Association Between Hospitalization for Heart Failure and Dipeptidyl Peptidase 4 Inhibitors in Patients With Type 2 Diabetes: An Observational Study

Abstract

OBJECTIVETo examine, among patients with type 2 diabetes, the association between hospitalization for heart failure (hHF) and treatment with dipeptidyl peptidase 4 inhibitors (DPP-4is) versus sulfonylureas (SUs), and treatment with saxagliptin versus sitagliptin. RESEARCH DESIGN AND METHODSThis was a retrospective, observational study using a U.S. insurance claims database. Patients initiated treatment between 1 August 2010 and 30 August 2013, and had no use of the comparator treatments in the prior 12 months (baseline). Each comparison consisted of patients matched 1:1 on a propensity score. Time to each outcome was compared between matched groups using Cox models. Analyses were stratified by the presence of baseline cardiovascular disease (CVD). Secondary analyses examined associations between comparator treatments and other selected cardiovascular events. RESULTSAfter matching, the study included 218,556 patients in comparisons of DPP-4i and SU, and 112,888 in comparisons of saxagliptin and sitagliptin. The hazard ratios (HRs) of hHF were as follows: DPP-4i versus SU (reference): HR 0.95 (95% CI 0.78-1.15), P = 0.580 for patients with baseline CVD; HR 0.59 (95% CI 0.38-0.89), P = 0.013 for patients without baseline CVD; saxagliptin versus sitagliptin (reference): HR 0.95 (95% CI 0.70-1.28), P = 0.712 for patients with baseline CVD; HR 0.99 (95% CI 0.56-1.75), P = 0.972 for patients without baseline CVD. Comparisons of the individual secondary and composite cardiovascular outcomes followed a similar pattern. CONCLUSIONSIn patients with type 2 diabetes, there was no association between hHF, or other selected cardiovascular outcomes, and treatment with a DPP-4i relative to SU or treatment with saxagliptin relative to sitagliptin.

Dipeptidyl Peptidase-4 Inhibitors in Chronic Kidney Disease: A Systematic Review of Randomized Clinical Trials

“…However, 2 recent observational studies reported no association between heart failure, other cardiovascular outcomes, and treatment with a DPP-4 inhibitor (saxagliptin and sitagliptin), relative to treatment with sulfonylureas [29,30] . A third trial examining alogliptin found no increased risk of cardiovascular mortality among diabetic patients with moderate or severe renal impairment, and a recent observational study of over 1.5 million patients found no increased risk of hospitalization for heart failure when incretin-based drugs were used [31,32] .…”

Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction

“…NDV, normal diet rats treated with vehicle; NDE, normal diet rats treated with enalapril; NDVil, normal diet rats treated with vildagliptin; NDM, normal diet rats treated with metformin; NDC, normal diet rats treated with combined drugs; HFDV, high-fatfed rats treated with vehicle; HFDE, high-fat-fed rats treated with enalapril; HFDVil, high-fat-fed rats treated with vildagliptin; HFDM, high-fat-fed rats treated with metformin; HFDC, high-fat-fed rats treated with combined drugs. cardiovascular events nor the rate of hospitalization for HF (McInnes et al 2015, Wang et al 2015, Fu et al 2016. However, Suh and colleagues reported otherwise, as they showed that sitagliptin and vildagliptin increased the hospitalization rate for HF after 30 days of medication (Suh et al 2015).…”

Safety and efficacy of linagliptin in patients with type 2 diabetes mellitus and coronary artery disease: Analysis of pooled events from 19 clinical trials

“…A recent retrospective, observational study, using information from a US insurance claims database, found no association between hospitalization for heart failure and treatment with a DPP-4 inhibitor relative to SU therapy, or treatment with saxagliptin relative to sitagliptin (Fu et al, 2016). At present, therefore, it remains unclear whether the observation of an increase in hospitalization for CHF with saxagliptin (Scirica et al, 2013) was an adverse effect of this specific therapy or a chance finding.…”