Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus: Secondary analysis of a randomized clinical trial

Darren K McGuire, Frans Van De Werf, Paul W. Armstrong, Eberhard Standl, Joerg Koglin, Jennifer B. Green, M. Angelyn Bethel, Jan H. Cornel, Renato D. Lopes, Sigrun Halvorsen, Giuseppe Ambrosio, John B. Buse, Robert G. Josse, John M. Lachin, Michael J. Pencina, Jyotsna Garg, Yuliya Lokhnygina, Rury R. Holman, Eric D. Peterson

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

IMPORTANCE: Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP4i) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP4i sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS). OBJECTIVE: To assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes. DESIGN, SETTING, AND PARTICIPANTS: TECOS wasarandomized, double-blind, placebo-controlled study evaluating the CV safety of sitagliptin vs placebo, each added to usual antihyperglycemic therapy and CV care among patients with T2DM and prevalent atherosclerotic vascular disease. The median follow-up was 2.9 years. The setting was 673 sites in 38 countries. Participants included 14 671 patients with T2DM and atherosclerotic vascular disease. The study dates were December 2008 through March 2015. INTERVENTIONS: Patients were randomized to sitagliptin vs placebo added to standard care. MAIN OUTCOMES AND MEASURES: Prespecified secondary analyses compared the effect on hHF, hHF or CV death, and hHF orall-cause death composite outcomes overall and in prespecified subgroups. Supportive analyses included total hHF events (first plus recurrent) and post-hHF death. Meta-analyses evaluated DPP4i effects on hHF and on hHFor CV death. RESULTS: Of 14 671 patients, 7332 were randomized to sitagliptin and 7339 to placebo. Hospitalization for HF occurred in 3.1% (n = 228) and 3.1% (n = 229) of the sitagliptin and placebo groups, respectively (unadjusted hazard ratio, 1.00; 95% CI, 0.83-1.19). There was also no difference in total hHF events between the sitagliptin (n = 345) and placebo (n = 347) groups (unadjusted hazard ratio, 1.00; 95% CI, 0.80-1.25). Post-hHF all-cause death was similar in the sitagliptin and placebo groups (29.8% vs 28.8%, respectively), as was CV death (22.4% vs 23.1%, respectively). No heterogeneity for the effect of sitagliptin on hHF was observed in subgroup analyses across 21 factors (P > .10 for all interactions). Meta-analysis of the hHF results from the 3 reported DPP4i CV outcomes trials revealed moderate heterogeneity (I2 = 44.9, P = .16). CONCLUSIONS AND RELEVANCE: Sitagliptin use does not affect the risk for hHF in T2DM, both overall and among high-risk patient subgroups.

Original languageEnglish (US)
Pages (from-to)126-135
Number of pages10
JournalJAMA Cardiology
Volume1
Issue number2
DOIs
StatePublished - May 1 2016

Fingerprint

Type 2 Diabetes Mellitus
Hospitalization
Randomized Controlled Trials
Heart Failure
Placebos
Dipeptidyl-Peptidase IV Inhibitors
Sitagliptin Phosphate
Vascular Diseases
Meta-Analysis
Cause of Death
Hypoglycemic Agents
Patient Care
Safety

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus : Secondary analysis of a randomized clinical trial. / McGuire, Darren K; Van De Werf, Frans; Armstrong, Paul W.; Standl, Eberhard; Koglin, Joerg; Green, Jennifer B.; Bethel, M. Angelyn; Cornel, Jan H.; Lopes, Renato D.; Halvorsen, Sigrun; Ambrosio, Giuseppe; Buse, John B.; Josse, Robert G.; Lachin, John M.; Pencina, Michael J.; Garg, Jyotsna; Lokhnygina, Yuliya; Holman, Rury R.; Peterson, Eric D.

In: JAMA Cardiology, Vol. 1, No. 2, 01.05.2016, p. 126-135.

