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Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus.
Ann Intern Med. 2015 Nov 03; 163(9):663-72.AIM

Abstract

BACKGROUND

Recent studies concluded that dipeptidyl peptidase-4 (DPP-4) inhibitors provide glycemic control but also raised concerns about the risk for heart failure in patients with type 2 diabetes mellitus (T2DM). However, large-scale studies of the effects on cardiovascular outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy remain scarce.

OBJECTIVE

To compare clinical outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy in patients with T2DM.

DESIGN

Nationwide study using Taiwan's National Health Insurance Research Database.

SETTING

Taiwan.

PATIENTS

All patients with T2DM aged 20 years or older between 2009 and 2012. A total of 10,089 propensity score-matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined.

MEASUREMENTS

Cox models with exposure to sulfonylureas and DPP-4 inhibitors included as time-varying covariates were used to compare outcomes. The following outcomes were considered: all-cause mortality, major adverse cardiovascular events (MACEs) (including ischemic stroke and myocardial infarction), hospitalization for heart failure, and hypoglycemia. Patients were followed until death or 31 December 2013.

RESULTS

DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure.

LIMITATION

Observational study design.

CONCLUSION

Compared with sulfonylureas, DPP-4 inhibitors were associated with lower risks for all-cause death, MACEs, ischemic stroke, and hypoglycemia when used as add-ons to metformin therapy.

PRIMARY FUNDING SOURCE

None.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

26457538

Citation

Ou, Shuo-Ming, et al. "Effects On Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus." Annals of Internal Medicine, vol. 163, no. 9, 2015, pp. 663-72.
Ou SM, Shih CJ, Chao PW, et al. Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus. Ann Intern Med. 2015;163(9):663-72.
Ou, S. M., Shih, C. J., Chao, P. W., Chu, H., Kuo, S. C., Lee, Y. J., Wang, S. J., Yang, C. Y., Lin, C. C., Chen, T. J., Tarng, D. C., Li, S. Y., & Chen, Y. T. (2015). Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus. Annals of Internal Medicine, 163(9), 663-72. https://doi.org/10.7326/M15-0308
Ou SM, et al. Effects On Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus. Ann Intern Med. 2015 Nov 3;163(9):663-72. PubMed PMID: 26457538.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus. AU - Ou,Shuo-Ming, AU - Shih,Chia-Jen, AU - Chao,Pei-Wen, AU - Chu,Hsi, AU - Kuo,Shu-Chen, AU - Lee,Yi-Jung, AU - Wang,Shuu-Jiun, AU - Yang,Chih-Yu, AU - Lin,Chih-Ching, AU - Chen,Tzeng-Ji, AU - Tarng,Der-Cherng, AU - Li,Szu-Yuan, AU - Chen,Yung-Tai, Y1 - 2015/10/13/ PY - 2015/10/13/entrez PY - 2015/10/13/pubmed PY - 2016/2/19/medline SP - 663 EP - 72 JF - Annals of internal medicine JO - Ann Intern Med VL - 163 IS - 9 N2 - BACKGROUND: Recent studies concluded that dipeptidyl peptidase-4 (DPP-4) inhibitors provide glycemic control but also raised concerns about the risk for heart failure in patients with type 2 diabetes mellitus (T2DM). However, large-scale studies of the effects on cardiovascular outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy remain scarce. OBJECTIVE: To compare clinical outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy in patients with T2DM. DESIGN: Nationwide study using Taiwan's National Health Insurance Research Database. SETTING: Taiwan. PATIENTS: All patients with T2DM aged 20 years or older between 2009 and 2012. A total of 10,089 propensity score-matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined. MEASUREMENTS: Cox models with exposure to sulfonylureas and DPP-4 inhibitors included as time-varying covariates were used to compare outcomes. The following outcomes were considered: all-cause mortality, major adverse cardiovascular events (MACEs) (including ischemic stroke and myocardial infarction), hospitalization for heart failure, and hypoglycemia. Patients were followed until death or 31 December 2013. RESULTS: DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure. LIMITATION: Observational study design. CONCLUSION: Compared with sulfonylureas, DPP-4 inhibitors were associated with lower risks for all-cause death, MACEs, ischemic stroke, and hypoglycemia when used as add-ons to metformin therapy. PRIMARY FUNDING SOURCE: None. SN - 1539-3704 UR - https://www.unboundmedicine.com/medline/citation/26457538/Effects_on_Clinical_Outcomes_of_Adding_Dipeptidyl_Peptidase_4_Inhibitors_Versus_Sulfonylureas_to_Metformin_Therapy_in_Patients_With_Type_2_Diabetes_Mellitus_ L2 - https://www.acpjournals.org/doi/10.7326/M15-0308?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -