Table 1.
Pre-clinical and clinical studies investigating the effects of novel anti-diabetic agents on stent-related complications.
| GLP-1 RAs | Type Of-Study | Molecule | Setting | Main Results |
|---|---|---|---|---|
| Infarct size/periprocedural ischemia | ||||
| Timmers et al., 2009 | Preclinical study | Exenatide | Porcine model of ischemia/reperfusion | ↓ infarct size ↑ systolic and diastolic cardiac function |
| Ashraf et al., 2009 | Preclinical study | Liraglutide | Induced myocardial infarction in diabetic and non-diabetic mice | ↓ infarct size ↓ cardiac rupture ↑ survival ↑ expression and activity of cardioprotective genes (Akt, GSK3 beta, PPAR beta-delta, Nrf-2, and HO-1) |
| Lønborg et al., 2012 | Clinical study | Exenatide | Patients with STEMI and TIMI flow 0/1 undergoing primary PCI | ↓ infarct size (particularly, in those patients with a short duration of ischemia - ≤132 min) |
| Woo et al., 2013 | Clinical study | Exenatide | Patients with STEMI and TIMI flow 0 undergoing primary PCI | ↓ infarct size ↑ left ventricular function (lower E/E' and improved strain parameters) |
| Chen et al., 2016 | Clinical study | Liraglutide | Patients with STEMI undergoing primary PCI | ↑ myocardial salvage index ↓ infarct size ↓ serum CRP |
| No reflow | ||||
| Chen et al., 2015 | Clinical study | Liraglutide | Patients with STEMI undergoing primary PCI | ↑ left ventricular function at 3 months post PCI ↓ no reflow ↓ stress hyperglycaemia |
| Chen et al., 2016 | Clinical study | Liraglutide | Patients with STEMI undergoing PCI | ↓ no reflow ↓ serum CRP at 6 h post PCI |
| ISR | ||||
| Shi et al., 2015 | Preclinical study | Liraglutide | VSMCs from rat thoracic aorta | ↓ migration and proliferation of VSMCs Inhibition of PI3K/Akt and ERK1/2 signaling pathways |
| Hirata et al., 2013 | Preclinical study | Exendin-4 | Vascular injury in C57BL/6 mice | ↓ neointima hyperplasia |
| Xia et al., 2020 | Preclinical study | Liraglutide | Diabetic pigs undergoing DES implantation | ↓ neointima hyperplasia via regulation of glycaemic variability, NLRP3 inflammasome and IL-10 |
| DPP-4i | Type of study | Molecule | Setting | Main results |
| ISR | ||||
| Terawaki et al., 2014 | Preclinical study | Linagliptin | Vascular injury in C57BL/6 mice | ↓ neointima hyperplasia ↓ VSMCs proliferation |
| Lee et al., 2019 | Preclinical study | Vildagliptin | Nanofibrous vildagliptin-eluting stents in diabetic rats | ↓ neointima formation ↓ VSMCs proliferation |
| Stent thrombosis/Reinfarction | ||||
| Leibovitz et al., 2013 | Clinical study | Sitagliptin | Diabetic patients presenting with ACS | ↓in-hospital complications ↓ 30-day MACEs (stent thrombosis, urgent revascularization, post event ischemia, 30-day mortality, re-infarction or re-ischemia, re-admission, stroke/TIA) |
| SGLT-2i | Type of study | Molecule | Setting | Main results |
| Infarct size/periprocedural ischemia | ||||
| Andreadou et al., 2017 | Preclinical study | Empaglifozin | Murine model of ischemia/reperfusion | In vivo: ↓ infarct size ↑ myocardial function In vitro: ↑ STAT3 expression and activation with antioxidant and anti-inflammatory action ↓ myocardial IL-6 and iNOS |
| Lahnwong et al., 2020 | Preclinical study | Dapaglifozin | Murine model of ischemia/reperfusion | ↓ infarct size ↓ cardiac apoptosis and ↑ cardiac mitochondrial function ↑ left ventricular function ↓ arrhythmias |
| ISR | ||||
| Mori et al., 2019 | Preclinical study | Luseoglifozin | Femoral artery wire injury in mice | ↓ neointima hyperplasia |
| Hashikata et al., 2020 | Clinical study | Empaglifozin | Diabetic patients undergoing PCI | ↓ neointima hyperplasia |
| Contrast-induced acute kidney injury | ||||
| Huang et al., 2022 | Preclinical study | Dapaglifozin | In vitro hypoxia model; diabetic rats receiving contrast media and exhibiting induced CI-AKI | In vitro: ↓ oxygen consumption, HIF-1α, HE4, NF-κB expression and apoptotic cells In vivo: ↓ serum creatinine, urea nitrogen, TUNEL-positive tubular cells, HIF-1α, HE4, NF-κB expression, and histopathological scores related to CI-AKI |
GLP-1 RAs, glucagon-like peptide-1 receptor agonists; STEMI, ST elevation myocardial infarction; TIMI, thrombolysis in myocardial infarction; PPAR, peroxisome proliferator-activated receptor; PCI, percutaneous coronary intervention; HO-1, heme oxygenase-1; CRP, C-reactive protein; PI3K, phosphatidylinositol 3-kinases; DES, drug eluting stents; NLRP3, NLR family pyrin domain containing 3; IL, interleukin; DPP-4i, dipeptidyl peptidase-4 inhibitors; VSMCs, vascular smooth muscle cells; ACS, acute coronary syndromes; MACEs, major adverse cardiac events; TIA, transient ischaemic attack; SGLT-2i, sodium-glucose co-transporter-2 inhibitors; STAT-3, signal transducer and activator of transcription 3; iNOS, inducible nitric oxide synthase; CI-AKI, contrast-induced acute kidney injury; HIF-1, hypoxia-inducible factor 1-alpha; HE4, human epididymis protein-4; NF-kB, nuclear factor kappa-light-chain-enhancer of activated B cells; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling.