Gemiglo (gemigliptin) / Sanofi, LG Chem - LARVOL DELTA

Effectiveness of gemigliptin on risk of major adverse kidney events in people with type 2 diabetes: A Korean cohort study. (PubMed, Diabetes Obes Metab) - No abstract available

Adverse events • Journal • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

The anti-senescence effect of DPP-IV inhibitor gemigliptin on vascular tissue (EASD 2024) - "Gemigliptin exerts notable efficacy in mitigating stress-induced apoptosis and accelerated senescence in both endothelial cells and the aortas of diabetic mice, with its anti-senescence effects appearing independent of its glucose-lowering properties. These findings underscore the potential clinical significance of Gemigliptin beyond its conventional use, warranting further exploration to delineate its therapeutic implications in the context of aging-related vascular pathologies."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CDKN1A • NOS3 • SIRT1

Gemigliptin mitigates TGF-β-induced renal fibrosis through FGF21-mediated inhibition of the TGF-β/Smad3 signaling pathway. (PubMed, Biochem Biophys Res Commun) - "However, the protective effects of gemigliptin were blocked when FGF21 expression was knocked down in TGF-β-treated HK-2 cells. These results indicate that gemegliptin has the potential to exhibit protective effects against TGF-β-induced renal fibrosis by elevating FGF21 expression levels in cultured human proximal tubular epithelial cells."

Journal • Diabetes • Fibrosis • Immunology • Metabolic Disorders • Type 2 Diabetes Mellitus • FGF21 • SMAD3 • TGFB1

Gemigliptin Attenuates TGF-ß-Induced Renal Fibrosis by Inhibiting the TGF-ß/Smad3 Signaling Pathway through the Upregulation of FGF21 Expression (ADA 2024) - "These results indicate that gemigliptin has the potential to confer protective effects against TGF-β-induced renal fibrosis by elavating FGF21 expression levels in the cultured human proximal tubular epithelial cells."

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • FGF21 • SMAD3 • TGFB1

Improvement effect of gemigliptin on salivary gland dysfunction in exogenous methylglyoxal-injected rats. (PubMed, Heliyon) - "Overall, gemigliptin protected the salivary gland cells from ROS-mediated cell death, reduced the accumulation of amylase and mucins in the salivary glands, and enhanced the salivary function by upregulating aquaporin 5 expression, and it exerted protective effects against MGO-induced salivary gland dysfunction by enhancing the anti-glycation, antioxidant, and salivary secretion activities. Our findings suggest gemigliptin as a potential therapeutic for patients with salivary gland dysfunction caused by the complications of diabetes."

Journal • Preclinical • Diabetes • Infectious Disease • Metabolic Disorders • Xerostomia

Gemigliptin alleviates succinate induced ER stress and activation of hepatic stellate cells (APASL 2024) - "This study showed the involvement of ER stress in the activation of succinate-induced LX-2 HSCs and gemigliptin significantly reduced ER stress in HSC activation. Therefore, gemigliptin may become an anti-fibrotic agent and targeting to succinate and ER stress may be a promising therapeutic in the management of liver fibrosis."

Fibrosis • Hepatology • Immunology • Liver Cirrhosis • CXCR3 • SUCNR1

Gemigliptin, a potent selective dipeptidyl peptidase 4 inhibitor, protects endothelial progenitor cells by oxidative stress via caspase-3 dependent pathway. (PubMed, Biochem Biophys Rep) - "In conclusion, gemigliptin dose dependently effects the EPCs viability and morphology through Caspase-3 signaling. Our results are the first report of gemigliptin effect on EPC viability and morphology."

Journal • Cardiovascular • Diabetes • Metabolic Disorders • ANXA5 • BCL2 • CASP3

Gemigliptin Improves Salivary Gland Dysfunction in D-Galactose-Injected Aging Rats. (PubMed, Pharmaceutics) - "In sum, gemigliptin was shown to improve D-gal-induced decline in the salivary gland function of aged rats through its anti-glycation and antioxidant activities. Gemigliptin shows promise as a treatment strategy for patients experiencing decreased salivary function associated with their advancing age."

