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

Machine learning prediction, molecular dynamics simulation, and in vitro studies of putative leads from citrus essential oil metabolites as potential dipeptidyl peptidase-4 inhibitors. (PubMed, Comput Biol Med) - "Of the six CEOs investigated, only Citrusreticulata (18.21 μg/mL) had lower half maximal inhibitory concentration (IC50) than the reference standard [sitagliptin (22.88 μg/mL)]...Findings from this study show that relative abundance of metabolites does not directly translate into their biological activities and CEOs and their metabolites, especially beta-terpineol, possess potential anti-DPP4 effects. Nevertheless, further studies such as in vivo validation and lead optimization are necessary to fully establish the antidiabetic potential of the investigated CEOs and their metabolites."

Journal • Preclinical

Properties of AgNPs stabilized with polyvinylpyrrolidone relevant to antidiabetic agents. (PubMed, Nanoscale) - "In vivo studies showed that AgNPs inhibited α-amylase, α-glucosidase, and dipeptidyl peptidase-4, up to 3.51, 3827.76, and 11 times more effective than acarbose and sitagliptin, respectively. Advanced glycation end products inhibition by AgNPs was up to 61.4 times higher than metformin. In vivo experiments revealed that AgNPs antihyperglycemic activities were close to acarbose, while the same hypoglycemic effect was achieved with AgNP doses up to 167 times lower than that of glibenclamide. The results show the possibility to decrease the glibenclamide dose by two orders, that indicates high AgNP perspective to reduce drug toxicity and side effects."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Henoch-Schönlein purpura induced by sitagliptin: A case report. (PubMed, SAGE Open Med Case Rep) - "Sitagliptin was discontinued, and the patient was treated with celecoxib, colchicine, and cefadroxil for wound infection. However, urinalysis revealed new 0.3 g/L protein. Overall, this case highlights a new potential association of dipeptidyl peptidase-4 inhibitors with Henoch-Schönlein purpura, which may have systemic consequences."

Journal • Diabetes • Infectious Disease • Metabolic Disorders • Type 2 Diabetes Mellitus • Vasculitis

Repurposing DPP-4 inhibitors as anticancer agents in KRAS-mutated pancreatic ductal adenocarcinoma. (PubMed, BMC Pharmacol Toxicol) - "Overall, we report that Sitagliptin and Linagliptin have significant anticancer potential towards KRAS-mutated PDAC. Furthermore, we recommend repurposing of more drugs to examine their anti-cancer potential towards these aggressive cancers and to overcome clinical resistance in the near future."

Journal • Diabetes • Metabolic Disorders • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Type 2 Diabetes Mellitus • KRAS • MIA

Dipeptidyl Peptidase 4 Inhibitors: Novel Therapeutic Agents in the Management of Type II Diabetes Mellitus. (PubMed, Pharmacoepidemiol Drug Saf) - "DPP-4 inhibitors remain effective and well-tolerated options for managing T2DM."

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

From Separation to Safety Prediction: Validated RP-HPLC Method for Simultaneous Estimation of Sitagliptin and Lobeglitazone, LC-MS/MS Identification of Degradant Products, and In Silico Safety Profiling. (PubMed, Biomed Chromatogr) - "In silico ADMET and toxicity profiling predicted high gastrointestinal absorption for all degradation products, with PI-1 and PI-2 flagged for carcinogenicity and all except PI-3 showing nephrotoxicity. This integrated analytical-computational approach provides a reliable tool for quality control and safety assessment of this antidiabetic formulation."

Journal • Diabetes • Metabolic Disorders

Dual-source DPP4 drives intestinal fibrosis in Crohn's disease: synergistic therapeutic targeting of host and microbiota pathways. (PubMed, Gut Microbes) - "Furthermore, pharmacological inhibition of host DPP4 (sitagliptin) or selective blockade of mDPP4 (Dau-d4) attenuated fibrosis in murine models, with combined therapy showing enhanced efficacy. These findings underscore the roles of DPP4, originating from both host and microbiota, and existing in membrane-bound and soluble forms, in promoting CD-associated intestinal fibrosis. This study identifies DPP4 as a novel therapeutic target, proposing dual-source inhibition as a promising strategy to prevent stricture formation in CD patients, thereby addressing a critical unmet clinical need."

