Januvia (sitagliptin) / Ono Pharmaceutical, Merck (MSD) - LARVOL DELTA

Phase I/Ib study of inavolisib (INAVO) alone and in combination with endocrine therapy ± palbociclib (PALBO) in patients (pts) with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced/metastatic breast cancer (HR+, HER2– LA/mBC): Analysis of hyperglycemia (HG) in prediabetic/obese pts. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT03006172 Background: INAVO, a highly potent and selective PI3Kα inhibitor that also promotes degradation of mutated p110α, is approved by the FDA in combination with PALBO + fulvestrant (FULV) for PIK3CA-mutated, HR+, HER2–, endocrine-resistant advanced BC... Adults ≥ 18 years of age received INAVO alone (Arm A), + letrozole (LET) + PALBO (Arm B), + LET (Arm C), + FULV (Arm D), + FULV + PALBO (Arm E), or + FULV + PALBO + primary prophylactic metformin (Arm F)...The most common anti-HG medications were metformin (52.7%; biguanide; concomitant use in Arm F excluded), empagliflozin (25.5%; SGLT-2 inhibitor), sitagliptin (22.7%; DPP-4 inhibitor), and pioglitazone (13.6%; thiazolidinedione); insulin was used in 8.2% of pts... A high proportion of prediabetic/obese pts were included in GO39374. In most of these pts, HG was manageable with dose interruptions and oral anti-HG medications, most commonly metformin. Data support the use..."

Clinical • Combination therapy • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Obesity • Oncology • Solid Tumor • HER-2 • PIK3CA

Risk of prostatitis in patients with type 2 diabetes mellitus: An observational retrospective cohort study of canagliflozin versus other antihyperglycemic agents using propensity score matching. (PubMed, PLoS One) - "This analysis found no evidence of a statistically significantly increased risk of prostatitis among adult male patients with T2DM receiving canagliflozin compared with the other AHAs evaluated in this study."

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

Sequential exposure to anoxic/oxic conditions leads to biotransformation and reduced sitagliptin toxicity in urban hyporheic zones. (PubMed, J Hazard Mater) - "All investigated transformation products exhibited lower cytotoxicity and oxidative stress responses than sitagliptin in in vitro bioassays, highlighting the toxicity reducing potential of the hyporheic zone. By identifying conditions that promote sitagliptin transformation and characterizing its transformation products toxicologically, our work provides parameters for enhanced sitagliptin removal in aquatic environments and improved risk assessment of fluorinated trace organic contaminants."

Journal

SITAGLIPTIN FOR PREVENTION OF ACUTE GVHD AFTER HAPLO-IDENTICAL PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (EBMT 2026) - "In this study, patients who were pending to undergo PBSCT from an halo-identical donor were randomly allocated to high dose post-transplant cyclophosphamide, cyclosporine A and mycophenolate mofetil with (treatment arm) or without siglistatin (control arm) in a ratio of 2:1. The interim analysis of our clinical trial indicates that the addition of sitagliptin to the standard aGVHD prophylaxis regimen may reduce the incidence of aGVHD; the observed effect is clinically meaningful but attains only borderline statistical significance. These findings are constrained by the presently small sample size and short follow-up, therefore awaits continued patients enrollment and extended observation."

Acute Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • Septic Shock • Severe Hypoglycemia • Transplantation • CD34

TRED: Triple Hypoglycemic Regimens In Patients With Newly Diagnosed Type 2 Diabetes Mellitus (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: Second Affiliated Hospital of Guangzhou Medical University

New P1/2 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Research on the Anti-Glioma Efficacy of Sitagliptin (ChiCTR) - P=N/A | N=30 | Not yet recruiting | Sponsor: The Affiliated Hospital of Xuzhou Medical University; The Affiliated Hospital of Xuzhou Medical University

New trial • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

Comparative Effectiveness of Oral Semaglutide vs Sitagliptin Among Individuals With Heart Failure With Preserved Ejection Fraction (STEP-HFpEF DM ORAL) (clinicaltrials.gov) - P=N/A | N=20000 | Active, not recruiting | Sponsor: Brigham and Women's Hospital

HEOR • New trial • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

Anti-Diabetic Medications to Fight PD and LBD (clinicaltrials.gov) - P4 | N=18 | Completed | Sponsor: Mayo Clinic | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Dementia • Lewy Body Disease • Movement Disorders • Parkinson's Disease

Mechanistic insights into sitagliptin-induced skin autoimmunity: Linking environmental drug exposure to IL-6 activation in bullous pemphigoid. (PubMed, Ecotoxicol Environ Saf) - "This study provides the first mechanistic evidence linking sitagliptin exposure to BP via IL-6-mediated immune dysregulation. Our findings highlight the potential dermatotoxic and immunotoxic risks of pharmaceutical contaminants in the environment and underscore the importance of integrating network toxicology with experimental approaches for environmental health risk assessment."

