Suiny (anagliptin) / Kowa, Suzuken - LARVOL DELTA

Gastric Emptying Delay with Pre-Meal Administration of Metformin and Anagliptin in Type 2 Diabetes: Effects on Postprandial Glucose and Triglyceride Levels in a Two-Case Report. (PubMed, Am J Case Rep) - "CONCLUSIONS Pre-meal administration of metformin and anagliptin reduced postprandial glucose and triglyceride concentrations, potentially through a delay in gastric emptying. Thus, changing the timing of medication may improve their therapeutic effects."

Journal • Diabetes • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Type 2 Diabetes Mellitus

EffiCacy and safety of ANagliptin when added to iNsulin and metformin therapy in patients with uncontrolled type 2 diAbetes; randomized, placebo-controlled, double-blind, multicentre trial (CANNA study). (PubMed, Diabetes Obes Metab) - No abstract available

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Pyrimidine derivatives as multifaceted antidiabetic agents: A comprehensive review of structure-activity relationships, mechanisms, and clinical potential. (PubMed, Eur J Med Chem) - "The mechanistic insights from molecular docking and QSAR studies explain their interaction with different antidiabetic targets and clinical relevance is attributed to anagliptin and tolimidone. New vogue patterns, such as AI-drug designing and conjugate development, are discussed for next-generation therapies. The review covers also the perspectives on challenges, opportunities, and comparative merits over other heterocyclic scaffolds, making these pyrimidine derivatives versatile leads in exploring antidiabetic aspects."

Journal • Review • Developmental Disorders • Diabetes • Metabolic Disorders

The Mechanism of Leptin Resistance in Obesity and Therapeutic Perspective. (PubMed, Adv Exp Med Biol) - "While add-on therapy with anagliptin, metformin and miglitol reduce leptin concentrations, the use of long-acting leptin analogs, and exendin-4 lead to the recovery of leptin sensitivity. Although approaches to correcting leptin resistance have shown some success, no clinically effective application has been developed to date. Due to the impairment of central and peripheral leptin signaling, as well as the extensive integration of leptin-sensitive metabolic pathways with other neurons, the effectiveness of methods used to eliminate leptin resistance is extremely limited."

Journal • Review • Dyslipidemia • Genetic Disorders • Hypertriglyceridemia • Inflammation • Obesity • POMC-null Obesity • LEP • LEPR • SOCS3

Vasorelaxant mechanisms of the antidiabetic anagliptin in rabbit aorta: roles of Kv channels and SERCA pump. (PubMed, Acta Diabetol) - "Based on these results, we suggest that anagliptin-induced vasorelaxation in rabbit aortic smooth muscle occurs by activating Kv channels and the SERCA pump, independent of other vascular K+ channels, cAMP/PKA- or cGMP/PKG-related signaling pathways, and the endothelium."

Journal • Preclinical

Role of anagliptin, a dipeptidyl peptidase-4 inhibitor, in managing type 2 diabetes: A systematic review and meta-analysis. (PubMed, Medicine (Baltimore)) - "Anagliptin positively affects glucose control and is safe for managing T2D. Its low-density lipoprotein cholesterol-lowering effect warrants further investigation."

Clinical • Journal • Retrospective data • Review • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus • APOB

SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS SUPPRESS RECURRENCE AFTER ATRIAL FIBRILLATION ABLATION IN PATIENTS WITH HIGH BODY MASS INDEX (ACC 2024) - "Tofogliflozin can suppress AF recurrence after CA, especially in patients with type-2 DM and high body mass index."

Clinical • Atrial Fibrillation • Cardiovascular

Dipeptidyl peptidase-4 inhibitor and sodium-glucose cotransporter 2 inhibitor additively ameliorate hepatic steatosis through different mechanisms of action in high-fat diet-fed mice. (PubMed, Diabetes Obes Metab) - "The combination therapy with the DPP-4 inhibitor anagliptin and the SGLT2 inhibitor luseogliflozin inhibits fat deposition in the liver via anti-inflammatory effects during the early phase of diet-induced liver steatosis."

Journal • Preclinical • Diabetes • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Effect of Anagliptin on Vascular Injury in the Femoral Artery of Type 2 Diabetic Rats. (PubMed, Biol Pharm Bull) - "Furthermore, the femoral artery showed increased wall thickness in OLETF rats compared to LETO rats, but anagliptin administration reduced the thickening. This study suggests that long-term anagliptin administration can reduce oxidative stress in femoral arteries and improve vascular injury."

