INTRODUCTION: iGlarLixi (insulin glargine 100 U/mL plus lixisenatide) has demonstrated glycaemic efficacy and safety in adults with inadequately controlled type 2 diabetes mellitus (T2DM). Per the European Medicines Agency's product label, iGlarLixi should be injected once a day within 1 h prior to a meal, preferably the same meal every day when the most convenient meal has been chosen. It is however unknown whether iGlarLixi administration timing affects glycaemic control and safety, as clinical trial evidence is mainly based on pre-breakfast iGlarLixi administration. Therefore, we assessed the effectiveness and safety of iGlarLixi in clinical practice, according to its administration timing. METHODS: Data were pooled from two prospective observational studies including 1303 European participants with T2DM inadequately controlled on oral antidiabetic drugs with or without basal insulin who initiated iGlarLixi therapy for 24 weeks. Participants were classified into four subgroups based on daily timing of iGlarLixi injection: pre-breakfast (N = 436), pre-lunch (N = 262), pre-dinner (N = 399), and those who switched iGlarLixi injection time during the study (N = 206). RESULTS: No meaningful differences in baseline characteristics were observed between the study groups. Least-squares mean reductions in haemoglobin A1c (HbA1c) from baseline to week 24 were substantial in all groups, with the numerically largest decrease observed in the pre-breakfast group (1.57%) compared with the pre-lunch (1.27%), pre-dinner (1.42%), or changed injection time (1.33%) groups. Pre-breakfast iGlarLixi injection also resulted in a numerically greater proportion of participants achieving HbA1c < 7.0% at week 24 (33.7% versus 19.0% for pre-lunch, 25.6% pre-dinner, and 23.2% changed injection time). iGlarLixi was well tolerated across all groups, with low rates of gastrointestinal disorders and hypoglycaemia. Mean body weight decreased similarly in all groups (by 1.3-2.3 kg). CONCLUSION: iGlarLixi was effective and safe regardless of its daily administration time. However, pre-breakfast iGlarLixi injection resulted in a more effective glycaemic control.

Department of Diabetes Nutrition and Metabolic Diseases Carol Davila University of Medicine and Pharmacy Bucharest Romania

Department of Internal Medicine Centrum Szent János Hospital Budapest Hungary

Division of Endocrinology and Diabetology Department of Medicine 2 Medical Centre Faculty of Medicine University of Freiburg Freiburg Germany

General Medicines Sanofi Paris France

Institute for Clinical and Experimental Medicine and Charles University Prague Czech Republic

Institute of Clinical Trials and Methodology University College London London UK

International Drug Development Institute Louvain la Neuve Belgium

IVIDATA Group Paris France

See more in PubMed

Skolnik N, Del Prato S, Blonde L, Galstyan G, Rosenstock J. Translating iGlarLixi evidence for the management of frequent clinical scenarios in type 2 diabetes. Adv Ther. 2021;38(4):1715–1731. doi: 10.1007/s12325-020-01614-5. PubMed DOI PMC

Giorgino F, Caruso I, Napoli R. Titratable fixed-ratio combination of insulin glargine plus lixisenatide: a simplified approach to glycemic control in type 2 diabetes mellitus. Diabetes Res Clin Pract. 2020;170:108478. doi: 10.1016/j.diabres.2020.108478. PubMed DOI

Novodvorský P, Haluzík M. An update on the safety of insulin-GLP-1 receptor agonist combinations in type 2 diabetes mellitus. Expert Opin Drug Saf. 2022;21(3):349–361. doi: 10.1080/14740338.2021.1978974. 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

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

American Diabetes Association Professional Practice Committee, American Diabetes Association Professional Practice Committee. Draznin B, Aroda VR, et al. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Supplement 1):S125–S143. PubMed

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

Rosenstock J, Emral R, Sauque-Reyna L, et al. Advancing therapy in suboptimally controlled basal insulin-treated type 2 diabetes: clinical outcomes with iGlarLixi versus premix BIAsp 30 in the SoliMix randomized controlled trial. Diabetes Care. 2021;44(10):2361–2370. doi: 10.2337/dc21-0393. PubMed DOI PMC

Food and Drug Administration. Soliqua® 100/33: Prescribing Information. 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208673s011lbl.pdf. Accessed 8 Aug 2022.