Journal • Preclinical • Xerostomia

A Multicenter, Randomized, Open-Label Study to Compare the Effects of Gemigliptin Add-on or Escalation of Metformin Dose on Glycemic Control and Safety in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Treated with Metformin and SGLT-2 Inhibitors (SO GOOD Study). (PubMed, J Diabetes Res) - "Gemigliptin add-on therapy may be more effective than metformin dose escalation in patients with T2DM insufficiently controlled using metformin and SGLT2 inhibitors, without safety concerns. This trial is registered with CRIS_number: KCT0003520."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The effect of gemigliptin treatment on immune parameters including regulatory T cells in patients with type 2 diabetes and moderate to very severe chronic renal impairment. (PubMed, Medicine (Baltimore)) - "Treatment with gemigliptin for 3 and 6 months did not significantly alter the number, percentage, or ratio of circulating Treg cells in patients with type 2 diabetes and CKD. Therefore, the administration of gemigliptin may help maintain regulatory T cells or have no significant impact."

Journal • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • CD4 • FOXP3 • IL2RA • IL7R

Gemigliptin, a DPP4 inhibitor, ameliorates nonalcoholic steatohepatitis through AMP-activated protein kinase-independent and ULK1-mediated autophagy. (PubMed, Mol Metab) - "Collectively, these results suggest that gemigliptin ameliorated NASH via AMPK-independent, ULK1-mediated effects on autophagy."

Journal • Addiction (Opioid and Alcohol) • Diabetes • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Type 2 Diabetes Mellitus

Comparison of the Effects of Dapagliflozin and Gemigliptin on Ketone Metabolism and Cardiac Remodeling in Type 2 Diabetes (clinicaltrials.gov) - P4 | N=122 | Recruiting | Sponsor: Wonju Severance Christian Hospital | Trial completion date: Jun 2023 ➔ Jun 2025 | Trial primary completion date: Dec 2022 ➔ Dec 2024

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy of Gemigliptin Add-on to Dapagliflozin and Metformin in Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Study (SOLUTION). (PubMed, Endocrinol Metab (Seoul)) - "Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin."

Clinical • Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

A Study to Evaluate the Efficacy and Safety of Gemigliptin in Type 2 Diabetes Who Have Inadequate GlycemIc Control With Dapagliflozin and Metformin (SOLUTION Study) (clinicaltrials.gov) - P3 | N=315 | Completed | Sponsor: LG Chem | Active, not recruiting ➔ Completed | Trial completion date: May 2022 ➔ Nov 2022

Trial completion • Trial completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Gemigliptin Alleviates Succinate-Induced Hepatic Stellate Cell Activation by Ameliorating Mitochondrial Dysfunction. (PubMed, Endocrinol Metab (Seoul)) - "Furthermore, in the mouse model of NASH-induced liver fibrosis, gemigliptin alleviated both liver fibrosis and mitochondrial dysfunction. Gemigliptin protected against HSC activation and liver fibrosis by alleviating mitochondrial dysfunction and ROS production, indicating its potential as a strategy for preventing the development of liver disease."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Non-alcoholic Steatohepatitis

Gemigliptin exerts protective effects against doxorubicin-induced hepatotoxicity by inhibiting apoptosis via the regulation of fibroblast growth factor 21 expression. (PubMed, Biochem Biophys Res Commun) - "These results indicate that gemigliptin exhibits protective effects against doxorubicin-induced hepatotoxicity by upregulating the fibroblast growth factor 21 expression levels in the cultured murine hepatocyte AML12 cells."

