BACKGROUND: Successful conversion from insulin therapy to glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in well-controlled patients has already been demonstrated. However, the data concerning individuals with poor glycaemic control are scarce. The aim of this work was to assess the success rate of insulin therapy to liraglutide transition in poorly controlled diabetes in a real-world clinical setting and to define predictors of success. We are the first to present the method of a fasting test as a way to identify the patients at higher risk of failure after treatment de-intensification. METHODS: The retrospective observational study analyzed data of 62 poorly controlled obese diabetic patients on high-dose insulin therapy, who were subjected to a 72 h fasting test during hospitalization and subsequently switched to liraglutide ± basal insulin therapy. During the fasting, all antidiabetic treatment was discontinued. Patients were classified as responders if they remained on GLP-1RA treatment after 12 months. Non-responders restarted the basal-bolus insulin (BBI) regimen. Development of glycated hemoglobin (HbA1c) and body weight in both groups, alongside with parameters associated with the higher risk of return to the BBI regimen, were analyzed. RESULTS: A total of 71% of patients were switched successfully (=responders). Responders had more significant improvement in HbA1c (-6.4 ± 19.7 vs. -3.4 ± 22.9 mmol/mol) and weight loss (-4.6 ± 7.1 vs. -2.5 ± 4.0). Statistically significant difference between groups was found in initial HbA1c (75.6 ± 17.9 vs. 90.5 ± 23.6; p = 0.04), total daily dose of insulin (67.6 ± 36.4 vs. 90.8 ± 32.4; p = 0.02), and mean glycaemia during the fasting test (6.9 ± 1.7 vs. 8.6 ± 2.2 mmol/L; p < 0.01). CONCLUSIONS: This study confirms that therapy de-intensification in poorly controlled patients with a BBI regimen is possible. Higher baseline HbA1c, total daily insulin dose, and mean glucose during fasting test are negative predictive factors of successful therapy de-escalation.

1st Department of Internal Medicine University Hospital Pilsen Charles University Faculty of Medicine in Pilsen 323 00 Pilsen Czech Republic

Zobrazit více v PubMed

Marso S.P., Daniels G.H., Brown-Frandsen K., Kristensen P., Mann J.F., Nauck M.A., Nissen S.E., Pocock S., Poulter N.R., Ravn L.S., et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N. Engl. J. Med. 2016;375:311–322. doi: 10.1056/NEJMoa1603827. PubMed DOI PMC

Gerstein H.C., Colhoun H.M., Dagenais G.R., Diaz R., Lakshmanan M., Pais P., Probstfield J., Riesmeyer J.S., Riddle M.C., Rydén L., et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): A double-blind, randomised placebo-controlled trial. Lancet. 2019;394:121–130. doi: 10.1016/S0140-6736(19)31149-3. PubMed DOI

Husain M., Bain S.C., Holst A.G., Mark T., Rasmussen S., Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: Combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc. Diabetol. 2020;19:156. doi: 10.1186/s12933-020-01106-4. PubMed DOI PMC

Lee Y.S., Jun H.S. Anti-diabetic actions of glucagon-like peptide-1 on pancreatic beta-cells. Metabolism. 2014;63:9–19. doi: 10.1016/j.metabol.2013.09.010. PubMed DOI

Buse J.B., Rosenstock J., Sesti G., Schmidt W.E., Montanya E., Brett J.H., Zychma M., Blonde L., LEAD-6 Study Group 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. doi: 10.1016/S0140-6736(09)60659-0. PubMed DOI

Eng C., Kramer C.K., Zinman B., Retnakaran R. 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;384:2228–2234. doi: 10.1016/S0140-6736(14)61335-0. PubMed DOI

Rosenstock J., Nino A., Soffer J., Erskine L., Acusta A., Dole J., Carr M.C., Mallory J., Home P. Impact of a Weekly Glucagon-Like Peptide 1 Receptor Agonist, Albiglutide, on Glycemic Control and on Reducing Prandial Insulin Use in Type 2 Diabetes Inadequately Controlled on Multiple Insulin Therapy: A Randomized Trial. Diabetes Care. 2020;43:2509–2518. doi: 10.2337/dc19-2316. PubMed DOI PMC

Taybani Z., Bótyik B., Katkó M., Gyimesi A., Várkonyi T. Simplifying Complex Insulin Regimens While Preserving Good Glycemic Control in Type 2 Diabetes. Diabetes Ther. 2019;10:1869–1878. doi: 10.1007/s13300-019-0673-8. PubMed DOI PMC

