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Third-Line Antidiabetic Therapy Intensification Patterns and Glycaemic Control in Patients with Type 2 Diabetes in the USA: A Real-World Study

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Abstract

Background

Third-line antidiabetic drug (ADD) intensification patterns and glycemic control post intensification in type 2 diabetes mellitus (T2DM) have not been thoroughly explored in a real-world setting.

Objective

This study explored the patterns and risks of third-line ADD intensification post second-line ADDs and the probability of desirable glucose control over 12 months by third-line ADD classes at the population level.

Methods

We used the electronic medical records of 255,236 patients with T2DM in the USA initiating a second-line ADD post metformin from January 2013 to evaluate the rates and risks of third-line intensification and the probability of desirable glycemic control with different ADDs after addressing inherent heterogeneity using appropriate methodologies.

Results

Patients had a mean age of 60 years and glycated hemoglobin (HbA1c) of 8.5% at second-line ADD. Over 209,136 person-years (PY) of follow-up, 40% had initiated a third-line ADD at HbA1c of 8.8%. Patients receiving dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as the second-line ADD had a 7% (95% hazard ratio [HR] confidence interval [CI] 1.05–1.10) and 28% (95% HR CI 1.24–1.33) higher adjusted risk of intensifying with a third-line ADD than did those receiving sulfonylureas as the second-line ADD. Those receiving sodium-glucose cotransporter-2 inhibitors (SGLT-2i) as second-line ADD had a 17% (95% HR CI 0.80–0.87) lower risk. The adjusted probability of reducing HbA1c by ≥ 1% was similar in those receiving third-line sulfonylureas, thiazolidinediones, GLP-1 RAs, SGLT-2i, and insulin (minimum, maximum 95% CI of probability 0.61, 0.68), whereas those receiving DPP-4i had a significantly lower probability (0.58; 95% CI 0.56–0.59). Similarly, the probability of reducing HbA1c < 7.5% was similar in the sulfonylurea, GLP-1 RA, and SGLT-2i groups (minimum, maximum of 95% CI of probability 0.41, 0.49), whereas those receiving DPP-4i had a significantly lower probability of achieving an HbA1c < 7.5% (0.37; 95% CI 0.36–0.38).

Conclusion

This study, based on a large representative cohort of patients with T2DM from the USA, suggests the need for revisiting real-world practices in choosing therapeutic intensification pathways and a more proactive strategy to tackle the persistent risk factor burden in patients with T2DM.

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Acknowledgements

DNK, OM, and SKP were responsible for the primary design of the study. OM extracted the data. DNK and SKP jointly conducted the statistical analyses. The first draft of the manuscript was developed by DNK and SKP, and all authors contributed to the finalization of the manuscript. SKP had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Melbourne EpiCentre gratefully acknowledges the support from the National Health and Medical Research Council and the Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) initiative through Therapeutic Innovation Australia.

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Correspondence to Sanjoy Ketan Paul.

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Funding

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

Conflicts of interest

SKP has acted as a consultant and/or speaker for Novartis, GI Dynamics, Roche, AstraZeneca, Sanofi, Guangzhou Zhongyi Pharmaceutical, and Amylin Pharmaceuticals LLC. He has received grants in support of investigator and investigator-initiated clinical studies from Merck, Novo Nordisk, AstraZeneca, Hospira, Amylin Pharmaceuticals, Sanofi, and Pfizer. DNK and OM have no conflicts of interest that are directly relevant to the content of this article.

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Koye, D.N., Montvida, O. & Paul, S.K. Third-Line Antidiabetic Therapy Intensification Patterns and Glycaemic Control in Patients with Type 2 Diabetes in the USA: A Real-World Study. Drugs 80, 477–487 (2020). https://doi.org/10.1007/s40265-020-01279-y

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  • DOI: https://doi.org/10.1007/s40265-020-01279-y

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