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

Repositioning Gemigliptin for the Alleviation of Thioacetamide-Induced Liver Fibrosis in Rats: Targeting TLR4/MAPK, SIRT1/AMPK/Nrf2, PI3K/AKT/mTOR Axis and Apoptosis. (PubMed, Eur J Pharm Sci) - "By controlling the "Bcl-2/Bax/Caspase-3" pathway, we also showed that gemigliptin prevented hepatocyte apoptosis. In summary, these results imply that gemigliptin inhibits the advancement of liver fibrosis via a variety of pathways and point to the possibility of its future application in liver fibrosis treatment."

IO biomarker • Journal • Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • AMPK • BCL2 • CASP3 • SIRT1 • TLR4

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