Bruinstroop E., Meyer L., Brouwer C.B., van Rooijen D.E., van Dam P.S. Retrospective Analysis of an Insulin-to-Liraglutide Switch in Patients with Type 2 Diabetes Mellitus. Diabetes Ther. 2018;9:1369–1375. doi: 10.1007/s13300-018-0438-9. PubMed DOI PMC

Horie I., Haraguchi A., Sako A., Akeshima J., Niri T., Shigeno R., Ito A., Nozaki A., Natsuda S., Akazawa S., et al. Predictive factors of efficacy of combination therapy with basal insulin and liraglutide in type 2 diabetes when switched from longstanding bas)al-bolus insulin: Association between the responses of β- and α-cells to GLP-1 stimulation and the glycaemic control at 6 months after switching therapy. Diabetes Res. Clin. Pract. 2018;144:161–170. doi: 10.1016/j.diabres.2018.08.015. PubMed DOI

Inoue Y., Nakamura A., Kondo Y., Hamano K., Satoh S., Terauchi Y. A randomized controlled trial of liraglutide versus insulin detemir plus sitagliptin: Effective switch from intensive insulin therapy to the once-daily injection in patients with well-controlled type 2 diabetes. J. Clin. Pharmacol. 2015;55:831–838. doi: 10.1002/jcph.483. PubMed DOI

Davies M.J., Aroda V.R., Collins B.S., Gabbay R.A., Green J., Maruthur N.M., Rosas S.E., Del Prato S., Mathieu C., Mingrone G., 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;45:2753–2786. doi: 10.2337/dci22-0034. PubMed DOI PMC

Bonora B.M., Rigato M., Frison V., D′Ambrosio M., Tadiotto F., Lapolla A., Simioni N., Paccagnella A., Avogaro A., Fadini G.P. Deintensification of basal-bolus insulin after initiation of GLP-1RA in patients with type 2 diabetes under routine care. Diabetes Res. Clin. Pract. 2021;173:108686. doi: 10.1016/j.diabres.2021.108686. PubMed DOI

Giugliano D., Longo M., Caruso P., Di Fraia R., Scappaticcio L., Gicchino M., Petrizzo M., Bellastella G., Maiorino M.I., Esposito K. 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;44:1353–1360. doi: 10.2337/dc20-2623. PubMed DOI PMC

Kawata T., Kanamori A., Kubota A., Maeda H., Amamiya H., Takai M., Kaneshige H., Minagawa F., Iemitsu K., Kaneshiro M., et al. Is a switch from insulin therapy to liraglutide possible in Japanese type 2 diabetes mellitus patients? J. Clin. Med. Res. 2014;6:138–144. doi: 10.14740/jocmr1719w. PubMed DOI PMC

Araki H., Tanaka Y., Yoshida S., Morita Y., Kume S., Isshiki K., Araki S., Uzu T., Kashiwagi A., Maegawa H. Oral glucose-stimulated serum C-peptide predicts successful switching from insulin therapy to liraglutide monotherapy in Japanese patients with type 2 diabetes and renal impairment. J. Diabetes Investig. 2014;5:435–441. doi: 10.1111/jdi.12169. PubMed DOI PMC

Lytrivi M., Castell A.L., Poitout V., Cnop M. Recent Insights into Mechanisms of β-Cell Lipo- and Glucolipotoxicity in Type 2 Diabetes. J. Mol. Biol. 2020;432:1514–1534. doi: 10.1016/j.jmb.2019.09.016. PubMed DOI PMC

Monami M., Dicembrini I., Nreu B., Andreozzi F., Sesti G., Mannucci E. Predictors of response to glucagon-like peptide-1 receptor agonists: A meta-analysis and systematic review of randomized controlled trials. Acta Diabetol. 2017;54:1101–1114. doi: 10.1007/s00592-017-1054-2. PubMed DOI

Usui R., Sakuramachi Y., Seino Y., Murotani K., Kuwata H., Tatsuoka H., Hamamoto Y., Kurose T., Seino Y., Yabe D. Retrospective analysis of liraglutide and basal insulin combination therapy in Japanese type 2 diabetes patients: The association between remaining β-cell function and the achievement of the glycated hemoglobin target 1 year after initiation. J. Diabetes Investig. 2018;9:822–830. doi: 10.1111/jdi.12773. PubMed DOI PMC