Suiny (anagliptin) / Kowa, Suzuken - LARVOL DELTA

Efficacy and safety of anagliptin add-on therapy in patients with type 2 diabetes inadequately controlled by metformin and empagliflozin (EASD 2026) - P3 | "The addition of anagliptin to a metformin and empagliflozin regimen significantly improved glycemic control without increasing safety concerns or negatively impacting blood pressure and renal function. Triple therapy with anagliptin, metformin, and empagliflozin represents a potent and safe therapeutic option for patients with T2DM requiring further glucose lowering."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Anagliptin Added to Metformin and Empagliflozin 25 mg in Patients with Type 2 Diabetes: A 24-Week Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with 28-Week Open-Label Extension (ADA 2026) - "Anagliptin as add-on therapy to metformin and empagliflozin 25 mg significantly improves glycemic control and β-cell function with a favorable safety profile in T2DM patients inadequately controlled on dual therapy."

Clinical • P3 data • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Association Between Dipeptidyl Peptidase-4 Inhibitor Use and Acute Kidney Injury in Patients With Diabetes Mellitus: A Disproportionality Analysis Based on the FAERS. (PubMed, In Vivo) - "This study suggests that some DPP4is, including linagliptin, sitagliptin and vildagliptin, are associated with AKI, even without concomitant use of an AKI inducer. Given the widespread use of DPP4is and the severity of AKI, clinicians should be sufficiently informed about their potential relationship."

Journal • Acute Kidney Injury • Diabetes • Metabolic Disorders • Nephrology • Renal Disease

Efficacy and safety of anagliptin added to metformin and empagliflozin 25 mg in patients with type 2 diabetes: a 24-week randomized, double-blind, placebo-controlled phase 3 trial with 28-week open-label extension. (PubMed, Diabetes Res Clin Pract) - "In this first placebo-controlled trial evaluating DPP-4 inhibitor addition to maximally dosed empagliflozin (25 mg) plus metformin, anagliptin significantly improved glycemic control and β-cell function with a favorable safety profile, supporting this triple combination as an effective intensification strategy."

Clinical • Journal • P3 data • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Glycemic Variability of Combination Therapies in T2DM (clinicaltrials.gov) - P4 | N=178 | Recruiting | Sponsor: JW Pharmaceutical

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

Safety of anagliptin/metformin combination tablets evaluated by non-inferiority between pre- and post-serum lactic acid levels in Japanese patients with type 2 diabetes and moderate renal impairment (AMELIO STUDY). (PubMed, J Diabetes Investig) - "This study demonstrates that the fixed-dose combination of anagliptin and metformin can be used safely in patients with type 2 diabetes complicated by moderate renal dysfunction. The advantage of this fixed-dose combination is also considered to be very large."

Head-to-Head • Journal • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Endogenous GIP signaling is indispensable for DPP-4 inhibitor-mediated metabolic control in mice. (PubMed, J Diabetes Investig) - "Endogenous GIP signaling is essential for both glucose-lowering and anti-obesity actions of DPP-4 inhibitors in mice. GLP-1 elevation alone is insufficient to compensate for GIP receptor deficiency. These findings refined the mechanistic understanding of DPP-4 inhibitors, highlighted the physiological importance of GIP, and suggested context-dependent metabolic actions of incretins."

Journal • Preclinical • Genetic Disorders • Obesity

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