Dipeptidyl peptidase-4 inhibitors reduced long-term cardiovascular risk in diabetic patients after percutaneous coronary intervention via insulin-like growth factor-1 axis

• Published in: Scientific reports 2022-03, Vol.12 (1), p.5129-5129, Article 5129
• Main Authors: Chikata, Yuichi, Iwata, Hiroshi, Miyosawa, Katsutoshi, Koike, Takuma, Yasuda, Hidetoshi, Funamizu, Takehiro, Doi, Shinichiro, Endo, Hirohisa, Wada, Hideki, Naito, Ryo, Ogita, Manabu, Dohi, Tomotaka, Kasai, Takatoshi, Isoda, Kikuo, Okazaki, Shinya, Miyauchi, Katsumi, Minamino, Tohru
• Format: Article
• Language: English
• Subjects: 692/4019; 692/53; Angioplasty; Antidiabetics; Body weight; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cerebral infarction; Clinical trials; Coronary artery; Death; Diabetes; Diabetes Mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Health risks; Heart Disease Risk Factors; Heart diseases; Humanities and Social Sciences; Humans; Hypoglycemia; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-like growth factors; Ischemia; Mortality; multidisciplinary; Myocardial infarction; Observational studies; Overweight; Peptidase; Percutaneous Coronary Intervention - adverse effects; Risk Factors; Science; Science (multidisciplinary); Serum levels; Treatment Outcome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-09059-2

Dipeptidyl-peptidase-4 inhibitors (DPP4i) have been the most used antidiabetic medications worldwide due to their good safety profiles and tolerability with a low risk of hypoglycemia, however, large cardiovascular outcome trials (CVOTs) have not shown any significant the prognostic superiority. On the contrary, since observational studies have suggested the effects of DPP4i are enhanced some populations, such as Asians and those who without overweight, their prognostic benefit is still under debate. The aim of this study was thus to assess the prognostic impact of DPP4i in patients with both diabetes and coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) through the insulin-like growth factor-1 (IGF-1) axis, a substrate of DPP4. This single-center analysis involved consecutive Japanese diabetic patients who underwent PCI for the first time between 2008 and 2018 (n = 885). Primary and secondary endpoints were set as cardiovascular (CV) death and the composite of CV death, non-fatal myocardial infarction and ischemic stroke (3P-MACE). Serum levels of IGF-1 and its main binding protein (insulin-like growth factor binding protein-3: IGFBP-3) were measured. In consequences, unadjusted Kaplan–Meier analyses revealed reduced incidences of CV-death and 3P-MACE by DPP4i, which was particularly enhanced in patients who were not overweight (BMI ≤ 25). Multivariate Cox hazard analyses consistently indicated reduced risks of CV death by DPP4i at PCI (hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.16–0.82, p = 0.01) and 3P-MACE (HR 0.47, 95% CI 0.25–0.84, p = 0.01), respectively. Moreover, elevated IGF-1 activity indicated by the IGF-1/IGFBP-3 ratio was associated with decreased risks of both endpoints and it was significantly higher in patients with DPP4i (p