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Observational Study
, 19 (7), 970-978

No Increased Risk of Cardiovascular Events in Older Adults Initiating Dipeptidyl peptidase-4 Inhibitors vs Therapeutic Alternatives

Affiliations
Observational Study

No Increased Risk of Cardiovascular Events in Older Adults Initiating Dipeptidyl peptidase-4 Inhibitors vs Therapeutic Alternatives

Mugdha Gokhale et al. Diabetes Obes Metab.

Abstract

Aim: To compare the cardiovascular (CV) risk associated with dipeptidyl peptidase-4 (DPP-4) inhibitors relative to sulphonylureas (SUs) and thiazolidinediones (TZDs).

Methods: During 2007 to 2013, using Medicare data for beneficiaries aged >65 years, we identified the following 2 cohorts of new-users, who had not been exposed to the drugs being compared in the 6 months before initiation: (1) DPP-4 inhibitor vs SU initiators and (2) DPP-4 inhibitor vs TZD initiators. Using propensity-score-adjusted Cox models accounting for competing risk by death, we estimated the hazard ratios (HRs), risk differences and 95% confidence intervals (CIs) for myocardial infarction (MI), stroke, hospitalization for heart failure (HF), and a combined outcome (MI, stroke, all-cause mortality).

Results: In the DPP-4 inhibitor vs SU comparison, there were 30 130 DPP-4 inhibitor initiators and 68 382 SU initiators. Their mean age was 75 years, 41% were men and 55% had a baseline CV condition. The HR for the composite outcome was 0.75 (95% CI 0.72-0.79) over a median treatment duration of 1 year, but the 1-year risks of MI were 1.00 (95% CI 0.89-1.12) and 1.47 (95% CI 1.38-1.56) per 100 patients for DPP-4 inhibitors and SUs, respectively, and the corresponding stroke risks were 0.98 (95% CI 0.87-1.10) and 1.09 (95% CI 1.01-1.17). For the DPP-4 inhibitor vs TZD comparison, there were 20 596 DPP-4 inhibitor initiators and 13 526 TZD initiators without previous HF. Their mean age was 74 years, 42% were men and 30% had a baseline CV event. The composite outcome HR was 0.94 (95% CI 0.86-1.02) over a median treatment duration of 1 year. The 1-year risk for MI was ~0.90 and for stroke it was ~0.80 per 100 patients in both DPP-4 inhibitor and TZD initiators.

Conclusion: Although limited by the short treatment period, the present study suggests there is no increased short-term risk of MI, stroke or HF with DPP-4 inhibitors vs SUs/TZDs.

Keywords: DPP-4 inhibitor; antidiabetic drug; database research; incretins; observational study; pharmaco-epidemiology.

Conflict of interest statement

Conflict of interest/disclosures:

M.G. was a doctoral student at University of North Carolina during the conduct of this study. She is now a full time employee of GlaxoSmithKline. Dr. Buse reports grants, non-financial support and other from Eli Lilly, grants, non-financial support and other from Bristol-Myers Squibb, grants, non-financial support and other from GI Dynamics, non-financial support and other from Elcylex, grants, non-financial support and other from Merck, non-financial support and other from Metavention, non-financial support and other from vTv Pharma, grants, personal fees, non-financial support and other from PhaseBio, grants, non-financial support and other from AstraZeneca, non-financial support and other from Dance Biopharm, non-financial support and other from Quest, grants from Medtronic Minimed, grants, non-financial support and other from Sanofi, grants from Tolerex, grants from Osiris, grants from Halozyme, grants from Johnson & Johnson, grants from Andromeda, grants from Boehringer-Ingelheim, grants from GlaxoSmithKline, grants from Astellas, grants from MacroGenics, grants from Intarcia Therapeutics, grants, non-financial support and other from Lexicon, grants from Scion NeuroStim, grants, non-financial support and other from Novo Nordisk, grants, non-financial support and other from Orexigen, grants, non-financial support and other from Takeda, non-financial support and other from Adocia, outside the submitted work; and I am or have been a member of a variety of non-profit boards: American Diabetes Association, DiabetesSisters, Taking Control of Your Diabetes, AstraZeneca Healthcare Foundation, Bristol-Myers Squib Together on Diabetes Foundation, the National Diabetes Education Program. T.S. receives investigator-initiated research funding and support as Principal Investigator (R01 AG023178) from the National Institute on Aging (NIA), and as Co-Investigator (R01 CA174453; R01 HL118255, R21-HD080214), National Institutes of Health (NIH). He also receives salary support as Director of the Comparative Effectiveness Research (CER) Strategic Initiative, NC TraCS Institute, UNC Clinical and Translational Science Award (UL1TR001111) and as Director of the Center for Pharmacoepidemiology (current members: GlaxoSmithKline, UCB BioSciences, Merck) and research support from pharmaceutical companies (Amgen, AstraZeneca) to the Department of Epidemiology, University of North Carolina at Chapel Hill. Dr. Stürmer does not accept personal compensation of any kind from any pharmaceutical company. He owns stock in Novartis, Roche, BASF, AstraZeneca, Johnsen & Johnsen, and Novo Nordisk. Dr. Lund receives research support from the UNC Oncology Clinical Translational Research Training Program (K12 CA120780), as well as through a Research Starter Award from the PhRMA Foundation to the UNC Department of Epidemiology. M.J.F. receives investigator-initiated research funding and support as Principal Investigator from the National Institutes of Health (NIH), National Heart Lung and Blood Institute (NHLBI, R01 HL118255); as a Co-Investigator from the NIH National Institute on Aging (NIA, R01 AG023178), the NIH National Center for Advancing Translational Sciences (NCATS, 1UL1TR001111), AstraZeneca, and the Patient Centered Outcomes Research Institute (PCORI, 1IP2PI000075). Dr. Jonsson Funk does not accept personal compensation of any kind from any pharmaceutical company, though she receives salary support from the Center for Pharmacoepidemiology in the Department of Epidemiology, Gillings School of Global Public Health (current members: GlaxoSmithKline, UCB BioSciences, Merck).

Figures

Figure 1
Figure 1. Weighted cumulative incidence for the composite outcome (non-fatal myocardial infarction, stroke and all-cause mortality)
(A) Dipeptidyl peptidase-4 inhibitors (DPP-4i) versus sulfonylureas (SU) (B) Dipeptidyl peptidase-4 inhibitors (DPP-4i) versus thiazolidinediones (TZD)
Figure 2
Figure 2. Weighted cumulative incidence for non-fatal myocardial infarction (MI) and stroke: DPP-4i versus SU and DPP-4i versus TZD
DPP-4i - dipeptidyl peptidase-4 inhibitors ; SU – sulfonylureas; TZD - thiazolidinediones

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