Journal • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology • IL17A • IL6

Neo-CD: Neoadjuvant Chemotherapy, Anti-PD-1 Antibody and Sitagliptin for Locally Advanced pMMR CRC (clinicaltrials.gov) - P1/2 | N=138 | Not yet recruiting | Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

New P1/2 trial • pMMR • Colorectal Cancer • Oncology • Solid Tumor

Sitagliptin Potentiates the Anticancer Activity of Doxorubicin Through ROS-Driven Apoptosis and MMP/TIMP Regulation in HeLa Cells. (PubMed, Pharmaceutics) - "The combination exhibits a clear synergistic effect and demonstrates strong potential as a supportive therapeutic strategy. These findings warrant further in vivo and clinical-level investigations to evaluate the translational applicability of sitagliptin in cervical cancer therapy."

Journal • Cervical Cancer • Diabetes • Metabolic Disorders • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • AKT1 • ANXA5 • CASP8 • CASP9 • MAPK1 • MMP1 • MMP2 • TIMP1 • TIMP2

Unlocking the catalytic potential of transaminase: A two-decade evolution toward green and scalable biocatalysis. (PubMed, Bioorg Chem) - "Although these enzymes are now regularly used in industry for the synthesis of Sitagliptin, Mexiletine, Dolutegravir, etc., there is still scope for improvement involving challenges such as equilibrium thermodynamics, co-product removal, limited substrate tolerance, and scope. This review focuses on the detailed use of these enzymes in the pharmaceutical industry over the past 20 years and comprehensive approaches encompassing protein and equilibrium engineering, immobilization, continuous-flow biocatalysis, smart donors, and multi-enzymatic cascades, which have been and are being used for their evolution into the pharmaceutical industry."

Journal • Review

GLIMSI: A real-world, multicenter study assessing the effectiveness and safety of Sitagliptin + Glimepiride + Metformin FDC in Indian patients with Type 2 diabetes. (PubMed, PLoS One) - "The triple-combination therapy (sitagliptin, glimepiride, and metformin) demonstrated superior efficacy in achieving glycemic control, as evidenced by significant reductions in HbA1c, fasting blood glucose (FBG), and postprandial plasma glucose (PPG). Furthermore, the therapy facilitated meaningful weight reduction, highlighting its clinical utility as a comprehensive therapeutic option for managing glycemic parameters in both T2DM with overweight and normal-weight patients."

Clinical • Journal • Observational data • Real-world evidence • Retrospective data • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Circadian fluctuation of soluble CD26 dictates the impact of the timing of cord blood transplantation on acute graft-versus-host disease. (PubMed, Nat Commun) - "Inhibiting the enzymatic activity of sCD26 with Sitagliptin significantly mitigated aGVHD and improved survival in late-infused female mice. Our study indicates that scheduling UCB transplantation in the early morning could be a simple and effective prophylactic strategy for aGVHD and that inhibiting sCD26 could be a promising therapeutic approach for late infusions."

Journal • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Transplantation • DPP4

Beyond glycemic control: the cardiac and hepatic benefits of SGLT2 and DPP-4 inhibitors in mitigating chronic cadmium-induced inflammation, oxidative/nitrative stress, apoptosis and fibrosis. (PubMed, Front Physiol) - "This study aims to contrast the protective effects of "Canagliflozin; Cana" versus "Sitagliptin; Sita" in countering the chronic Cd-induced cardiac and hepatic damage. Both medications showed comparable cardio-hepatic protective effects. Yet, Cana outperformed Sita as a potentially effective therapy to counteract the negative consequences of chronic Cd-induced cardiac and hepatic pathologies."

Journal • Fibrosis • Immunology • Inflammation • Oncology • CASP3 • IL10 • NFKB1 • NOTCH1 • SMAD3 • SMAD7 • TNFA

Randomized controlled study on the impact of Xiaoke Wan compared with sitagliptin combined with metformin on blood glucose fluctuation in male patients with type 2 diabetes mellitus complicated with erectile dysfunction (ChiCTR) - P=N/A | N=84 | Not yet recruiting | Sponsor: Southern Medical University Southern Hospital; Southern Medical University Southern Hospital

New trial • Diabetes • Erectile Dysfunction • Metabolic Disorders • Type 2 Diabetes Mellitus

A Single-Center Phase II Clinical Study on the Use of the DPPIV Inhibitor Sitagliptin Phosphate (JANUVIA®) for the Prevention of Acute Graft-versus-Host Disease in Patients Undergoing Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation (ChiCTR) - P2 | N=70 | Recruiting | Sponsor: The First Affiliated Hospital of USTC; The First Affiliated Hospital of USTC

New P2 trial • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Myelodysplastic Syndrome • Transplantation

Medication Adherence in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). (PubMed, Diabetes Care) - "Medication adherence was consistently high in GRADE. Observed treatment group differences were small and of unclear clinical significance. Overall, lower adherence robustly predicted worsening glycemic control, highlighting the importance of ongoing assessment."

