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Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study.
Cardiovasc Diabetol. 2018 01 24; 17(1):20.CD

Abstract

OBJECTIVE

Metformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort.

METHODS

T2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database. Five classes of ADAs, including sulphonylureas (SU), glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The reference group was the SU added to metformin. Patients were excluded if aged < 20 years, had a history of stroke or acute coronary syndrome (ACS), or were receiving insulin treatment. The primary outcomes included any major adverse cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and death. A Cox regression model was used to estimate the hazard ratio (HR) for MACE.

RESULTS

A total of 26,742 patients receiving their add-on drug to metformin of either SU (n = 24,277), glinides (n = 962), TZD (n = 581), AGI (n = 808), or DPP-4I (n = 114) were analyzed. After a mean follow-up duration of 6.6 ± 3.4 years, a total of 4775 MACEs occurred. Compared with the SU+metformin group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50-0.88, p = 0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59-0.94, p = 0.01) groups showed a significantly lower risk of MACE.

CONCLUSION

Both TZD and AGI, when used as an add-on drug to metformin were associated with lower MACE risk when compared with SU added to metformin in this retrospective cohort study. Trial registration CE13152B-3. Registered 7 Mar, 2013, retrospectively registered.

Authors+Show Affiliations

Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan. Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan.Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan. Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan.Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan. Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan. Department of Internal Medicine, Chiayi Branch, Taichung Veterans General Hospital, Chiayi, Taiwan. Department of Financial and Computational Mathematics, Providence University, Taichung, Taiwan.Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan. ychsieh@vghtc.gov.tw. Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan. ychsieh@vghtc.gov.tw. Department of Internal Medicine, Chiayi Branch, Taichung Veterans General Hospital, Chiayi, Taiwan. ychsieh@vghtc.gov.tw. Department of Financial and Computational Mathematics, Providence University, Taichung, Taiwan. ychsieh@vghtc.gov.tw.Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.Department of Internal Medicine, Hsinchu Branch, Taipei Veterans General Hospital, Hsinchu, Taiwan. Department of Nutrition, Hung-Kuang University, Taichung, Taiwan.Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan. Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan.Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan. Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan.Department of Financial and Computational Mathematics, Providence University, Taichung, Taiwan.Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan. Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan.Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan. Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan.

Pub Type(s)

Comparative Study
Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29368615

Citation

Chan, Cheng-Wei, et al. "Glitazones and Alpha-glucosidase Inhibitors as the Second-line Oral Anti-diabetic Agents Added to Metformin Reduce Cardiovascular Risk in Type 2 Diabetes Patients: a Nationwide Cohort Observational Study." Cardiovascular Diabetology, vol. 17, no. 1, 2018, p. 20.
Chan CW, Yu CL, Lin JC, et al. Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study. Cardiovasc Diabetol. 2018;17(1):20.
Chan, C. W., Yu, C. L., Lin, J. C., Hsieh, Y. C., Lin, C. C., Hung, C. Y., Li, C. H., Liao, Y. C., Lo, C. P., Huang, J. L., Lin, C. H., & Wu, T. J. (2018). Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study. Cardiovascular Diabetology, 17(1), 20. https://doi.org/10.1186/s12933-018-0663-6
Chan CW, et al. Glitazones and Alpha-glucosidase Inhibitors as the Second-line Oral Anti-diabetic Agents Added to Metformin Reduce Cardiovascular Risk in Type 2 Diabetes Patients: a Nationwide Cohort Observational Study. Cardiovasc Diabetol. 2018 01 24;17(1):20. PubMed PMID: 29368615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study. AU - Chan,Cheng-Wei, AU - Yu,Chu-Leng, AU - Lin,Jiunn-Cherng, AU - Hsieh,Yu-Cheng, AU - Lin,Che-Chen, AU - Hung,Chen-Ying, AU - Li,Cheng-Hung, AU - Liao,Ying-Chieh, AU - Lo,Chu-Pin, AU - Huang,Jin-Long, AU - Lin,Ching-Heng, AU - Wu,Tsu-Juey, Y1 - 2018/01/24/ PY - 2017/10/31/received PY - 2018/01/15/accepted PY - 2018/1/26/entrez PY - 2018/1/26/pubmed PY - 2019/1/29/medline KW - Anti-diabetic agent KW - Cardiovascular risk KW - Metformin KW - Type 2 diabetes SP - 20 EP - 20 JF - Cardiovascular diabetology JO - Cardiovasc Diabetol VL - 17 IS - 1 N2 - OBJECTIVE: Metformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort. METHODS: T2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database. Five classes of ADAs, including sulphonylureas (SU), glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The reference group was the SU added to metformin. Patients were excluded if aged < 20 years, had a history of stroke or acute coronary syndrome (ACS), or were receiving insulin treatment. The primary outcomes included any major adverse cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and death. A Cox regression model was used to estimate the hazard ratio (HR) for MACE. RESULTS: A total of 26,742 patients receiving their add-on drug to metformin of either SU (n = 24,277), glinides (n = 962), TZD (n = 581), AGI (n = 808), or DPP-4I (n = 114) were analyzed. After a mean follow-up duration of 6.6 ± 3.4 years, a total of 4775 MACEs occurred. Compared with the SU+metformin group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50-0.88, p = 0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59-0.94, p = 0.01) groups showed a significantly lower risk of MACE. CONCLUSION: Both TZD and AGI, when used as an add-on drug to metformin were associated with lower MACE risk when compared with SU added to metformin in this retrospective cohort study. Trial registration CE13152B-3. Registered 7 Mar, 2013, retrospectively registered. SN - 1475-2840 UR - https://www.unboundmedicine.com/medline/citation/29368615/Glitazones_and_alpha_glucosidase_inhibitors_as_the_second_line_oral_anti_diabetic_agents_added_to_metformin_reduce_cardiovascular_risk_in_Type_2_diabetes_patients:_a_nationwide_cohort_observational_study_ L2 - https://cardiab.biomedcentral.com/articles/10.1186/s12933-018-0663-6 DB - PRIME DP - Unbound Medicine ER -