Research output: Contribution to journalArticle

McGuire, DK, Van De Werf, F, Armstrong, PW, Standl, E, Koglin, J, Green, JB, Bethel, MA, Cornel, JH, Lopes, RD, Halvorsen, S, Ambrosio, G, Buse, JB, Josse, RG, Lachin, JM, Pencina, MJ, Garg, J, Lokhnygina, Y, Holman, RR & Peterson, ED 2016, 'Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus: Secondary analysis of a randomized clinical trial', JAMA Cardiology, vol. 1, no. 2, pp. 126-135. https://doi.org/10.1001/jamacardio.2016.0103
McGuire, Darren K ; Van De Werf, Frans ; Armstrong, Paul W. ; Standl, Eberhard ; Koglin, Joerg ; Green, Jennifer B. ; Bethel, M. Angelyn ; Cornel, Jan H. ; Lopes, Renato D. ; Halvorsen, Sigrun ; Ambrosio, Giuseppe ; Buse, John B. ; Josse, Robert G. ; Lachin, John M. ; Pencina, Michael J. ; Garg, Jyotsna ; Lokhnygina, Yuliya ; Holman, Rury R. ; Peterson, Eric D. / Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus : Secondary analysis of a randomized clinical trial. In: JAMA Cardiology. 2016 ; Vol. 1, No. 2. pp. 126-135.
@article{872c1d658e1f418fb15397a4a86abf0a,
title = "Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus: Secondary analysis of a randomized clinical trial",
abstract = "IMPORTANCE: Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP4i) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP4i sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS). OBJECTIVE: To assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes. DESIGN, SETTING, AND PARTICIPANTS: TECOS wasarandomized, double-blind, placebo-controlled study evaluating the CV safety of sitagliptin vs placebo, each added to usual antihyperglycemic therapy and CV care among patients with T2DM and prevalent atherosclerotic vascular disease. The median follow-up was 2.9 years. The setting was 673 sites in 38 countries. Participants included 14 671 patients with T2DM and atherosclerotic vascular disease. The study dates were December 2008 through March 2015. INTERVENTIONS: Patients were randomized to sitagliptin vs placebo added to standard care. MAIN OUTCOMES AND MEASURES: Prespecified secondary analyses compared the effect on hHF, hHF or CV death, and hHF orall-cause death composite outcomes overall and in prespecified subgroups. Supportive analyses included total hHF events (first plus recurrent) and post-hHF death. Meta-analyses evaluated DPP4i effects on hHF and on hHFor CV death. RESULTS: Of 14 671 patients, 7332 were randomized to sitagliptin and 7339 to placebo. Hospitalization for HF occurred in 3.1{\%} (n = 228) and 3.1{\%} (n = 229) of the sitagliptin and placebo groups, respectively (unadjusted hazard ratio, 1.00; 95{\%} CI, 0.83-1.19). There was also no difference in total hHF events between the sitagliptin (n = 345) and placebo (n = 347) groups (unadjusted hazard ratio, 1.00; 95{\%} CI, 0.80-1.25). Post-hHF all-cause death was similar in the sitagliptin and placebo groups (29.8{\%} vs 28.8{\%}, respectively), as was CV death (22.4{\%} vs 23.1{\%}, respectively). No heterogeneity for the effect of sitagliptin on hHF was observed in subgroup analyses across 21 factors (P > .10 for all interactions). Meta-analysis of the hHF results from the 3 reported DPP4i CV outcomes trials revealed moderate heterogeneity (I2 = 44.9, P = .16). CONCLUSIONS AND RELEVANCE: Sitagliptin use does not affect the risk for hHF in T2DM, both overall and among high-risk patient subgroups.",
author = "McGuire, {Darren K} and {Van De Werf}, Frans and Armstrong, {Paul W.} and Eberhard Standl and Joerg Koglin and Green, {Jennifer B.} and Bethel, {M. Angelyn} and Cornel, {Jan H.} and Lopes, {Renato D.} and Sigrun Halvorsen and Giuseppe Ambrosio and Buse, {John B.} and Josse, {Robert G.} and Lachin, {John M.} and Pencina, {Michael J.} and Jyotsna Garg and Yuliya Lokhnygina and Holman, {Rury R.} and Peterson, {Eric D.}",
year = "2016",
month = "5",
day = "1",
doi = "10.1001/jamacardio.2016.0103",
language = "English (US)",
volume = "1",
pages = "126--135",
journal = "JAMA Cardiology",
issn = "2380-6583",
publisher = "American Medical Association",
number = "2",

}

TY - JOUR

T1 - Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus

T2 - Secondary analysis of a randomized clinical trial

AU - McGuire, Darren K

AU - Van De Werf, Frans

AU - Armstrong, Paul W.

AU - Standl, Eberhard

AU - Koglin, Joerg

AU - Green, Jennifer B.

AU - Bethel, M. Angelyn

AU - Cornel, Jan H.

AU - Lopes, Renato D.

AU - Halvorsen, Sigrun

AU - Ambrosio, Giuseppe

AU - Buse, John B.

AU - Josse, Robert G.

AU - Lachin, John M.

AU - Pencina, Michael J.

AU - Garg, Jyotsna

AU - Lokhnygina, Yuliya

AU - Holman, Rury R.

