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anagliptin + metformin (SK 1501 / Metoana / SK1501)

✓ Approved

Sanwa Kagaku Kenkyusho Co., Ltd. · DPP4 · Small Molecule

What is anagliptin + metformin?

anagliptin + metformin is a small molecule developed by Sanwa Kagaku Kenkyusho Co., Ltd.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesSK 1501, Metoana, SK1501
CompanySanwa Kagaku Kenkyusho Co., Ltd.
Drug ClassSmall Molecule
Molecular TargetDPP4
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Sanwa Kagaku Kenkyusho Co., Ltd.

Mechanism of Action

Molecular Targets

anagliptin + metformin acts on 1 molecular target:

DPP4dipeptidyl peptidase 4 (CD26, DPPIV)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

anagliptin + metformin is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Metabolism and nutrition disordersType 2 diabetes mellitus✓ Approved

Related Research Articles

PubMedInternational immunopharmacology2026-08-30

Targeting the macrophage-NLRP3 inflammasome-pyroptosis axis: Metformin-capped silver nanoparticles as a novel therapy for premature ovarian insufficiency.

Feng Sifang S, Zhao Juan J, Li Peixuan P, Yang Ting T et al.

The paracrine crosstalk between macrophages and granulosa cells, forming a "macrophage M1 polarization-inflammation-pyroptosis" vicious cycle in the ovarian immune microenvironment, promotes premature ovarian insufficiency (POI) progression. This study aimed to investigate the therapeutic potential of metformin-capped silver nanoparticles (Met-AgNPs) in disrupting pathological paracrine signaling axis and restoring ovarian function. Met-AgNPs and control AgNPs were synthesized and physicochemically characterized. Dynamic light scattering (DLS) was conducted to evaluate the hydrodynamic diameter, polydispersity index (PDI), and zeta potential of the nanoparticles in different dispersion media (deionized H2O, PBS, DMEM). The in vitro release kinetics and in vivo biodistribution were also evaluated. THP-1-derived macrophages were induced to M1 polarization and treated with Met-AgNPs, AgNPs, or metformin, followed by assessment of macrophage polarization states. The conditioned medium (CM) from these macrophages was then applied to human granulosa KGN cells to evaluate its effects on NLRP3 inflammasome activation and pyroptosis. A cyclophosphamide (CTX)-induced POI rat model was established and treated with Met-AgNPs, AgNPs, or metformin. Ovarian function was evaluated via estrous cycle, hormone levels, follicle counting, and fertility assessment. Ovarian histopathology, macrophage polarization, inflammation, and NLRP3-driven pyroptosis were assessed. Met-AgNPs exhibited a spherical morphology, smaller hydrodynamic diameter, and enhanced colloidal stability compared to AgNPs. Crucially, Met-AgNPs demonstrated sustained drug release and achieved targeted accumulation with localized retention in inflamed ovaries. In vitro, treatment with Met-AgNPs, AgNPs, or metformin all reprogrammed M1 macrophages towards M2 phenotype, accompanied by decreased pro-inflammatory cytokine secretion and increased anti-inflammatory cytokine secretion. The CM from all treated macrophages inhibited NLRP3 inflammasome activation and pyroptosis in KGN cells. Notably, Met-AgNPs demonstrated superior efficacy among all treatment groups. In POI rats, Met-AgNPs treatment restored estrous cycles, serum hormone levels, and healthy follicle count, and improved fertility. These improvements were mechanistically associated with the inhibition of M1 macrophage infiltration and NLRP3-driven pyroptosis within the ovarian tissues. Met-AgNPs ameliorated POI by reprogramming macrophage polarization from M1 to M2 phenotype and then inhibiting NLRP3-dependent pyroptosis in granulosa cells. Our findings propose Met-AgNPs as a promising nanotherapeutic strategy for alleviating ovarian inflammation and restoring fertility in POI.

PMID 42669281
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PubMedFrontiers in oncology2026-08-29

Metformin modulates the phenotypes of tumor-associated macrophages in glioblastoma in a context-dependent manner by promoting the homeostasis of macrophages.

Das Ashish A, Mahfooz Sadaf S, Wang Fei F, Guan Bingjie B et al.

