National trends in metformin-based combination therapy of oral hypoglycaemic agents for type 2 diabetes mellitus
- 211 Downloads
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.
KeywordsDiabetes 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.
- 1.Alam U, Asghar O, Azmi S, Malik RA (2014) General aspects of diabetes mellitus. Handb Clin Neurol 126:211–222. https://doi.org/10.1016/b978-0-444-53480-4.00015-1 CrossRefPubMedGoogle Scholar
- 2.Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE (2017) IDF diabetes atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 128:40–50. https://doi.org/10.1016/j.diabres.2017.03.024 CrossRefGoogle Scholar
- 4.(2018) 8. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2018. Diabetes Care 41 (Suppl 1): S73-s85 DOI https://doi.org/10.2337/dc18-S008
- 5.Ko SH, Kim SR, Kim DJ, Oh SJ, Lee HJ, Shim KH, Woo MH, Kim JY, Kim NH, Kim JT, Kim CH, Kim HJ, Jeong IK, Hong EK, Cho JH, Mok JO, Yoon KH (2011) 2011 clinical practice guidelines for type 2 diabetes in Korea. Diabetes Metab J 35(5):431–436. https://doi.org/10.4093/dmj.2011.35.5.431 CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Ko SH, Han K, Lee YH, Noh J, Park CY, Kim DJ, Jung CH, Lee KU, Ko KS (2018) Past and current status of adult type 2 diabetes mellitus management in Korea: a National Health Insurance Service database analysis. Diabetes Metab J 42(2):93–100. https://doi.org/10.4093/dmj.2018.42.2.93 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Baviera M, Monesi L, Marzona I, Avanzini F, Monesi G, Nobili A, Tettamanti M, Riva E, Cortesi L, Bortolotti A, Fortino I, Merlino L, Fontana G, Roncaglioni MC (2011) Trends in drug prescriptions to diabetic patients from 2000 to 2008 in Italy’s Lombardy Region: a large population-based study. Diabetes Res Clin Pract 93(1):123–130. https://doi.org/10.1016/j.diabres.2011.05.004 CrossRefPubMedGoogle Scholar
- 14.Ko SH, Kim DJ, Park JH, Park CY, Jung CH, Kwon HS, Park JY, Song KH, Han K, Lee KU, Ko KS (2016) Trends of antidiabetic drug use in adult type 2 diabetes in Korea in 2002-2013: nationwide population-based cohort study. Medicine 95(27):e4018. https://doi.org/10.1097/md.0000000000004018 CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Mishriky BM, Cummings DM, Tanenberg RJ (2015) The efficacy and safety of DPP4 inhibitors compared to sulfonylureas as add-on therapy to metformin in patients with type 2 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract 109(2):378–388. https://doi.org/10.1016/j.diabres.2015.05.025 CrossRefPubMedGoogle Scholar
- 17.Palmer SC, Mavridis D, Nicolucci A, Johnson DW, Tonelli M, Craig JC, Maggo J, Gray V, De Berardis G, Ruospo M, Natale P, Saglimbene V, Badve SV, Cho Y, Nadeau-Fredette AC, Burke M, Faruque L, Lloyd A, Ahmad N, Liu Y, Tiv S, Wiebe N, Strippoli GF (2016) Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis. Jama 316(3):313–324. https://doi.org/10.1001/jama.2016.9400 CrossRefPubMedGoogle Scholar
- 21.Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, Chu Y, Iyoha E, Segal JB, Bolen S (2016) Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 164(11):740–751. https://doi.org/10.7326/m15-2650 CrossRefPubMedGoogle Scholar
- 23.Nauck MA, Del Prato S, Meier JJ, Duran-Garcia S, Rohwedder K, Elze M, Parikh SJ (2011) Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 34(9):2015–2022. https://doi.org/10.2337/dc11-0606 CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Cefalu WT, Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J, Balis DA, Canovatchel W, Meininger G (2013) Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382(9896):941–950. https://doi.org/10.1016/s0140-6736(13)60683-2 CrossRefGoogle Scholar
- 29.Fukuda-Tsuru S, Anabuki J, Abe Y, Yoshida K, Ishii S (2012) A novel, potent, and long-lasting dipeptidyl peptidase-4 inhibitor, teneligliptin, improves postprandial hyperglycemia and dyslipidemia after single and repeated administrations. Eur J Pharmacol 696(1–3):194–202. https://doi.org/10.1016/j.ejphar.2012.09.024 CrossRefPubMedGoogle Scholar
- 30.Masuda D, Kobayashi T, Sairyou M, Hanada H, Ohama T, Koseki M, Nishida M, Maeda N, Kihara S, Minami T, Yanagi K, Sakata Y, Yamashita S (2018) Effects of a dipeptidyl peptidase 4 inhibitor sitagliptin on glycemic control and lipoprotein metabolism in patients with type 2 diabetes mellitus (GLORIA trial). J Atheroscler Thromb 25(6):512–520. https://doi.org/10.5551/jat.41343 CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Yale JF (2005) Oral antihyperglycemic agents and renal disease: new agents, new concepts. J Am Soc Nephrol 16 Suppl 1: S7–10Google Scholar
- 35.Kalra S, Aamir AH, Raza A, Das AK, Azad Khan AK, Shrestha D, Qureshi MF, Md F, Pathan MF, Jawad F, Bhattarai J, Tandon N, Somasundaram N, Katulanda P, Sahay R, Dhungel S, Bajaj S, Chowdhury S, Ghosh S, Madhu SV, Ahmed T, Bulughapitiya U (2015) lace of sulfonylureas in the management of type 2 diabetes mellitus in South Asia: a consensus statement. Indian J Endocrinol Metab 19(5):577–596. https://doi.org/10.4103/2230-8210.163171 CrossRefGoogle Scholar
- 36.(2018) 9. Cardiovascular disease and risk management: standards of medical care in diabetes-2018. Diabetes Care 41 (Suppl 1): S86-s104 DOI https://doi.org/10.2337/dc18-S009