Journal • Crohn's disease • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • DPP4

Metabolic reprogramming of CD8+ T-Cells by DPP-4 inhibition for glioblastoma immunotherapy (SNO 2025) - "The functional and metabolic reprogramming of CD8+ T cells were in part mediated by activation of glutamate decarboxylase (GAD), which feeds glutamate into the TCA cycle, and pharmacological inhibition of GAD mitigated sitagliptin-mediated T cell proliferation...In summary, we show that pharmacological inhibition of DPP-4 promotes anti-tumorigenic function of CD8+ T-cell by prolonging effector function through metabolic reprograming. These findings support future translational efforts to repurpose DPP-4 inhibitors as immunotherapy agents for GBM and other cancers that are characterized by T cell dysfunction."

IO biomarker • Brain Cancer • Diabetes • Glioblastoma • Metabolic Disorders • Solid Tumor • Type 2 Diabetes Mellitus • CD8

Targeting macrophage migration inhibitory factor: A phase 2 and pharmacodynamic study of sitagliptin in patients with progressive grade 4 gliomas (SNO 2025) - P1 | "A trial (NCT02669173) performed at the Cleveland Clinic demonstrated that pre-surgical anti-MDSC therapy (capecitabine) was associated with reduced circulating MDSCs and increased cytotoxic immune infiltration in tumor tissue. Secondary endpoints: PFS6, OS12, safety. Exploratory endpoints: peripheral and intratumoral immune profiling for assessment of TAMs, MDSCs, and CD8+ T cells; tumor radiomic features on MRI brain pre-surgery predictive of intratumoral and peripheral CD8+ T cell count and peripheral MDSC levels; peripheral blood cytokine and immune gene expression profiling for increase in immune activation signatures;"

Clinical • P2 data • PK/PD data • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • CD8 • MIF

Dipeptidyl peptidase-4 inhibitors and diabetic retinopathy in type 2 diabetes: A network meta-analysis of randomized clinical trials. (PubMed, J Diabetes Complications) - "Current randomized evidence indicates class-level neutrality of DPP-4 inhibitors on DR incidence, with no dose-response signal. Choice among gliptins may therefore be guided primarily by glycemic efficacy, safety, and participant characteristics rather than retinal risk."

Clinical • Journal • Retrospective data • Review • Diabetes • Diabetic Retinopathy • Metabolic Disorders • Retinal Disorders • Type 2 Diabetes Mellitus

Dipeptidyl Peptidase 4 Mediated Caspase-8 Affects Cognitive Impairment in Mice With Alzheimer's Disease. (PubMed, FASEB J) - "Similar results were observed after HT22 neurons were treated with Aβ25-35 and the DPP4 inhibitor sitagliptin (Sit). Moreover, the treatment with a Caspase-8 inhibitor (Z-LETD-FMK) showed that the inhibition of Caspase-8 inhibited the expression of NLRP3 and Caspase-1 in the AD model cells, but had no further inhibitory effect under the treatment of Sit. Our results suggest that DPP4 knockout may ameliorate learning and memory dysfunction in AD model mice by regulating pyroptosis and apoptosis pathways through Caspase-8."

IO biomarker • Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • BCL2 • BDNF • CASP3 • CASP8 • IL1B • NLRP3

Exploring the Evidence for Personalized Pharmacotherapy in Type 2 Diabetes-A Systematic Review. (PubMed, J Pers Med) - " We systematically searched PubMed, Scopus, and Web of Science for studies published from the earliest available records to 18 August 2025 using the following Boolean search terms: "miRNA AND gliclazide", "miRNA AND glibenclamide", "miRNA AND gliquidone", "miRNA AND glimepiride", "mirRNA AND metformin", "miRNA AND pioglitazone", "miRNA AND rosiglitazone", "miRNA AND sitagliptin", "miRNA AND vildagliptin", "miRNA AND alogliptin", "miRNA and saxagliptin", "miRNA AND linagliptin", "miRNA AND liraglutide", "miRNA and dulaglutide", "miRNA AND semaglutide", "miRNA AND tirzepatide", "miRNA AND lixisenatide", "miRNA AND empagliflozin", "miRNA AND dapagliflozin", miRNA AND insulin glargine", "miRNA AND insulin detemir", "miRNA AND insulin degludec", "miRNA AND..."

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

Triple arm, prospective, real-world study comparing the efficacy of FDC teneligliptin + dapagliflozin to FDC sitagliptin + dapagliflozin, and FDC linagliptin + empagliflozin in Indian type 2 diabetes mellitus patients using CGM device: the Amplify-TIR study. (PubMed, Cardiovasc Diabetol Endocrinol Rep) - No abstract available

Journal • Real-world evidence • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Sitagliptin does not interfere with VEGF-A signaling in retinal endothelial cells in vitro. (PubMed, Exp Clin Endocrinol Diabetes) - "The VEGF-A165-induced declines of the cell index and TJ-protein claudin-1 were prevented by tivozanib, and this process was not modulated by sitagliptin.The underlying mechanisms of barrier dysfunctions caused by sitagliptin or VEGF-A are different and independent. Most importantly, the DPP-4 inhibitor does not interfere with blocking VEGF signaling to correct VEGF-A-dependent barrier dysfunction."

