Impact of metformin use on the cardiovascular effects of dipeptidyl peptidase‐4 inhibitors: An analysis of Medicare claims data from 2007 to 2015. Issue 4 (18th December 2018)

• Record Type: Journal Article
• Authors: Crowley, Matthew J.; Gokhale, Mugdha; Pate, Virginia; Stürmer, Til; Buse, John B.
• Is Part Of: Diabetes, obesity & metabolism. Volume 21:Issue 4(2019)
• Page Start: 854
• Page End: 865
• Publication Date: 2018-12-18
• Subjects: cardiovascular disease -- DPP‐4 inhibitor -- metformin -- pharmaco‐epidemiology -- type 2 diabetes; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.13589
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract : Aims: To examine the outcomes of dipeptidyl peptidase‐4 (DPP‐4) inhibitor initiation with and without concurrent metformin treatment. Materials and methods: We identified Medicare enrollees initiating a DPP‐4 inhibitor, a sulphonylurea or a thiazolidinedione. Using propensity‐score‐weighted Poisson models, we evaluated 1‐year cardiovascular (CV) outcome incidence among initiators of DPP‐4 inhibitors versus comparators in subgroups with and without concurrent metformin use, and assessed the interaction between initiation drug and metformin. Outcomes included mortality, non‐fatal myocardial infarction (MI), stroke, and a composite outcome. Results: For the DPP‐4 inhibitor (n = 13 391) versus sulphonylurea (n = 33 206) comparison, rate differences in composite outcome incidence favoured DPP‐4 inhibitors: −2.0/100 person‐years among metformin users (95% confidence interval [CI] −2.7 to −1.3) and − 1.0/100 person‐years (95% CI −1.8 to −0.2) among metformin non‐users. Similar rate difference trends among metformin users and non‐users were seen for mortality (−1.5/100 person‐years [95% CI −2.1 to −0.9] and −0.7/100 person‐years [95% CI −1.4 to 0.0]) and non‐fatal MI (−0.5/100 person‐years [95% CI −0.8, −0.3] and 0.1/100 person‐years [95% CI −0.2 to 0.4]). The interaction between DPP‐4 inhibitor initiation and metformin was statistically significant for non‐fatal MI ( P = 0.008). For the DPP‐4 inhibitor (n = 22 210) versus thiazolidinedione (n = 9517) comparison, rate differences in composite outcome incidence for DPP‐4 inhibitor initiation were −0.6/100 person‐years (95% CI −1.5 to 0.2) among metformin users and 1.0 (95% CI 0.0 to 2.0) among metformin non‐users. Similar rate difference trends among metformin users and non‐users were seen for mortality (−0.5/100 person‐years [95% CI −1.3 to 0.1] and 0.8/100 person‐years [95% CI −0.0 to 1.7]) and non‐fatal MI (−0.1/100 person‐years [95% CI −0.4 to 0.2] and 0.2/100 person‐years [95% CI −0.1 to 0.6]). The interaction between DPP‐4 inhibitor initiation and metformin was statistically significant for the composite outcome ( P = 0.024) and mortality ( P = 0.023). Conclusion: Incidence rate differences in multiple CV outcomes appeared more favourable when DPP‐4 inhibitor initiation occurred in the presence of metformin, suggesting a possible interaction between DPP‐4 inhibitors and metformin.