Glioblastoma (GBM) remains the most aggressive primary adult brain cancer attributed to its immunosuppressive nature. Radiation therapy (RT) and concurrent temozolomide chemotherapy are the standard treatments for GBM. Emerging evidence indicates that metformin has potential as an anti-tumor agent that can reshape the immune landscape across various malignancies. We thus postulate that metformin may enhance the anti-tumor effect of RT by modulating the immunosuppressive milieu in GBM. We first explore multiple in vitro conditions, with or without pre-induction, and mimicked a tumor microenvironment to demonstrate a highly context-dependent effect of metformin on the polarization of bone marrow-derived macrophages (BMDMs). We then investigated the antitumor activity and immune-modulatory effects of metformin in combination with RT in GBM-bearing mice. The in vitro experiment showed that metformin inhibited the immunosuppressive effects of IL-4/IL-13 but also the immunostimulatory effects of Lipopolysaccharide (LPS) on BMDMs, demonstrating bidirectional immunomodulatory properties that depend on the baseline inflammatory stimulus. In tumor cell co-culture environment, metformin exhibited context-dependent immunoregulatory effects, predominantly promoting M1-associated activation. Notably, concurrent metformin treatment counteracted M2 polarization typically induced by the tumor microenvironment. In a high m-MCSF inducted M2-dominated condition, metformin preferentially shifted the highly polarized M2 phenotype toward an M1-like state in a time and dose-dependent manner but with limited promotion of M1 subtype maturation. RNAseq results on BMDM treated with metformin showed increased homeostasis. Metformin showed dose-dependent immunomodulatory effects when combined with RT in vitro. In syngeneic GBM mouse models, concurrent metformin + RT significantly prolonged survival and reduced tumor burden by reprogramming tumor-associated macrophages (TAMs), elevating intratumoral CD8+ T-cell infiltration and the CD8+/Treg ratio, increasing circulating CD8+ T cells, reversing RT-induced expansion of monocytic myeloid-derived suppressor cells (mMDSCs), and expanding CD4+ and CD8+ effector memory populations in peripheral blood. Metformin demonstrates inhibitory effects on M2 phenotype of macrophages. However, it is not a simple M2 inhibitor; instead, it functions primarily as a neutralizer of highly polarized macrophage states by promoting transcriptomic homeostasis. This context-dependent activity enables metformin to relieve the profoundly immunosuppressive TME of GBM to potentiate the anti-tumor effects of RT and by enhancing systemic immune memory.

PMID 42666173
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PubMedPharmacological research2026-08-29

Heterogeneous Associations of Antidiabetic Medications with Cancer Prognosis: Evidence from 61 Studies with Over 1.1 Million Patients.

Luo Peng P, Ding Yanxi Y, Huang Weiye W, Ma Wen W et al.

This systematic review and meta-analysis aimed to comprehensively evaluate the prognostic impacts of seven classes of antidiabetic medications in patients with cancer, predominantly in the setting of concomitant type 2 diabetes mellitus (T2DM), and to elucidate their potential differential effects. A systematic search of PubMed, Embase, Cochrane Library, and the Web of Science was conducted from inception to May 2025, utilizing keywords including "antidiabetic drugs," "cancer," and "prognosis." Based on predefined criteria, eligible English-language randomized controlled trials and cohort studies were included if they compared the prognostic impacts of metformin, insulin, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and thiazolidinediones in patients with cancer. The primary outcome domain was all-cause survival, represented by all-cause mortality (ACM) or overall survival (OS) according to the terminology of the original studies. Secondary cancer-related outcomes included cancer-specific mortality (CSM), disease-free survival (DFS), progression-free survival (PFS), and recurrence-free survival (RFS). Multiple independent investigators performed data extraction and quality assessment. Statistical analyses were performed using OnlineMeta V1.1. DerSimonian-Laird random-effects models were used for all primary meta-analyses to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), while fixed-effects estimates were examined as complementary sensitivity analyses. Study quality was assessed using the Newcastle-Ottawa Scale and the Cochrane risk-of-bias tool for randomized trials. A total of 61 studies comprising 1,106,966 patients with cancer were included. Metformin use was associated with lower ACM (HR=0.82, 95% CI: 0.74-0.91, P=0.0001) and CSM (HR=0.77, 95% CI: 0.69-0.87, P<0.0001), whereas insulin use was associated with higher ACM (HR=2.03, 95% CI: 1.63-2.51, P<0.0001). Among the drug classes analyzed, SGLT2 inhibitor use showed a nonsignificant inverse trend with ACM (HR=0.44, 95% CI: 0.11-1.71, P=0.24) and was associated with lower CSM (HR=0.21, 95% CI: 0.20-0.22, P<0.0001), although these estimates were based on few observational studies with study-specific comparator groups and do not establish superiority over other drug classes. In adjusted-HR-only sensitivity analyses, the direction of association was generally consistent for the major metformin outcomes and insulin-related ACM, whereas several other comparisons were attenuated or could not be pooled because too few studies reported adjusted estimates. This meta-analysis identified heterogeneous associations between antidiabetic drug use and cancer-related survival outcomes, with variation across drug classes, cancer types, and study-level mean age groups. Because the evidence was derived predominantly from observational studies with study-specific comparator groups, substantial between-study heterogeneity, and limited data for newer agents, the pooled estimates should not be interpreted as evidence of treatment superiority or used to rank drug classes. These findings are hypothesis-generating and warrant confirmation in prospective studies using clinically comparable treatment groups, standardized outcome definitions, and rigorous control of confounding.

