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De-intensification of basal-bolus insulin regimen after initiation of a GLP-1 RA improves glycaemic control and promotes weight loss in subjects with type 2 diabetes

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Abstract

Aims

To evaluate the impact of adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in people with type 2 diabetes (T2D) in basal-bolus (BB) insulin regimen, on insulin requirement, HbA1c, weight loss up to 24 months.

Methods

Data on subjects with T2D on BB who initiated a GLP-1 RA have been retrospectively collected. HbA1c, body weight, and insulin dose were recorded at baseline, 6, 12, and 24 months after initiation of GLP-1 RA therapy. A linear mixed model for repeated measures was used to evaluate the changes in HbA1c, body weight, and insulin requirement over time.

Results

We included 156 subjects (63.5% males; age 62 ± 11 years, HbA1c 70 ± 22.0 mmol/mol; 8.6 ± 4.2%). Compared to baseline, HbA1c and body weight were significantly lower at 6 months after introducing a GLP-1RA and remained stable up to 24 months (all p < 0.0001 vs. baseline). At 24 months, 81% of subjects discontinued prandial insulin, while 38.6% discontinued basal insulin as well. Insulin requirement at baseline (aOR 0.144; 95% CI, 0.046–0.456; P = 0.001) was the only significant predictor of prandial insulin discontinuation.

Conclusions

Replacing prandial insulin with GLP-1 RA is a valuable strategy to simplify the BB insulin regimen while improving glycaemic control and promoting weight loss in subjects with T2D.

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Data availability

The dataset generated during and/or analyzed during the current study is available from the corresponding author on reasonable request.

References

  1. Care D, Suppl SS (2022) 9 Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes. Diabetes Care 45:S125–S143. https://doi.org/10.2337/dc22-S009

    Article  Google Scholar 

  2. Basu S, Yudkin JS, Kehlenbrink S, Davies JI, Wild SH, Lipska KJ et al (2019) Estimation of globalinsulin use for type 2 diabetes, 2018–30: a microsimulation analysis. Lancet Diabetes Endocrinol 7:25–33. https://doi.org/10.1016/S2213-8587(18)30303-6

    Article  Google Scholar 

  3. Davies MJ, D’Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G et al (2018) Management of hyperglycaemia in type 2 diabetes a consensus report by the American diabetes association (ADA) and the European association for the study of diabetes (EASD). Diabetologia 61(12):2461–2498. https://doi.org/10.2337/dci18-0033

    Article  Google Scholar 

  4. Buse JB, Wexler DJ, Tsapas A, Rossing P, Mingrone G, Mathieu C et al (2020) Erratum: 2019 updateto: 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 43(2):487–493. https://doi.org/10.2337/dc20-er07

    Article  CAS  Google Scholar 

  5. Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M et al (2014) Glucagon-likepeptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care 37:2763–2773. https://doi.org/10.2337/dc14-0876

    Article  CAS  Google Scholar 

  6. Eng C, Kramer CK, Zinman B, Retnakaran R (2014) 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 384:2228–2234. https://doi.org/10.1016/S01406736(14)61335-0

    Article  CAS  Google Scholar 

  7. Maiorino MI, Chiodini P, Bellastella G, Capuano A, Esposito K, Giugliano D (2017) Insulin and glucagon-like peptide 1 receptor agonist combination therapy in type 2 diabetes: a systematic reviewand meta-analysis of randomized controlled trials. Diabetes Care 40:614–624. https://doi.org/10.2337/dc16-1957

    Article  Google Scholar 

  8. Aroda VR, Rosenstock J, Wysham C, Unger J, Bellido D, González-Gálvez G et al (2016) Efficacy and safety of LixiLan, a titratable fixed-ratio combination of insulin glargine plus lixisenatide in type 2diabetes inadequately controlled on basal insulin and metformin: the LixiLan-L randomized trial. Diabetes Care 39:1972–1980. https://doi.org/10.2337/dc16-1495

    Article  CAS  Google Scholar 

  9. Lingvay I, Manghi FP, García-Hernández P, Norwood P, Lehmann L, Tarp-Johansen MJ et al (2016) Effect of insulin glargine up-titration vs insulin degludec/liraglutide on glycated hemoglobin levelsin patients with uncontrolled type 2 diabetes: the DUAL v randomized clinical trial. JAMA J Am Med Assoc 315:898–907. https://doi.org/10.1001/jama.2016.1252

    Article  CAS  Google Scholar 

  10. Castellana M, Cignarelli A, Brescia F, Laviola L, Giorgino F (2019) GLP-1 receptor agonist added toinsulin versus basal-plus or basal-bolus insulin therapy in type 2 diabetes: a systematic review andmeta-analysis. Diabetes Metab Res Rev 35:e3082. https://doi.org/10.1002/dmrr.3082

    Article  CAS  Google Scholar 

  11. Bonora BM, Rigato M, Frison V, D’Ambrosio M, Tadiotto F, Lapolla A et al (2021) Deintensification of basal-bolus insulin after initiation of GLP-1RA in patients with type 2 diabetes under routine care. Diabetes Res Clin Pract 173:108686. https://doi.org/10.1016/j.diabres.2021.108686

