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Department of Family Medicine and Community Health

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Endocrine System Diseases | Endocrinology, Diabetes, and Metabolism | Epidemiology | Health Economics | Health Services Administration | Nutritional and Metabolic Diseases


We compared risks of clinical outcomes, mortality and healthcare costs among new users of different classes of anti-diabetic medications. This is a population-based, retrospective, new-user design cohort study using the Taiwan National Health Insurance Database between May 2, 2015 and September 30, 2017. An individual was assigned to a medication group based on the first anti-diabetic prescription on or after May 1, 2016: SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists or older agents (metformin, etc.). Clinical outcomes included lower extremity amputation, peripheral vascular disease, critical limb ischemia, osteomyelitis, and ulcer. We built three Cox proportional hazards models for clinical outcomes and mortality, and three regression models with a log-link function and gamma distribution for healthcare costs, all with propensity-score weighting and covariates. We identified 1,222,436 eligible individuals. After adjustment, new users of SGLT-2 inhibitors were associated with 73% lower mortality compared to those of DPP-4 inhibitors or users of older agents, while 36% lower total costs against those of GLP-1 agonists. However, there was no statistically significant difference in the risk of lower extremity amputation across medication groups. Our study suggested that SGLT-2 inhibitors is associated with lower mortality compared to DPP 4 inhibitors and lower costs compared to GLP-1 agonists.


Type 2 diabetes, Health care economics, Outcomes research, Adverse effects

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Copyright © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

DOI of Published Version



Chang HY, Chou YY, Tang W, Chang GM, Hsieh CF, Singh S, Tung YC. Association of antidiabetic therapies with lower extremity amputation, mortality and healthcare cost from a nationwide retrospective cohort study in Taiwan. Sci Rep. 2021 Mar 26;11(1):7000. doi: 10.1038/s41598-021-86516-4. PMID: 33772082; PMCID: PMC7997872. Link to article on publisher's site

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Scientific reports

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Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.