Journal • Preclinical • Cardiovascular • Diabetes • Metabolic Disorders • Peripheral Arterial Disease • Type 2 Diabetes Mellitus

DPP-4 Inhibitor and SGLT2 Inhibitor Additively Ameliorate Hepatic Steatosis in NAFLD Model Mice through Different Action Mechanisms (ADA 2023) - "Luseogliflozin (Luseo) has been reported to improve NAFLD in T2DM model mice by affecting factors related to fatty acid synthesis and beta oxidation. Anagliptin (Ana) improves NAFLD in mice by altering the M1/M2 macrophage ratio...Combination of two drugs markedly ameliorated hepatocyte fat deposition. Thus, it is likely that both DPP-4 inhibitor and SGLT2 inhibitor contributed to the improvement of NAFLD through different action mechanisms."

Preclinical • Diabetes • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Type 2 Diabetes Mellitus • CCL3 • IL6

Effects of Tofogliflozin and Anagliptin Alone or in Combination on Glucose Metabolism and Atherosclerosis-Related Markers in Patients with Type 2 Diabetes Mellitus. (PubMed, Clin Pharmacol) - "The increase in sLOX-1 and IL-6 levels, which indicates the response of scavenger receptors to oxidized low-density lipoproteins in people with T2DM, is mitigated following TOFO and ANA combination therapy. TOFO alone or in combination with ANA may be beneficial for preventing atherosclerosis development in people with T2DM, in addition to its effect on improving HbA1c levels."

Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus • IL6

Dipeptidyl peptidase 4 inhibitor reduces tumor-associated macrophages and enhances anti-PD-L1-mediated tumor suppression in non-small cell lung cancer. (PubMed, Clin Transl Oncol) - "Anagliptin can enhance PD-L1 blockade efficacy in NSCLC by inhibiting macrophage differentiation and M2 macrophage polarization, and combination therapy may be a promising strategy for treating PD-L1 blockade therapy-resistant patients with NSCLC."

IO biomarker • Journal • Diabetes • Immune Modulation • Lung Cancer • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • IFNG

PLEIOTROPIC EFFECTS OF SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS SUPPRESS RECURRENCE OF ATRIAL FIBRILLATION AFTER CATHETER ABLATION (ACC-WCC 2023) - "Eighty AF patients with type-2 DM were randomized to Tofogliflozin (SGLT2i) group or Anagliptin (DPP4i) group with a computer-generated random sequence, which was stratified by left atrial diameter and AF type (paroxysmal or non-paroxysmal) at screening. Pleiotropic effects of SGLT2i may suppress AF recurrence after CA in patients with type-2 DM."

Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparison of Adverse Events Occurred During Administration of Dipeptidyl Peptidase-4 Inhibitor in Patients with Diabetes Using FDA Adverse Event Reporting System. (PubMed, Clin Drug Investig) - "Although it is impossible to select a DPP-4 inhibitor with aROR of < 1.000 of all occurrences of adverse events, these results may be used for drug selection when the patient has adverse events that need to be avoided. We provided the sample code of software R that can reproduce the results."

Adverse events • Journal • Acute Kidney Injury • Diabetes • Immunology • Metabolic Disorders • Nephrology • Renal Disease

Anagliptin twice-daily regimen improves glycemic variability in subjects with type 2 diabetes: Double-Blind, Randomized Controlled Trial. (PubMed, Diabetes Obes Metab) - "The anagliptin BID regimen for the treatment of type 2 diabetes was superior in blood glucose control after dinner to improve glycemic variability, as indicated by MAGE and TIR but equivalent to the QD regimen in terms of HbA1c and FPG."

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

Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors on Outcomes After Catheter Ablation for Atrial Fibrillation. (PubMed, JACC Clin Electrophysiol) - "Compared with anagliptin, tofogliflozin achieved greater suppression of AF recurrence after CA in patients with type 2 diabetes mellitus."

Journal • Atrial Fibrillation • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • NPPB

Therapeutic Effects of Switching to Anagliptin from Other DPP-4 Inhibitors in T2DM Patients with Inadequate Glycemic Control: A Non-interventional, Single-Arm, Open-Label, Multicenter Observational Study. (PubMed, Diabetes Ther) - "In patients with T2DM poorly controlled by other DPP-4 inhibitors, HbA1c levels were significantly decreased after switching to anagliptin. Given that the change in HbA1c was greater in patients without comorbidities than in patients with comorbidities, switching to anagliptin before adding other oral hypoglycemic agents (OHAs) may be an option in patients without comorbidities."