    Article  CAS  Google Scholar 

  12. Rosenstock J, Nino A, Soffer J, Erskine L, Acusta A, Dole J et al (2020) Impact of a weeklyglucagon-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 43:2509–2518. https://doi.org/10.2337/DC19-2316

    Article  CAS  Google Scholar 

  13. Wilcox T, De Block C, Schwartzbard AZ, Newman JD (2020) Diabetic agents, from metformin tosglt2 inhibitors and glp1 receptor agonists: JACC focus seminar. J Am Coll Cardiol 75:1956–1974. https://doi.org/10.1016/j.jacc.2020.02.056

    Article  CAS  Google Scholar 

  14. Giugliano D, Longo M, Caruso P, Di Fraia R, Scappaticcio L, Gicchino M et al (2021) 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 44:1353–1360. https://doi.org/10.2337/DC20-2623

    Article  CAS  Google Scholar 

  15. Price H, Blüher M, Prager R, Phan TM, Thorsted BL, Schultes B (2018) Use and effectiveness of afixed-ratio combination of insulin degludec/liraglutide (IDegLira) in a real-world population withtype 2 diabetes: results from a European, multicentre, retrospective chart review study. Diabetes Obes Metab 20:954–962. https://doi.org/10.1111/dom.13182

    Article  CAS  Google Scholar 

  16. Hopton OM, Waterbury NV, Egge JA, Lund BC (2022) Clinical impact of GLP-1 receptor agonistsin veterans receiving basal-bolus insulin. Pharmacotherapy 42:45–52. https://doi.org/10.1002/phar.2648

    Article  CAS  Google Scholar 

  17. Yoon NM, Cavaghan MK, Brunelle RL, Roach P (2009) Exenatide added to insulin therapy: a retrospective review of clinical practice over two years in an academic endocrinology outpatient setting. Clin Ther 31:1511–1523. https://doi.org/10.1016/j.clinthera.2009.07.021

    Article  CAS  Google Scholar 

  18. Taybani Z, Bótyik B, Katkó M, Gyimesi A, Várkonyi T (2019) Simplifying complex insulin regimenswhile preserving good glycemic control in type 2 diabetes. Diabetes Ther 10:1869–1878. https://doi.org/10.1007/S13300-019-0673-8

    Article  CAS  Google Scholar 

  19. Nauck MA, Quast DR, Wefers J, Meier JJ (2021) GLP-1 receptor agonists in the treatment of type 2diabetes–state-of-the-art. Mol Metab 46:101102. https://doi.org/10.1016/j.molmet.2020.101102

    Article  CAS  Google Scholar 

  20. Jones AG, McDonald TJ, Shields BM, Hill AV, Hyde CJ, Knight BA et al (2016) Markers of β-cellfailure predict poor glycemic response to GLP-1 receptor agonist therapy in type 2 diabetes. Diabetes Care 39:250–257. https://doi.org/10.2337/dc15-0258

    Article  CAS  Google Scholar 

  21. Del Prato S, Frias JP, Blonde L, Aroda VR, Shehadeh N, Saremi A et al (2020) Impact of disease duration and β-cell reserve on the efficacy of switching to iGlarLixi in adults with type 2 diabeteson glucagon-like peptide-1 receptor agonist therapy: exploratory analyses from the LixiLan-G trial. Diabetes Obes Metab 22(9):1567–1576. https://doi.org/10.1111/dom.14068

    Article  CAS  Google Scholar 

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Pierpaolo Falcetta and Francesca Nicolì have contributed equally to this paper.

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, 56124, Pisa, Italy

    Pierpaolo Falcetta, Francesca Nicolì, Fabrizia Citro, Monia Garofolo & Stefano Del Prato

  2. Department of Medicine, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy

    Annamaria Ciccarone & Cristina Bianchi

Authors
  1. Pierpaolo Falcetta
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  2. Francesca Nicolì
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  3. Fabrizia Citro
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  4. Annamaria Ciccarone
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  5. Monia Garofolo
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  6. Stefano Del Prato
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  7. Cristina Bianchi
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Contributions

PF, FN and CB contributed to the conception of the study, researched data and wrote the manuscript. FC, AC, MG and SDP contributed to the acquisition and interpretation of clinical data and critically reviewed the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Cristina Bianchi.

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Conflict of interest

PF, FN, FC, AC reports no duality of interest. MG reports consulting fees from Lilly. SDP declares grants from AstraZeneca and Boehringer Ingelheim, consulting fees from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharpe and Dohme, Novartis Pharmaceuticals, Novo Nordisk and Sanofi, and honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharpe and Dohme, Novartis Pharmaceuticals, Novo Nordisk and Sanofi. CB reports consulting fees and grants from Lilly, Novo Nordisk, Roche Diagnostics.

Ethics approval and informed consent

The study protocol was approved by the local Ethics Committee of the University of Pisa and conducted in accordance with the Declaration of Helsinki. Since data were anonymous and used in aggregated form no subjects’ informed consent was needed according to local ethic committee indications.

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Falcetta, P., Nicolì, F., Citro, F. et al. De-intensification of basal-bolus insulin regimen after initiation of a GLP-1 RA improves glycaemic control and promotes weight loss in subjects with type 2 diabetes. Acta Diabetol 60, 53–60 (2023). https://doi.org/10.1007/s00592-022-01974-0

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  • DOI: https://doi.org/10.1007/s00592-022-01974-0

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