Differential Cardiovascular Outcomes after Dipeptidyl Peptidase-4 Inhibitor, Sulfonylurea, and Pioglitazone Therapy, All in Combination with Metformin, for Type 2 Diabetes: A Population-Based Cohort Study

Abstract

Background/ObjectivesData on the comparative effectiveness of oral antidiabetics on cardiovascular outcomes in a clinical practice setting are limited. This study sought to determine whether a differential risk of cardiovascular disease (CVD) exists for the combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor plus metformin versus a sulfonylurea derivative plus metformin or pioglitazone plus metformin.MethodsWe conducted a cohort study of 349,476 patients who received treatment with a DPP-4 inhibitor, sulfonylurea, or pioglitazone plus metformin for type 2 diabetes using the Korean national health insurance claims database. The incidence of total CVD and individual outcomes of myocardial infarction (MI), heart failure (HF), and ischemic stroke (IS) were assessed using the hazard ratios (HRs) estimated from a Cox proportional-hazards model weighted for a propensity score.ResultsDuring follow-up, 3,881 patients developed a CVD, including 428 MIs, 212 HFs, and 1,487 ISs. The adjusted HR with 95% confidence interval (CI) for a sulfonylurea derivative plus metformin compared with a DPP-4 inhibitor plus metformin was 1.20 (1.09-1.32) for total CVD; 1.14 (1.04-1.91) for MI; 1.07 (0.71-1.62) for HF; and 1.51 (1.28-1.79) for IS. The HRs with 95% CI for total CVD, MI, HF, and IS for pioglitazone plus metformin were 0.89 (0.81-0.99), 1.05 (0.76-1.46), 4.81 (3.53-6.56), and 0.81 (0.67-0.99), respectively.ConclusionsCompared with a DPP-4 inhibitor plus metformin, treatment with a sulfonylurea drug plus metformin was associated with increased risks of total CVD, MI, and IS, whereas the use of pioglitazone plus metformin was associated with decreased total CVD and IS risks.

Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies

“…Effects on hospital admission for heart failure All five trials 9 evidence from observational studies Of 12 observational studies, four [109][110][111][112] reported heart failure, and eight 13-17 113-115 reported hospital admission for heart failure; nine 13-15 109-111 [113][114][115] were cohort studies and the other three 16 17 112 were nested case-control studies (fig 1). Observational studies reporting heart failure Of the four studies reporting heart failure, two prospective cohort studies 109 (table 4 and table 5).…”

Comparative risk for cardiovascular diseases of dipeptidyl peptidase-4 inhibitors vs. sulfonylureas in combination with metformin: Results of a two-phase study

“…Furthermore, the comparability with the study of Gallwitz et al is limited since linagliptin is not sold in Germany and it is unclear whether the results for linagliptin hold true for all DPP-4 inhibitors. The only study that included heart failure as part of the cardiovascular event was the one conducted by Seong et al (2015) based on Korean health insurance data. The authors reported a significantly increased risk of 20% for a cardiovascular event in patients with a combination therapy of metformin and sulfonylureas compared to DPP-4 inhibitors, which is similar to the results of our study.…”

“…However, occurrence of heart failure was not investigated in these studies. A recently conducted observational study based on data of Korean national health insurances observed an increased risk of total cardiovascular disease but not of heart failure for a combination of metformin and sulfonylureas compared to metformin and DPP-4 inhibitors (Seong et al, 2015).…”

Insulinosensibilisateurs (metformine/glitazones) : niveau de preuve et controverse

“…Dans ces études, la pioglitazone s'est révélée être associée à un meilleur pronostic CV (hormis le risque d'insuffisance cardiaque qui était accru) que la metformine [18] ou qu'un sulfamide hypoglycémiant chez des patients par ailleurs déjà traités par metformine [31]. De plus, quelques études observationnelles ont comparé le devenir de patients DT2 traités par glitazones, et ont montré que la pioglitazone était associée à un meilleur pronostic que la rosiglitazone [18,32].…”