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

Antidiabetic DPP4 inhibitor Attenuates Intervertebral Disc Degeneration via Macrophage-Nucleus Pulposus Cell Crosstalk. (PubMed, Br J Pharmacol) - "DPP4 was a causal driver of IVDD, and its inhibition by sitagliptin mitigated degeneration by disrupting the pathogenic positive feedback loop between macrophages and NP cells. These findings reposition sitagliptin, a clinically approved antidiabetic drug, as a promising therapeutic candidate for IVDD, highlighting the translational potential of targeting DPP4 and its downstream inflammatory cascades."

Journal • Back Pain • Diabetes • Lumbar Back Pain • Metabolic Disorders • Musculoskeletal Pain • Pain • DPP4 • IL1B • NLRP3

Trends in Adverse Event Reports of Dipeptidyl Peptidase-4 Inhibitor-Associated Pemphigoid in Japan. (PubMed, Drugs Real World Outcomes) - "The number of reported DPP-4 inhibitor-associated pemphigoid events increased after the revised precautions of package inserts for DPP-4 inhibitors were released."

Adverse events • Journal • Diabetes • Immunology • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparative Effect of SGLT2 Inhibitors and GLP-1 Agonists on Glycemic Control in Type 2 Diabetes Mellitus. (PubMed, J Pharm Bioallied Sci) - "They were randomly given either empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin, Bexagliflozin, Sotagliflozin (an SGLT2 inhibitor) or liraglutide, Sitagliptin, Saxagliptin, Linagliptin, Alogliptin, Vildagliptin (n GLP-1 receptor agonist) to consume for 24 weeks. But GLP-1 agonists are better at helping people lose weight and keep their hearts healthy, so they are also a fantastic choice for people who have these problems. It's crucial to consider what each patient needs and what could go wrong while establishing treatment plans for them."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Intelligent drug delivery-wound healing integrated hydrogel dressing for Type 2 Diabetes Mellitus wounds with wound microenvironment modulation. (PubMed, Biomaterials) - "This hydrogel is capable of responsively releasing the blood glucose-regulating drug (sitagliptin (Sit)) and, in accordance with the inflammatory condition, it dispenses the anti-inflammatory drug nimesulide (Nim) on demand. Immunohistochemical analyses confirmed the hydrogel's efficacy in substantially decreasing IL-6 levels (25.7 %) and augmenting CD31 expression (315.3 %). Collectively, this intelligent hydrogel dressing holds immense promise for the treatment of diabetic wounds."

Journal • Diabetes • Infectious Disease • Metabolic Disorders • Type 2 Diabetes Mellitus • CD31 • IL6 • PECAM1

Effects of Short-Term Intensive Insulin Therapy Combined With Oral Hypoglycemic Agents for Inducing Remission in Newly Diagnosed Type 2 Diabetes Mellitus: A Randomized Clinical Trial. (PubMed, J Diabetes) - "Oral hypoglycemic agents facilitated SIIT implementation and enhanced transient improvements in glycemic control. However, similar 12-month diabetes remission rates suggest prolonged sequential therapy may be needed for sustained glycemic benefit."

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

Cardiovascular Disease and Diabetes: A New Challenge in the Treatment and Management. (PubMed, Int J Mol Sci) - "The latest classes of glucose-lowering drugs introduced in the clinical practice are DPP4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin, and alogliptin), GLP-1 receptor agonists (semaglutide, liraglutide, albiglutide, dulaglutide, exenatide, and lixenatide), and SGLT-2 inhibitors (empaglifozin, canaglifozin, and dapaglifozin). Multiple lines of evidence show that all these new drugs associated with the treatment of diabetic disease have the same effectiveness as the traditional antidiabetic drugs, and excellent cardiovascular safety, highlighting their potential in significantly reducing major cardiovascular events and mortality. The aim of our review is to summarise the clinical efficacy of these recently introduced drugs to optimise treatment strategies, especially in the early phase of diabetic disease."

Journal • Review • Cardiovascular • Diabetes • Metabolic Disorders

Topical Administration of Sitagliptin Prevents Retinal Neurodegeneration in a Model of Glaucoma Induced by Dexamethasone. (PubMed, Int J Mol Sci) - "Glaucoma was induced in mice by periocular injection of dexamethasone (DEX) once weekly for five weeks. Furthermore, it suppressed overexpression of galectin-3 and gamma-synuclein in the optic nerve head (ONH) (p < 0.001), key mediators of inflammation and apoptosis. Sitagliptin eye drops exert a potent neuroprotective effect against corticosteroid-induced glaucoma, supporting their potential as a novel therapeutic strategy for glaucoma."

Journal • CNS Disorders • Diabetes • Glaucoma • Inflammation • Metabolic Disorders • Ophthalmology • Solid Tumor • LGALS3