Gemigliptin: Newer promising gliptin for type 2 diabetes mellitus

Baek

Korean J Physiol Pharmacol

2018

Dipeptidyl peptidase4 (DPP4) inhibitors such as gemigliptin are anti-diabetic drugs elevating plasma concentration of incretins such as GLP-1. In addition to the DPP4 inhibition, gemigliptin might directly improve the functions of vessels under pathological conditions. To test this hypothesis, we investigated whether the acetylcholine-induced endothelium dependent relaxation (ACh-EDR) of mesenteric arteries (MA) are altered by gemigliptin pretreatment in Spontaneous Hypertensive Rats (SHR) and in Wistar-Kyoto rats (WKY) under hyperglycemia-like conditions (HG; 2 hr incubation with 50 mM glucose). ACh-EDR of WKY was reduced by the HG condition, which was significantly recovered by 1 µM gemigliptin while not by saxagliptin and sitagliptin up to 10 µM. The ACh-EDR of SHR MA was also improved by 1 µM gemigliptin while similar recovery was observed with higher concentration (10 µM) of saxagliptin and sitagliptin. The facilitation of ACh-EDR by gemigliptin in SHR was not observed under pretreatment with NOS inhibitor, L-NAME. In the endotheliumdenuded MA of SHR, sodium nitroprusside induced dose-dependent relaxation was not affected by gemigliptin. The ACh-EDR in WKY was decreased by treatment with 30 µM pyrogallol, a superoxide generator, which was not prevented by gemigliptin. Exendin-4, a GLP-1 analogue, could not enhance the ACh-EDR in SHR MA. The present results of ex vivo study suggest that gemigliptin enhances the NOS-mediated EDR of the HG-treated MA as well as the MA from SHR via GLP-1 receptor independent mechanism.

Section: Introductionmentioning

confidence: 99%

Potentiation of endothelium-dependent vasorelaxation of mesenteric arteries from spontaneously hypertensive rats by gemigliptin, a dipeptidyl peptidase-4 inhibitor class of anti-diabetic drug

Baek

Korean J Physiol Pharmacol

2018

“…Lastly, in terms of metabolism of DDP-4 inhibitors, saxagliptin and gemigliptin are metabolized by CYP3A4 and therefore can be used with immunosuppressive agents. All gliptins are excreted predominantly by the kidney as an unchanged parent compound, excluding linagliptin and gemigliptin, which are excreted mainly by biliary excretion and therefore, do not need renal dose adjustment [ 60 , 61 ].…”

Section: Antidiabetic Agentsmentioning

confidence: 99%

Current Pharmacological Intervention and Medical Management for Diabetic Kidney Transplant Recipients

et al. 2021

Hyperglycemia after kidney transplantation is common in both diabetic and non-diabetic patients. Both pretransplant and post-transplant diabetes mellitus are associated with increased kidney allograft failure and mortality. Glucose management may be challenging for kidney transplant recipients. The pathophysiology and pattern of hyperglycemia in patients following kidney transplantation is different from those with type 2 diabetes mellitus. In patients with pre-existing and post-transplant diabetes mellitus, there is limited data on the management of hyperglycemia after kidney transplantation. The following article discusses the nomenclature and diagnosis of pre- and post-transplant diabetes mellitus, the impact of transplant-related hyperglycemia on patient and kidney allograft outcomes, risk factors and potential pathogenic mechanisms of hyperglycemia after kidney transplantation, glucose management before and after transplantation, and modalities for prevention of post-transplant diabetes mellitus.

“…2 Gemigliptin is a potent DPP-4 inhibitor that has been approved for use in patients with type 2 diabetes, and it has pleiotropic effects in addition to its glucose-lowering effect, including inhibition of lipopolysaccharide (LPS)-induced proin ammatory effects in vascular endothelial cells by attenuating NF-kappa B and c-Jun NH (2)-terminal kinase (JNK) signaling via an AMP-activated protein kinase (AMPK)-dependent mechanism. 3 A recent study found that gemigliptin attenuated the calci cation of the abdominal aorta as well as RUNX2 and phosphate-induced Pit-1 mRNA expression, and reactive oxygen species formation. Therefore, gemigliptin could bene t vascular calci cation in patients with a high risk of disease, especially diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 99%

Effect of Dipeptidyl Peptidase- 4 (DPP-4) Inhibitor on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Nephropathy: A Randomized Controlled Trial

Trakarnvanich

Satirapoj

Suraamornkul

et al. 2021

Preprint

Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control and have pleiotropic effects on kidney injury, albuminuria and vascular inflammation, especially in animal models. We plan to evaluate the effects of a potent DPP4 inhibitor (gemigliptin) on these processes in diabetic nephropathy patients.Methods: This was a multicenter, prospective, randomized, placebo-controlled trial. A total of 201 participants were enrolled and randomly assigned to a group treated with 50 mg gemigliptin daily with standard care of diabetes mellitus for 6 months. The changes in coronary calcium score (CAC score), cardio-ankle vascular index (CAVI), estimated glomerular filtration rate (GFR), vascular calcification and tubular renal injury markers were evaluated at baseline and 6 months.Results: In total, 182 patients completed the study. Significant reductions in hemoglobin A1C levels were observed in both groups. The changes in CAC score, CAVI, estimated GFR and proteinuria over the 6 months of the study did not significantly differ between the groups. However, biomarkers of vascular calcification, including serum bone alkaline phosphatase, and kidney injury, including urine neutrophil gelatinase-associated lipocalin (NGAL)/Cr and urine liver fatty acid-binding protein (L-FABP)/Cr, were improved significantly in the gemigliptin treatment group compared to the control group. No serious adverse event was observed during the study.Conclusion: Our study shows that gemigliptin significantly improves renal tubular injury biomarkers and vascular calcification in patients with diabetic nephropathy; however, gemigliptin does not affect renal function or coronary calcification compared with the control. A larger and longer follow-up will be essential to determine these beneficial effects.Clinical trialsClinicalTrials.Gov Identifier: NCT04705506