291–2.Google Scholar
  39. 39.
    Leiter LA, Chao J, Saremi A, et al. A1c target attainment in patients with T2D receiving iGlarLixi who reach PPG and FPG targets in the Lixilan-L trial [abstract no. 1089-P]. Diabetes. 2018;67(Suppl 1):A290.Google Scholar
  40. 40.
    Frias JP, Dex T, Roberts M, et al. A review of the safety and adverse event profile of the fixed-ratio combination of insulin glargine and lixisenatide. Diabetes Ther. 2019;10(1):21–33.CrossRefGoogle Scholar
  41. 41.
    Trujillo JM, Roberts M, Dex T, et al. Low incidence of gastrointestinal adverse events over time with a fixed-ratio combination of insulin glargine and lixisenatide versus lixisenatide alone. Diabetes Obes Metab. 2018;20(11):2690–4.CrossRefGoogle Scholar
  42. 42.
    ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367(4):319–28.CrossRefGoogle Scholar
  43. 43.
    Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23):2247–57.CrossRefGoogle Scholar
  44. 44.
    Perreault L, Rodbard H, Valentine V, et al. Optimizing fixed-ratio combination therapy in type 2 diabetes. Adv Ther. 2019;36(2):265–77.CrossRefGoogle Scholar
  45. 45.
    Zannad F, Stough WG, Lipicky RJ, et al. Assessment of cardiovascular risk of new drugs for the treatment of diabetes mellitus: risk assessment vs. risk aversion. Eur Heart J. 2016;2:200–5.Google Scholar
  46. 46.
    Committee for Medicinal Products for Human Use (CHMP). Guidelines on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus: revision 1. London: European Medicines Agency; 2012.Google Scholar
  47. 47.
    Blumer I, Pettus JH, Santos Cavaiola T. Fixed-ratio combination therapy for type 2 diabetes: the top ten things you should know about insulin and glucagon-like peptide-1 receptor agonist combinations. Postgrad Med. 2018;130(4):375–80.CrossRefGoogle Scholar
  48. 48.
    Cai X, Gao X, Yang W, et al. Comparison between insulin degludec/liraglutide treatment and insulin glargine/lixisenatide treatment in type 2 diabetes: a systematic review and meta-analysis. Expert Opin Pharmacother. 2017;18(17):1789–98.CrossRefGoogle Scholar
  49. 49.
    Evans M, Billings LK, Hakan-Bloch J, et al. An indirect treatment comparison of the efficacy of insulin degludec/liraglutide (IDegLira) and insulin glargine/lixisenatide (iGlarLixi) in patients with type 2 diabetes uncontrolled on basal insulin. J Med Econ. 2018;21(4):340–7.CrossRefGoogle Scholar
  50. 50.
    Montagnoli R, Lastoria G, Parekh W, et al. Long-term cost-effectiveness analysis of IDegLira versus iGlarLixi for the treatment of patients with poorly controlled type 2 diabetes on basal insulin in the Italian setting [abstract no. PDB77]. Value Health. 2018;21(Suppl 3):S131.Google Scholar
  51. 51.
    Hvid C, Parekh W, Pohlmann J, et al. Cost-effectiveness of treating patients with type 2 diabetes poorly controlled on basal insulin with fixed-ratio combinations of basal insulin and Glp-1 receptor agonists in Denmark: IDegLira versus iGlarLixi [abstract no. PDB75 + poster]. Value Health. 2018;21(Suppl 3):S131.Google Scholar
  52. 52.
    Pohlmann J, Russel-Szymczyk M, Holik P, et al. Treating patients with type 2 diabetes mellitus uncontrolled on basal insulin in the Czech Republic: cost-effectiveness of IDegLira versus iGlarLixi. Diabetes Ther. 2019;10(2):493–508.CrossRefGoogle Scholar
  53. 53.
    Stryker MD, Blow CA, Friedman EB, et al. Assessing the real-world use of combination insulin glargine-lixisenatide in patients with type 2 diabetes mellitus:a retrospective review from an ambulatory care endocrinology practice [abstract no. 2290-PUB]. Diabetes. 2018;67(Suppl 1):A598.Google Scholar
  54. 54.
    Liakopoulou P, Liakos A, Vasilakou D, et al. Fixed ratio combinations of glucagon like peptide 1 receptor agonists with basal insulin: a systematic review and meta-analysis. Endocrine. 2017;56(3):485–94.CrossRefGoogle Scholar
  55. 55.
    Skolnik N, Hinnen D, Kiriakov Y, et al. Initiating titratable fixed-ratio combinations of basal insulin analogs and glucagon-like peptide-1 receptor agonists: what you need to know. Clin Diabetes. 2018;36(2):174–82.CrossRefGoogle Scholar
  56. 56.
    Rosenstock J, Handelsman Y, Vidal J, et al. Propensity-score-matched comparative analyses of simultaneously administered fixed-ratio insulin glargine 100 U and lixisenatide (iGlarLixi) vs sequential administration of insulin glargine and lixisenatide in uncontrolled type 2 diabetes. Diabetes Obes Metab. 2018;20(12):2821–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Springer NatureAucklandNew Zealand

Personalised recommendations