Journal • Observational data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparison of the Effectiveness of Once-Daily Alogliptin/Metformin and Twice-Daily Anagliptin/Metformin Combination Tablet in a Randomized, Parallel-Group, Open-Label Trial in Japanese Patients with Type 2 Diabetes. (PubMed, Diabetes Ther) - "The once-daily alogliptin/metformin combination tablet was non-inferior to the twice-daily anagliptin/metformin combination tablet LD in Japanese patients with type 2 diabetes."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

FABP4 secreted by M1-polarized macrophages promotes synovitis and angiogenesis to exacerbate rheumatoid arthritis. (PubMed, Bone Res) - "BMS309403 and anagliptin inhibited FABP4 expression in synovial M1-polarized macrophages to alleviate RA development. Hence, FABP4 may represent a potential target for RA therapy."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • FABP4 • TSC1

Safety and efficacy of once weekly dipeptidyl-peptidase-4 inhibitor trelagliptin in type-2 diabetes: A meta-analysis. (PubMed, Diabetes Metab Syndr) - "Once weekly trelagliptin has good glycaemic efficacy and well tolerated in people with T2DM."

Journal • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT-4/lactate-mediated intracellular acidosis. (PubMed, Exp Ther Med) - "Additionally, anagliptin reversed the aberrant transmembrane extracellular/intracellular pH gradient by suppressing MCT-4-mediated lactate excretion, while also reducing mitochondrial membrane potential and inducing apoptosis. These data revealed a novel function of anagliptin in regulating lactate excretion from cancer cells, suggesting that anagliptin may be used as a potential treatment for cancer."

Journal • Preclinical • Colon Cancer • Colorectal Cancer • Metabolic Disorders • Oncology • Solid Tumor • PCNA

Effect of Anagliptin versus Sitagliptin on Renal Function: Subanalyzes from the REASON Trial. (PubMed, Diabetes Metab Syndr Obes) - "The difference in eGFR was affected by the differences in HbA1c level and BP, and the difference in the UACR was affected by the differences in LDL-C level and BP, which were reduced only in the ANA group. These findings imply that the effects of DPP-4 inhibitors on renal function, especially on UACR, may be different between the types of DPP-4 inhibitors."

Journal • Diabetes • Dyslipidemia • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

Anagliptin prevents lipopolysaccharide (LPS)- induced inflammation and activation of macrophages. (PubMed, Int Immunopharmacol) - "Lastly, the protective properties of anagliptin on LPS- treated macrophages, including the inhibitory effects on inflammation and the NF-κB pathway, were dramatically abolished by the overexpression of RIP1 in macrophages. Collectively, anagliptin prevented LPS-induced inflammation and activation of P338D1 macrophages by repressing the expression level of RIP1."

IO biomarker • Journal • Diabetes • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • Septic Shock • Type 2 Diabetes Mellitus • HMGB1 • RIPK1 • TLR4

Anagliptin Monotherapy for Six Months in Patients With Type 2 Diabetes Mellitus and Hyper-Low-Density Lipoprotein Cholesterolemia Reduces Plasma Levels of Fasting Low-Density Lipoprotein Cholesterol and Lathosterol: A Single-Arm Intervention Trial. (PubMed, J Clin Med Res) - "Furthermore, fasting plasma lathosterol levels were negatively correlated with preprandial glucagon-like peptide-1 (GLP-1) levels after anagliptin treatment. Anagliptin monotherapy may have a beneficial effect on lipid metabolism, which could be mediated by the inhibition of hepatic cholesterol synthesis rather than the inhibition of intestinal lipid transport."

Clinical • Journal • Monotherapy • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Anagliptin alleviates lipopolysaccharide-induced inflammation, apoptosis and endothelial dysfunction of lung microvascular endothelial cells. (PubMed, Exp Ther Med) - "In conclusion, anagliptin alleviated inflammation, apoptosis and endothelial dysfunction in LPS-induced HPMVECs via modulating HMGB1/RAGE expression. These data provide a basis for use of anagliptin in ALI treatment."

Journal • Acute Lung Injury • Immunology • Inflammation • Pneumonia • Respiratory Diseases • DPP4 • HMGB1