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Cardiovascular risks associated with second-line oral antidiabetic agents added to metformin in patients with Type 2 diabetes: a nationwide cohort study.
Diabet Med. 2015 Nov; 32(11):1460-9.DM

Abstract

AIM

To compare the cardiovascular risks associated with second-line oral antidiabetic agents added to initial metformin therapy in a large nationwide observational study.

METHODS

We conducted a nationwide retrospective cohort study using the Taiwan National Health Insurance database. A total of 36 118 users of different add-on oral antidiabetic agents (sulphonylureas, glinides, pioglitazone, α-glucosidase inhibitors and dipeptidyl peptidase-4 inhibitors) after initial metformin therapy were included in the analysis. The reference group was sulphonylureas added to metformin, the most commonly used combination regimen. The main outcomes of interest were hospitalizations for any cardiovascular event including acute myocardial infarction, congestive heart failure and ischaemic stroke. In the main analysis, all patients were followed within their initiation groups until the study end, disregarding any changes in treatment status over time.

RESULTS

In intention-to-treat analyses, there was no difference in the risk of any cardiovascular event among the add-on combination treatment groups, but significantly lower risks of acute myocardial infarction were found for the glinides plus metformin treatment group (crude hazard ratio 0.52, adjusted hazard ratio 0.39; 95% CI 0.20-0.75) and for the α-glucosidase inhibitors plus metformin treatment group (crude hazard ratio 0.63, adjusted hazard ratio 0.54; 95% CI 0.31-0.95). No difference in risk of congestive heart failure or ischaemic stroke risk was found among the combination treatment groups. In secondary as-treated analyses, similar but less significant associations were found as compared with the primary intention-to-treat analyses for all treatment groups.

CONCLUSION

There were no differences in overall cardiovascular risks among several add-on second-line oral antidiabetic agents; however, glinide plus metformin and α-glucosidase inhibitors plus metformin combination therapies might be associated with lower risks of acute myocardial infarction.

Authors+Show Affiliations

Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. Department of Internal Medicine, National Taiwan University Hospital HsinChu branch, HsinChu, Taiwan.Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. Cardiovascular Center, National Taiwan University Hospital Yun-Lin Branch, Dou-Liou City, Yun-Lin County, Taiwan.Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Pub Type(s)

Comparative Study
Journal Article
Observational Study

Language

eng

PubMed ID

25970814

Citation

Chang, Y-C, et al. "Cardiovascular Risks Associated With Second-line Oral Antidiabetic Agents Added to Metformin in Patients With Type 2 Diabetes: a Nationwide Cohort Study." Diabetic Medicine : a Journal of the British Diabetic Association, vol. 32, no. 11, 2015, pp. 1460-9.
Chang YC, Chuang LM, Lin JW, et al. Cardiovascular risks associated with second-line oral antidiabetic agents added to metformin in patients with Type 2 diabetes: a nationwide cohort study. Diabet Med. 2015;32(11):1460-9.
Chang, Y. C., Chuang, L. M., Lin, J. W., Chen, S. T., Lai, M. S., & Chang, C. H. (2015). Cardiovascular risks associated with second-line oral antidiabetic agents added to metformin in patients with Type 2 diabetes: a nationwide cohort study. Diabetic Medicine : a Journal of the British Diabetic Association, 32(11), 1460-9. https://doi.org/10.1111/dme.12800
Chang YC, et al. Cardiovascular Risks Associated With Second-line Oral Antidiabetic Agents Added to Metformin in Patients With Type 2 Diabetes: a Nationwide Cohort Study. Diabet Med. 2015;32(11):1460-9. PubMed PMID: 25970814.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiovascular risks associated with second-line oral antidiabetic agents added to metformin in patients with Type 2 diabetes: a nationwide cohort study. AU - Chang,Y-C, AU - Chuang,L-M, AU - Lin,J-W, AU - Chen,S-T, AU - Lai,M-S, AU - Chang,C-H, Y1 - 2015/05/28/ PY - 2015/05/08/accepted PY - 2015/5/14/entrez PY - 2015/5/15/pubmed PY - 2016/8/3/medline SP - 1460 EP - 9 JF - Diabetic medicine : a journal of the British Diabetic Association JO - Diabet Med VL - 32 IS - 11 N2 - AIM: To compare the cardiovascular risks associated with second-line oral antidiabetic agents added to initial metformin therapy in a large nationwide observational study. METHODS: We conducted a nationwide retrospective cohort study using the Taiwan National Health Insurance database. A total of 36 118 users of different add-on oral antidiabetic agents (sulphonylureas, glinides, pioglitazone, α-glucosidase inhibitors and dipeptidyl peptidase-4 inhibitors) after initial metformin therapy were included in the analysis. The reference group was sulphonylureas added to metformin, the most commonly used combination regimen. The main outcomes of interest were hospitalizations for any cardiovascular event including acute myocardial infarction, congestive heart failure and ischaemic stroke. In the main analysis, all patients were followed within their initiation groups until the study end, disregarding any changes in treatment status over time. RESULTS: In intention-to-treat analyses, there was no difference in the risk of any cardiovascular event among the add-on combination treatment groups, but significantly lower risks of acute myocardial infarction were found for the glinides plus metformin treatment group (crude hazard ratio 0.52, adjusted hazard ratio 0.39; 95% CI 0.20-0.75) and for the α-glucosidase inhibitors plus metformin treatment group (crude hazard ratio 0.63, adjusted hazard ratio 0.54; 95% CI 0.31-0.95). No difference in risk of congestive heart failure or ischaemic stroke risk was found among the combination treatment groups. In secondary as-treated analyses, similar but less significant associations were found as compared with the primary intention-to-treat analyses for all treatment groups. CONCLUSION: There were no differences in overall cardiovascular risks among several add-on second-line oral antidiabetic agents; however, glinide plus metformin and α-glucosidase inhibitors plus metformin combination therapies might be associated with lower risks of acute myocardial infarction. SN - 1464-5491 UR - https://www.unboundmedicine.com/medline/citation/25970814/Cardiovascular_risks_associated_with_second_line_oral_antidiabetic_agents_added_to_metformin_in_patients_with_Type_2_diabetes:_a_nationwide_cohort_study_ L2 - https://doi.org/10.1111/dme.12800 DB - PRIME DP - Unbound Medicine ER -