Journal • Preclinical • Diabetes • Diabetic Macular Edema • Metabolic Disorders • Ophthalmology • Type 2 Diabetes Mellitus • CLDN1 • CLDN5

Common genetic variants near SLC2A2 and glycemic response to glimepiride in the GRADE comparative effectiveness clinical trial. (PubMed, medRxiv) - P3 | "We conducted a pharmacogenomic genome-wide association study (GWAS) in the Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness (GRADE) Study to identify genetic predictors of glycemic response to insulin glargine, glimepiride, liraglutide, and sitagliptin, when added to metformin in a diverse population. In conclusion, genetic variation influences glycemic response to medications, with SLC2A2 emerging as a key determinant of sulfonylurea response. Clinical Trial registration number: NCT01794143."

HEOR • Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • SLC2A2

MicroRNAs modulated by DPP-4 inhibitor and bedtime NPH insulin therapy in individuals with type 2 diabetes. (PubMed, Front Endocrinol (Lausanne)) - "To evaluate the effects of bedtime NPH insulin and sitagliptin on serum miRNA expression in individuals with type 2 diabetes (T2D), thirty-two patients with T2D inadequately controlled with metformin and glyburide were randomly assigned to an additional 6-month treatment with either bedtime NPH insulin or sitagliptin. Sitagliptin and bedtime NPH insulin induced metabolic improvement and distinct modulation of circulating miRNAs, with sitagliptin influencing a broader spectrum of miRNA expression. The upregulated miRNAs are involved in pathways related to insulin signaling, inflammation, and cellular homeostasis and support the hypothesis that sitagliptin exerts pleiotropic effects beyond glycemic control."

Clinical • Journal • Atherosclerosis • Cardiovascular • Diabetes • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • MicroRNA 30c • MIR193B • MIR27A • MIR320A • MIR660

In Vivo Inhibition of Dipeptidyl Peptidase 4 and Neprilysin Activity Enables Measurement of GLP-1 Secretion in Male Rats. (PubMed, J Endocr Soc) - "To investigate in vivo degradation of exogenous GLP-1, the neprilysin inhibitor (sacubitril 0.3 mg/kg) and the DPP-4 inhibitor (sitagliptin 10 mg/kg) were injected intravenously 15 minutes before IV administration of GLP-1(7-36)NH2 (2 pmol)...The peak of intact GLP-1 concentrations in response to oral glucose was 7-fold higher in inhibitor-treated rats compared to control rats, in which the GLP-1 response was barely detectable. Thus, in vivo inhibition of both DPP-4 and neprilysin activity stabilized newly secreted GLP-1, thereby enabling estimation of GLP-1 secretion in rats, which is otherwise notoriously difficult due to rapid degradation."

Journal • Preclinical

Pharmacological risks of khat-oral antidiabetic drug interactions among patients at Gondar university referral hospital. (PubMed, Sci Rep) - "Harmful khat-OAD interactions are common among T2DM patients in Northwest Ethiopia, primarily driven by behavioral and treatment-related factors, highlighting the need for culturally sensitive pharmacovigilance and patient education."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Addition of sitagliptin to ongoing metformin improved metabolic profile and pancreatic function via normalizing inflammatory cytokines' levels in patients with type 2 diabetes, a randomized double-blinded clinical trial. (PubMed, Expert Rev Endocrinol Metab) - "No significant changes were seen in HbA1c or vitamin D3. Sitagliptin plus metformin improved pancreatic function, glucose homeostasis, and reduced IL-1, IL-6, and IL-18 levels in T2DM patients with inadequate glycemic control on metformin alone, offering cardiovascular benefits (Clinical Trial Registration: https://www.irct.ir/trial/44061)."

Clinical • Journal • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • IL18 • IL6

Identifying potential drug targets for cerebral amyloid angiopathy: A Mendelian randomization study based on the druggable genes. (PubMed, Medicine (Baltimore)) - "Drug screening identified sitagliptin and zoledronic acid as potential DPP9-targeting compounds. This study provides genetic evidence identifying DPP9 as a potential drug target for CAA. The antidiabetic drug sitagliptin, predicted to bind DPP9 with high affinity, represents a promising candidate for therapeutic repurposing in CAA."

