Effects on clinical outcomes of adding dipeptidyl peptidase-4 inhibitors versus sulfonylureas to metformin therapy in patients with type 2 diabetes mellitus

Shuo Ming Ou, Chia Jen Shih, Pei Wen Chao, Hsi Chu, Shu Chen Kuo, Yi Jung Lee, Shuu Jiun Wang, Chih Yu Yang, Chih Ching Lin, Tzeng Ji Chen, Der Cherng Tarng, Szu Yuan Li, Yung Tai Chen

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)663-672
Number of pages10
JournalAnnals of Internal Medicine
Volume163
Issue number9
DOIs
Publication statusPublished - Nov 3 2015

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Dipeptidyl-Peptidase IV Inhibitors
Metformin
Type 2 Diabetes Mellitus
Hypoglycemia
Heart Failure
Stroke
Taiwan
Therapeutics
Cause of Death
Hospitalization
Myocardial Infarction
Propensity Score
National Health Programs
Proportional Hazards Models
Observational Studies
Databases
Mortality
Research

ASJC Scopus subject areas

  • Internal Medicine

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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. / Ou, Shuo Ming; Shih, Chia Jen; Chao, Pei Wen; Chu, Hsi; Kuo, Shu Chen; Lee, Yi Jung; Wang, Shuu Jiun; Yang, Chih Yu; Lin, Chih Ching; Chen, Tzeng Ji; Tarng, Der Cherng; Li, Szu Yuan; Chen, Yung Tai.

In: Annals of Internal Medicine, Vol. 163, No. 9, 03.11.2015, p. 663-672.

Research output: Contribution to journalArticle

Ou, SM, Shih, CJ, Chao, PW, Chu, H, Kuo, SC, Lee, YJ, Wang, SJ, Yang, CY, Lin, CC, Chen, TJ, Tarng, DC, Li, SY & Chen, YT 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, vol. 163, no. 9, pp. 663-672. https://doi.org/10.7326/M15-0308
Ou, Shuo Ming ; Shih, Chia Jen ; Chao, Pei Wen ; Chu, Hsi ; Kuo, Shu Chen ; Lee, Yi Jung ; Wang, Shuu Jiun ; Yang, Chih Yu ; Lin, Chih Ching ; Chen, Tzeng Ji ; Tarng, Der Cherng ; Li, Szu Yuan ; Chen, Yung Tai. / Effects on clinical outcomes of adding dipeptidyl peptidase-4 inhibitors versus sulfonylureas to metformin therapy in patients with type 2 diabetes mellitus. In: Annals of Internal Medicine. 2015 ; Vol. 163, No. 9. pp. 663-672.
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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.",
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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

PY - 2015/11/3

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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.

AB - 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.

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