AU - Peterson, Eric D.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - IMPORTANCE: Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP4i) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP4i sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS). OBJECTIVE: To assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes. DESIGN, SETTING, AND PARTICIPANTS: TECOS wasarandomized, double-blind, placebo-controlled study evaluating the CV safety of sitagliptin vs placebo, each added to usual antihyperglycemic therapy and CV care among patients with T2DM and prevalent atherosclerotic vascular disease. The median follow-up was 2.9 years. The setting was 673 sites in 38 countries. Participants included 14 671 patients with T2DM and atherosclerotic vascular disease. The study dates were December 2008 through March 2015. INTERVENTIONS: Patients were randomized to sitagliptin vs placebo added to standard care. MAIN OUTCOMES AND MEASURES: Prespecified secondary analyses compared the effect on hHF, hHF or CV death, and hHF orall-cause death composite outcomes overall and in prespecified subgroups. Supportive analyses included total hHF events (first plus recurrent) and post-hHF death. Meta-analyses evaluated DPP4i effects on hHF and on hHFor CV death. RESULTS: Of 14 671 patients, 7332 were randomized to sitagliptin and 7339 to placebo. Hospitalization for HF occurred in 3.1% (n = 228) and 3.1% (n = 229) of the sitagliptin and placebo groups, respectively (unadjusted hazard ratio, 1.00; 95% CI, 0.83-1.19). There was also no difference in total hHF events between the sitagliptin (n = 345) and placebo (n = 347) groups (unadjusted hazard ratio, 1.00; 95% CI, 0.80-1.25). Post-hHF all-cause death was similar in the sitagliptin and placebo groups (29.8% vs 28.8%, respectively), as was CV death (22.4% vs 23.1%, respectively). No heterogeneity for the effect of sitagliptin on hHF was observed in subgroup analyses across 21 factors (P > .10 for all interactions). Meta-analysis of the hHF results from the 3 reported DPP4i CV outcomes trials revealed moderate heterogeneity (I2 = 44.9, P = .16). CONCLUSIONS AND RELEVANCE: Sitagliptin use does not affect the risk for hHF in T2DM, both overall and among high-risk patient subgroups.

AB - IMPORTANCE: Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP4i) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP4i sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS). OBJECTIVE: To assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes. DESIGN, SETTING, AND PARTICIPANTS: TECOS wasarandomized, double-blind, placebo-controlled study evaluating the CV safety of sitagliptin vs placebo, each added to usual antihyperglycemic therapy and CV care among patients with T2DM and prevalent atherosclerotic vascular disease. The median follow-up was 2.9 years. The setting was 673 sites in 38 countries. Participants included 14 671 patients with T2DM and atherosclerotic vascular disease. The study dates were December 2008 through March 2015. INTERVENTIONS: Patients were randomized to sitagliptin vs placebo added to standard care. MAIN OUTCOMES AND MEASURES: Prespecified secondary analyses compared the effect on hHF, hHF or CV death, and hHF orall-cause death composite outcomes overall and in prespecified subgroups. Supportive analyses included total hHF events (first plus recurrent) and post-hHF death. Meta-analyses evaluated DPP4i effects on hHF and on hHFor CV death. RESULTS: Of 14 671 patients, 7332 were randomized to sitagliptin and 7339 to placebo. Hospitalization for HF occurred in 3.1% (n = 228) and 3.1% (n = 229) of the sitagliptin and placebo groups, respectively (unadjusted hazard ratio, 1.00; 95% CI, 0.83-1.19). There was also no difference in total hHF events between the sitagliptin (n = 345) and placebo (n = 347) groups (unadjusted hazard ratio, 1.00; 95% CI, 0.80-1.25). Post-hHF all-cause death was similar in the sitagliptin and placebo groups (29.8% vs 28.8%, respectively), as was CV death (22.4% vs 23.1%, respectively). No heterogeneity for the effect of sitagliptin on hHF was observed in subgroup analyses across 21 factors (P > .10 for all interactions). Meta-analysis of the hHF results from the 3 reported DPP4i CV outcomes trials revealed moderate heterogeneity (I2 = 44.9, P = .16). CONCLUSIONS AND RELEVANCE: Sitagliptin use does not affect the risk for hHF in T2DM, both overall and among high-risk patient subgroups.

UR - http://www.scopus.com/inward/record.url?scp=85021438535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021438535&partnerID=8YFLogxK

U2 - 10.1001/jamacardio.2016.0103

DO - 10.1001/jamacardio.2016.0103

M3 - Article

C2 - 27437883

AN - SCOPUS:85021438535

VL - 1

SP - 126

EP - 135

JO - JAMA Cardiology

JF - JAMA Cardiology

SN - 2380-6583

IS - 2

ER -