European Journal of Clinical Pharmacology

, Volume 75, Issue 12, pp 1723–1730 | Cite as

National trends in metformin-based combination therapy of oral hypoglycaemic agents for type 2 diabetes mellitus

  • Jisu Kim
  • Susin Park
  • Hyunsoo Kim
  • Nam Kyung JeEmail author
Pharmacoepidemiology and Prescription



The American Diabetes Association guidelines recommend metformin monotherapy for type 2 diabetes mellitus as an initial agent due to its effectiveness and safety. If the target glycosylated haemoglobin level is not attained within 3 months, add-on therapy is recommended. This study aimed to investigate the prescribing trends of add-on therapy to metformin focusing on factors affecting the selection of second agents using real-world data.


Patients who were undergoing metformin monotherapy for at least 3 months and switched to metformin-based combination therapy were selected. The oral antidiabetic drugs used as add-on therapy were classified into 4 classes: dipeptidyl peptidase-4 inhibitors (DPP4I), sodium glucose cotransporter-2 inhibitors (SGLT2I), sulphonylureas (SU), and thiazolidinediones (TZD). The drug regimen was also classified as older and newer agents. Chi-square test and logistic regression analysis were performed to estimate the influencing factors.


In 2014–2016, the use of DPP4I and SGLT2I increased, whereas the use of SU and TZD decreased. Our results show that the prescription pattern was influenced by the type and location of the institution, specialty of physicians, some comorbidities, and patient characteristics such as age and sex. Newer agents were more commonly used in younger patients. SGLT2I were more preferred in women than in men. Patients with dyslipidaemia showed increased odds of utilising newer agents.


DPP4I were the most commonly utilised agents in metformin-based combination therapy and SGLT2I use is expected to increase more due to their cardioprotective effects. Proper selection of add-on therapy, based on drug-specific effects and patient factors, is necessary.


Diabetes mellitus Antidiabetic drug Add-on therapy 



The Health Insurance Review and Assessment Service (HIRA) National Patient Sample from 2014 to 2016 (HIRA-NPS-2014-0061, HIRA-NPS-2015-0059, HIRA-NPS-2016-0058) was used for this study; however, the results do not concern the Ministry of Health and Welfare or HIRA.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

228_2019_2751_MOESM1_ESM.docx (24 kb)
ESM 1 (DOCX 24 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of PharmacyPusan National UniversityBusanRepublic of Korea

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