Journal • Cardiovascular • Diabetes • Hepatology • Metabolic Disorders • Oncology • Type 2 Diabetes Mellitus • FGF21

Comparison of the Effects of Dapagliflozin and Gemigliptin on Ketone Metabolism and Cardiac Remodeling in Type 2 Diabetes (clinicaltrials.gov) - P4 | N=122 | Recruiting | Sponsor: Wonju Severance Christian Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparison of the Effects of Dapagliflozin and Gemigliptin on Ketone Metabolism and Cardiac Remodeling in Type 2 Diabetes (clinicaltrials.gov) - P4; N=122; Not yet recruiting; Sponsor: Wonju Severance Christian Hospital

New P4 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Hepatoprotective effects of gemigliptin and empagliflozin in a murine model of diet-induced non-alcoholic fatty liver disease. (PubMed, Biochem Biophys Res Commun) - "Furthermore, in these three groups, the galectin-3 and interleukin 33-induced activity of tumor necrosis factor-α was inhibited, thereby preventing the progression of liver fibrosis. These findings suggest that the GEMI, EMPA, and GEMI + EMPA treatments ameliorate hepatic steatosis, inflammation, oxidative stress, and fibrosis in CDAHFD-induced NAFLD mouse models."

Journal • Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Non-alcoholic Fatty Liver Disease • Oncology • IL33 • MAPK8

Effect of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Biomarkers of Kidney Injury and Vascular Calcification in Diabetic Kidney Disease: A Randomized Controlled Trial. (PubMed, J Diabetes Res) - P=N/A | "We evaluated the effects of a potent DPP4 inhibitor (gemigliptin) on these processes among patients with diabetic kidney disease (DKD)...Clinical Trials. This trial is registered with ClinicalTrials.Gov Identifier NCT04705506."

Biomarker • Clinical • Journal • Diabetes • Diabetic Nephropathy • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • FABP1 • LCN2

Antidiabetic effect of gemigliptin: a systematic review and meta-analysis of randomized controlled trials with Bayesian inference through a quality management system. (PubMed, Sci Rep) - "Further, gemigliptin was more effective than other OADs in HbA1c and HOMA-β in Bayesian inference analysis and statistically significant to other OADs in HbA1c and HOMA-β in sensitivity analysis excluding metformin. However, to confirm the results, more studies need to be analysed and the minimum clinically important difference must be applied."

Journal • Retrospective data • Review • Dyslipidemia

A Study to Evaluate the Efficacy and Safety of Gemigliptin in Type 2 Diabetes Who Have Inadequate GlycemIc Control With Dapagliflozin and Metformin (SOLUTION Study) (clinicaltrials.gov) - P3; N=315; Active, not recruiting; Sponsor: LG Chem; Not yet recruiting ➔ Active, not recruiting; Trial primary completion date: Jan 2022 ➔ May 2021

Clinical • Enrollment closed • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Cardiovascular events and all-cause mortality in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors: An extensive meta-analysis of randomized controlled trials. (PubMed, Nutr Metab Cardiovasc Dis) - "As a class, DPP4i are not associated with any increase or reduction of MACE, all-cause mortality, and heart failure. Saxagliptin seems to be associated with an increased risk of hospitalization for heart failure."

Journal • Retrospective data • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

Anti-inflammatory Effects of Empagliflozin and Gemigliptin on LPS-Stimulated Macrophage via the IKK/NF-κB, MKK7/JNK, and JAK2/STAT1 Signalling Pathways. (PubMed, J Immunol Res) - "Our study demonstrated the anti-inflammatory effects of empagliflozin and gemigliptin via IKK/NF-κB, MKK7/JNK, and JAK2/STAT1 pathway downregulation in macrophages. In all cases, combined empagliflozin and gemigliptin treatment showed greater anti-inflammatory properties."

Journal • Diabetes • Genetic Disorders • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • Obesity • CCL3 • CXCL10 • IFNG • IL1B • IL6 • MAP2K4 • PTGS2 • TNFA

[VIRTUAL] EFFECT OF GEMIGLIPTIN ON BIOMARKERS OF KIDNEY INJURY AND VASCULAR CALCIFICATION IN DIABETIC NEPHROPATHY: A RANDOMIZED CONTROLLED TRIAL (ERA-EDTA 2021) - "Our study shows that gemigliptin has significant benefits on biomarkers of renal tubular injury and vascular calcification in patients with diabetic nephropathy, but gemigliptin does not affect on renal function and coronary calcification compared with control. The larger and longer follow-up will be essential to determine these beneficial effects."

Biomarker • Clinical • Diabetes • Diabetic Nephropathy • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • FABP1 • LCN2