INTRODUCTION: Multiple daily injection insulin regimen (MDI) represents the most intensive insulin regimen used in the management of people with type 2 diabetes (PwT2D). Its efficacy regarding glycaemic control is counterbalanced by the increased risk of hypoglycaemia, frequently observed tendency to weight gain and necessity for frequent glucose monitoring. Recent introduction of novel antidiabetic medications with pleiotropic effects reaching far beyond the reduction of glycaemia (HbA1c), such as the glucagon-like peptide 1 receptor agonist (GLP-1 RA), has significantly widened the therapeutic options available for management of T2D. Consequently, there is currently a substantial number of PwT2D for whom the MDI regimen was initiated at a time when no other options were available. Yet, in present times, these individuals could benefit from simplified insulin regimens ideally taking advantage of the beneficial effects of the novel classes of antidiabetic medications. iGlarLixi (Suliqua®) is a once-daily fixed-ratio combination of basal insulin analogue glargine 100 U/ml and a GLP-1 RA lixisenatide. METHODS: Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) is a six-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period examining the efficacy and safety of MDI regimen de-intensification with once-daily administration of iGlarLixi versus MDI regimen continuation in PwT2D on a backgroud therapy with metformin ± sodium-glucose cotransporter 2 inhibitor. PLANNED OUTCOMES: The primary objective is to compare the effects of MDI therapy de-intensification with iGlarLixi versus MDI regimen continuation regarding glycaemic control (HbA1c). Secondary objectives include detailed evaluation of the effects of MDI regimen de-intensification with iGlarLixi on glycaemic control using standardised continuous glucose monitoring (CGM) metrics and self-monitoring of plasma glucose. Furthermore, body weight and body composition analysis, quality of life and safety profile are evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04945070.

1st Department of Endocrinology Dr Réthy Pál Member Hospital Békes County Central Hospital Békéscsaba Hungary

1st Faculty of Medicine Charles University Prague Czech Republic

Department of Oncology and Metabolism University of Sheffield Sheffield UK

Diabetes Centre Institute for Clinical and Experimental Medicine Vídeňská 1958 140 21 Prague 4 Czech Republic

General Medicines Sanofi Paris France

Sanofi Hungary Budapest Hungary

Sanofi Prague Czech Republic

See more in PubMed

Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetologia. 2012;55(6):1577–1596. doi: 10.1007/s00125-012-2534-0. PubMed DOI

Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015;58(3):429–442. doi: 10.1007/s00125-014-3460-0. PubMed DOI

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):2669–2701. doi: 10.2337/dci18-0033. PubMed DOI PMC

Buse JB, Wexler DJ, Tsapas A, et al. 2019 update to: 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. 2020;43(2):487–493. doi: 10.2337/dci19-0066. PubMed DOI PMC

Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Care. 2022;45(11):2753–2786. doi: 10.2337/dci22-0034. PubMed DOI PMC

Defronzo RA. Banting lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):773–795. doi: 10.2337/db09-9028. PubMed DOI PMC

Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012;8(12):728–742. doi: 10.1038/nrendo.2012.140. PubMed DOI

Novodvorsky P, Haluzik M. An update on the safety of insulin-GLP-1 receptor agonist combinations in type 2 diabetes mellitus. Expert Opin Drug Saf. 2021 doi: 10.1080/14740338.2021.1978974. PubMed DOI

Sanofi. Suliqua summary of product characteristics 2020. Available from: https://www.medicines.org.uk/emc/product/9871/smpc. Accessed 28 Feb 2024.

Hilgenfeld R, Seipke G, Berchtold H, Owens DR. The evolution of insulin glargine and its continuing contribution to diabetes care. Drugs. 2014;74(8):911–927. doi: 10.1007/s40265-014-0226-4. PubMed DOI PMC

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(9):1579–1586. doi: 10.2337/dc16-0046. PubMed DOI PMC

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. doi: 10.2337/dc16-0917. PubMed DOI

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):1972–1980. doi: 10.2337/dc16-1495. PubMed DOI

Blonde L, Rosenstock J, Del Prato S, et al. Switching to iGlarLixi versus continuing daily or weekly GLP-1 RA in type 2 diabetes inadequately controlled by GLP-1 RA and oral antihyperglycemic therapy: the LixiLan-G randomized clinical trial. Diabetes Care. 2019;42(11):2108–2116. doi: 10.2337/dc19-1357. PubMed DOI

McCrimmon RJ, Al Sifri S, Emral R, et al. Advancing therapy with iGlarLixi versus premix BIAsp 30 in basal insulin-treated type 2 diabetes: design and baseline characteristics of the SoliMix randomized controlled trial. Diabetes Obes Metab. 2021;23(6):1221–1231. doi: 10.1111/dom.14354. PubMed DOI

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. doi: 10.1016/S2213-8587(14)70174-3. PubMed DOI

Taybani Z, Botyik B, Katko M, Gyimesi A, Varkonyi T. Simplifying complex insulin regimens while preserving good glycemic control in type 2 diabetes. Diabetes Ther. 2019;10(5):1869–1878. doi: 10.1007/s13300-019-0673-8. PubMed DOI PMC

Taybani ZJ, Botyik B, Gyimesi A, Katko M, Varkonyi T. One-year safety and efficacy results of insulin treatment simplification with IDegLira in type 2 diabetes. Endocrinol Diabetes Metab. 2023;6(1):e390. doi: 10.1002/edm2.390. PubMed DOI PMC

Martinka E, Dravecka I, Tkac I. Switching from multiple insulin injections to a fixed combination of degludec and liraglutide in patients with type 2 diabetes mellitus: results from the simplify study after 6 months. Diabetes Ther. 2023;14(9):1503–1515. doi: 10.1007/s13300-023-01435-z. PubMed DOI PMC

Giugliano D, Longo M, Caruso P, et al. Feasibility of simplification from a basal-bolus insulin regimen to a fixed-ratio formulation of basal insulin plus a GLP-1RA or to basal insulin plus an SGLT2 inhibitor: BEYOND, a randomized. Pragmatic Trial Diabetes Care. 2021;44(6):1353–1360. doi: 10.2337/dc20-2623. PubMed DOI PMC

Battelino T, Danne T, Bergenstal RM, et al. Clinical targets for continuous glucose monitoring data interpretation: recommendations from the international consensus on time in range. Diabetes Care. 2019;42(8):1593–1603. doi: 10.2337/dci19-0028. PubMed DOI PMC

Battelino T, Alexander CM, Amiel SA, et al. Continuous glucose monitoring and metrics for clinical trials: an international consensus statement. Lancet Diabetes Endocrinol. 2023;11(1):42–57. doi: 10.1016/S2213-8587(22)00319-9. PubMed DOI

See more in PubMed

ClinicalTrials.gov
NCT04945070