Journal • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Dementia • Hematological Disorders • DPP9

Metabolic reprogramming of CD8+ T-Cells by DPP-4 inhibition for glioblastoma immunotherapy (WFNOS 2025) - "The functional and metabolic reprogramming of CD8+ T cells were in part mediated by activation of glutamate decarboxylase (GAD), which feeds glutamate into the TCA cycle, and pharmacological inhibition of GAD mitigated sitagliptin-mediated T cell proliferation...In summary, we show that pharmacological inhibition of DPP-4 promotes anti-tumorigenic function of CD8+ T-cell by prolonging effector function through metabolic reprograming. These findings support future translational efforts to repurpose DPP-4 inhibitors as immunotherapy agents for GBM and other cancers that are characterized by T cell dysfunction."

IO biomarker • Brain Cancer • Diabetes • Glioblastoma • Metabolic Disorders • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • CD8

Targeting macrophage migration inhibitory factor: A phase 2 and pharmacodynamic study of sitagliptin in patients with progressive grade 4 gliomas (WFNOS 2025) - P1 | "A trial (NCT02669173) performed at the Cleveland Clinic demonstrated that pre-surgical anti-MDSC therapy (capecitabine) was associated with reduced circulating MDSCs and increased cytotoxic immune infiltration in tumor tissue. Secondary endpoints: PFS6, OS12, safety. Exploratory endpoints: peripheral and intratumoral immune profiling for assessment of TAMs, MDSCs, and CD8+ T cells; tumor radiomic features on MRI brain pre-surgery predictive of intratumoral and peripheral CD8+ T cell count and peripheral MDSC levels; peripheral blood cytokine and immune gene expression profiling for increase in immune activation signatures;"

Clinical • P2 data • PK/PD data • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • CD8 • MIF

Role of sitagliptin in diabetes-induced testicular damage via the Fas/FasL signalling pathway. (PubMed, Biotech Histochem) - "Basement membrane thickness, apoptotic cell and apoptotic tubul indexes, Fas, FasL, and caspase8 immunoreactivities were higher in diabetic groups compared to the control group, while no difference was found between the diabetic and sitagliptin groups. In conclusion, although 10 mg/kg sitagliptin reduced blood glucose levels in diabetes-induced hyperglycemia, it did not alter serum testosterone, FSH and LH levels, and did not appear to have a beneficial effect on diabetes-induced apoptosis and proliferation in the testes."

Journal • Diabetes • Metabolic Disorders • CASP8 • FASLG

Cardiovascular Sequel in Type-2 Diabetes Mellitus Patients on Various Dipeptidyl Peptidase-4 (DPP-4) Inhibitors: A Systemic Review and Meta-Analysis. (PubMed, Cureus) - "The systematic review and meta-analysis was conducted by utilizing widespread empirical research and randomized control trials (RCTs), evaluating sitagliptin, saxagliptin, alogliptin, and linagliptin. Sitagliptin and linagliptin appear neutral regarding HF risk. These findings highlight the importance of drug-specific evaluation when selecting a DPP-4 inhibitor for type-2 diabetic patients, particularly those having an elevated risk of heart failure."

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

Experimental and Computational Insights of a Benzytrietylammonium [CoBr4] Salt: A Potential Photocatalyst and Inflammation-Related Enzyme Inhibitor. (PubMed, ACS Omega) - "It also showed potent inhibitory effects on obesity-related enzymes such as lipase (IC50 = 41.93 μM) compared to orlistat (IC50 = 32.75 μM). Regarding diabetes-related targets, the complex effectively inhibited α-amylase (IC50 = 21.75 μM) in comparison to acarbose (ACR, IC50 = 18.08 μM), and promoted insulin signaling by inhibiting dipeptidyl peptidase-4 (DPP-4, IC50 = 22.01 μM) compared to sitagliptin (STG, IC50 = 4.07 μM)...A molecular docking approach was employed to investigate the binding affinities and molecular interactions of the two ligands forming the Co-(II) complex with several protein targets (PDB IDs: 3BAJ, 4A5S, 1LPB, 5MFA, and 1T49). The docking results revealed that the complex, through interactions such as hydrogen bonding, π-π stacking, carbon-hydrogen interactions, π-anion, π-cation, and π-alkyl interactions, exhibits promising inhibitory potential against the selected enzymes: α-amylase, dipeptidyl peptidase-4 (DPP-4), lipase, promyeloperoxidase..."

Journal • Diabetes • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • MPO • PTPN1