Incretin-Based Drugs and the Risk of Congestive Heart Failure

Abstract

OBJECTIVETo determine whether the use of incretin-based drugs, including GLP-1 analogs and dipeptidyl peptidase-4 inhibitors, is associated with an increased risk of congestive heart failure (CHF) among patients with type 2 diabetes. RESEARCH DESIGN AND METHODSThe U.K. Clinical Practice Research Datalink, linked to the Hospital Episode Statistics database, was used to conduct a cohort study with a nested case-control analysis among patients newly prescribed antidiabetic drugs between 1 January 2007 and 31 March 2012 and no prior history of CHF. Case subjects were defined as patients hospitalized for a first CHF and matched with up to 20 control subjects on age, duration of treated diabetes, calendar year, and time since cohort entry. Conditional logistic regression was used to estimate odds ratios (ORs) with corresponding 95% CIs of incident CHF comparing current use of incretin-based drugs with current use of two or more oral antidiabetic drugs. RESULTSThe cohort consisted of 57,737 patients followed for a mean 2.4 years, during which time 1,118 incident cases of hospitalized CHF were identified (incidence rate 8.1/1,000 person-years). Current use of incretin-based drugs was not associated with an increased risk of CHF (adjusted OR 0.85 [95% CI 0.62-1.16]). Secondary analyses revealed no duration-response relationship (P trend = 0.39). CONCLUSIONSIn our population-based study, incretin-based drug use was not associated with an increased risk of CHF among patients with type 2 diabetes. These findings provide some reassurance, but will need to be replicated in other large-scale studies.Incretin-based drugs, which consist of dipeptidyl peptidase-4 (DPP-4) inhibitors and GLP-1 analogs, were first approved by the U.S. Food and Drug Administration in 2006 for the treatment of type 2 diabetes. Both DPP-4 inhibitors and GLP-1 analogs improve glycemic control by increasing plasma levels of endogenous and exogenous GLP-1, respectively. This increase in GLP-1 stimulates insulin secretion and inhibits glucagon secretion (1).The cardiovascular safety of incretin-based drugs is currently under debate. This debate stems from a secondary analysis of the randomized controlled trial SAVOR-TIMI 53, in which saxagliptin was associated with an increased risk of congestive heart failure (CHF) (hazard ratio [HR] 1.27 [95% CI 1.07-1.51]) (2). In contrast, the EXAMINE trial found no association between alogliptin and CHF (HR 1.07 [95% CI 0.79-1.46]) (3). A subsequent meta-analysis of randomized controlled trials found an increased risk of CHF with DPP-4 inhibitors (relative risk 1.16 [95% CI 1.01-1.33]) (4), but these results were driven by those of SAVOR-TIMI 53. Although the safety

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

“…Prior observational studies (12,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) that assessed the association between hHF and either the DPP-4i agents as a class or specific DPP-4i agents (i.e., sitagliptin) have used a wide variety of designs and patient populations with mixed results. Two studies (12,18) identified that DPP-4i treatment is associated with a reduced rate of hHF relative to other oral antihyperglycemic medications, two studies (14,16) suggested a neutral association relative to other oral antihyperglycemic medications and/or insulin, and two studies (19,20) suggested an increased rate of hHF with DPP-4i treatment relative to matched control subjects not otherwise initiating a new antihyperglycemic medication but rather in the midst of treatment with any of a range of potential antihyperglycemic medications.…”

Is the Use of DPP-4 Inhibitors Associated With an Increased Risk for Heart Failure? Lessons From EXAMINE, SAVOR-TIMI 53, and TECOS

“…Several observational studies have attempted to assess the association between the use of DPP-4 inhibitors and hospitalization for HF (25)(26)(27)(28)(29) (Table 1). The studies have generally used propensity score matching, with varying success at matching the groups, and applied a Cox proportional hazards model or a conditional logistic regression to adjust for further confounding.…”

Heart failure in diabetes: effects of anti-hyperglycemic drug therapy

“…Данные крупных регистров, основанных на анализе частоты развития сердечно-сосудистых событий и СН при лечении пациентов с СД2 иДПП-4 в сравнении с другими антидиабетическими препаратами, показали сопоставимую частоту развития сердечно-сосудистых событий и госпитализаций, связанных с СН [37]. Таким образом, вопрос о влиянии иДПП-4 на развитие или те-чение СН на основании имеющихся данных остается открытым.…”