European Medicines Agency. Suliqua: EPAR-Product information. 2022. https://www.ema.europa.eu/en/documents/product-information/suliqua-epar-product-information_en.pdf. Accessed 4 Mar 2022.

Kis JT, Nagy G, Kovacs G. Effectiveness of iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, in people with type 2 diabetes. Diabetes Ther. 2021;12(9):2517–2529. doi: 10.1007/s13300-021-01128-5. PubMed DOI PMC

Bala C, Cerghizan A, Mihai BM, Moise M, Guja C. Real-world evidence on the use of a fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) in people with suboptimally controlled type 2 diabetes in Romania: a prospective cohort study (STAR.Ro) BMJ Open. 2022;12(5):e060852. doi: 10.1136/bmjopen-2022-060852. PubMed DOI PMC

Freemantle N, Bonadonna RC, Gourdy P, et al. Rationale and methodology for a European pooled analysis of postmarketing interventional and observational studies of insulin glargine 300 U/mL in diabetes: protocol of REALI project. BMJ Open. 2020;10(4):e033659. doi: 10.1136/bmjopen-2019-033659. PubMed DOI PMC

Bonadonna RC, Mauricio D, Müller-Wieland D, et al. Impact of age on the effectiveness and safety of insulin glargine 300 U/mL: results from the REALI European pooled data analysis. Diabetes Ther. 2021;12(4):1073–1097. doi: 10.1007/s13300-021-01030-0. PubMed DOI PMC

Gourdy P, Bonadonna RC, Freemantle N, et al. Does gender influence the effectiveness and safety of insulin glargine 300 U/ml in patients with uncontrolled type 2 diabetes? Results from the REALI European pooled analysis. Diabetes Ther. 2022;13(1):57–73. doi: 10.1007/s13300-021-01179-8. PubMed DOI PMC

Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013;36(5):1384–1395. doi: 10.2337/dc12-2480. PubMed DOI PMC

Kapitza C, Forst T, Coester HV, Poitiers F, Ruus P, Hincelin-Méry A. Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin. Diabetes Obes Metab. 2013;15(7):642–649. doi: 10.1111/dom.12076. PubMed DOI PMC

Haluzík M, Flekač M, Lengyel C, et al. Expert opinion on the therapeutic use of the fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide: a central/eastern European perspective. Diabetes Ther. 2020;11(4):1029–1043. doi: 10.1007/s13300-020-00777-2. PubMed DOI PMC

Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger PM. Factors associated with injection omission/non-adherence in the Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabetes Obes Metab. 2012;14(12):1081–1087. doi: 10.1111/j.1463-1326.2012.01636.x. PubMed DOI

Davies MJ, Gagliardino JJ, Gray LJ, Khunti K, Mohan V, Hughes R. Real-world factors affecting adherence to insulin therapy in patients with type 1 or type 2 diabetes mellitus: a systematic review. Diabet Med. 2013;30(5):512–524. doi: 10.1111/dme.12128. PubMed DOI

Ahrén B, Leguizamo Dimas A, Miossec P, Saubadu S, Aronson R. Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M) Diabetes Care. 2013;36(9):2543–2550. doi: 10.2337/dc12-2006. PubMed DOI PMC

Ahrén B, Vorokhobina N, Souhami E, Demil N, Ye J, Aronson R. Equal improvement in glycaemia with lixisenatide given before breakfast or the main meal of the day. J Diabetes Complicat. 2014;28(5):735–741. doi: 10.1016/j.jdiacomp.2014.05.012. PubMed DOI

Gautier T, Silwal R, Saremi A, Boss A, Breton MD. Modeling the effect of subcutaneous lixisenatide on glucoregulatory endocrine secretions and gastric emptying in type 2 diabetes to simulate the effect of iGlarLixi administration timing on blood sugar profiles. J Diabetes Sci Technol. 2022;16(2):428–433. doi: 10.1177/19322968211015671. PubMed DOI PMC

Dailey G, Bajaj HS, Dex T, Groleau M, Stager W, Vinik A. 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):e000581. doi: 10.1136/bmjdrc-2018-000581. PubMed DOI PMC

Real-Life Effectiveness of iGlarLixi (Insulin Glargine 100 U/ml and Lixisenatide) in People with Type 2 Diabetes (T2D) According to Baseline HbA1c and BMI