PMID 42668074
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PubMedJournal of molecular histology2026-08-29

Schisandra chinensis polysaccharide attenuates diabetic islet cell injury by promoting autophagy via suppression of the PI3K/AKT/mTOR signaling cascade.

Zhou Xiao-Ying XY, Zhou Guang-Hui GH, Li Wen-Chong WC, Zhang Jun-Feng JF et al.

Schisandra chinensis polysaccharide (SCP) has demonstrated antidiabetic properties in previous studies; however, the mechanisms underlying its regulation of autophagy in pancreatic protection remain poorly understood. This study investigated how SCP modulates autophagic pathways to alleviate diabetic pathology. Diabetic rats were administered SCP orally, followed by histopathological and biochemical assessments of pancreatic islet function and tissue damage. Beta-TC-6 pancreatic β-cells were exposed to SCP to evaluate cellular viability, insulin secretion, and autophagic processes using immunohistochemistry, Western blotting, immunofluorescence, and transmission electron microscopy. SCP dose-dependently attenuated diabetes-associated weight loss, reduced hyperglycemia, and improved β-cell function. Histological examination revealed amelioration of pancreatic islet disorganization, diminished collagen deposition, and reduced basement membrane thickening. Mechanistically, SCP enhanced autophagic activity in pancreatic tissues and Beta-TC-6 cells by inhibiting the PI3K/AKT/mTOR signaling cascade, with high-dose SCP exhibiting efficacy comparable to that of metformin. Chloroquine co-treatment abolished these effects, confirming autophagy dependence. This study demonstrates that SCP alleviates diabetes by restoring β-cell function and inducing protective autophagy via the inhibition of the PI3K/AKT/mTOR pathway. These findings indicate SCP as a potential candidate for diabetes therapy.

PMID 42667464
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PubMedTissue & cell2026-08-29

Mechanism of Gegen Qinlian Decoction in the treatment of diabetic cataract based on network pharmacology and experimental validation.

Xia Juanjuan J, Wang Xin X, Fu Xiaomei X, Zhong Weihong W et al.

Diabetic cataract (DC) is one of the most common complications of diabetes mellitus, currently lacks effective treatments. Gegen Qinlian Decoction (GQD) is effective against diabetes and its complications, but its efficacy and mechanism against diabetic cataracts remain unclear. In this study, the effects and mechanisms of GQD in treating diabetic cataracts were evaluated in Zucker diabetic fatty (ZDF) rats. All rats were randomly divided into control, model, low/high-dose GQD and metformin groups. Each group was administered the drug or an equal volume of distilled water for 12 weeks. Fasting blood glucose and body weight were measured every two weeks. At the end of the experiment, the degree of lens opacity was examined. Pathological changes in the lenses were observed by hematoxylin-eosin staining. The contents of soluble proteins, malondialdehyde (MDA), superoxide dismutase (SOD) and sorbitol were measured in the lenses. Network pharmacology was employed to predict the signaling pathways of GQD in treating DC. Additionally, the protein expressions of p38, JNK and their phosphorylation levels were evaluated by Western blot. The results showed that GQD significantly alleviated lens opacity, reduced sorbitol accumulation and ameliorated oxidative stress in rats with DC. Network pharmacology revealed that the MAPK signaling pathway is a key regulatory pathway of GQD against DC. Western blot results further confirmed that GQD significantly downregulated the phosphorylation levels of p38 and JNK in the lenses of rats with DC.This study implicates GQD as a potential therapeutic candidate for DC.

PMID 42667784
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PubMedInternal and emergency medicine2026-08-29

Antidiabetic medications and arterial thrombotic risk reduction: a narrative review.

Santilli Francesca F, Simeone Paola P, Liani Rossella R

Diabetes mellitus is associated with a persistent prothrombotic state driven by platelet hyperreactivity, endothelial dysfunction, oxidative stress, and chronic low‑grade inflammation, all of which contribute to increased cardiovascular (CV) risk. Importantly, a substantial residual thrombotic risk persists even with optimal glycemic control, indicating that glucose lowering alone is insufficient to prevent vascular complications. In this context, antidiabetic therapies have emerged as important modulators of CV risk beyond their metabolic effects. Several drug classes-including metformin, thiazolidinediones, DPP‑4 inhibitors, SGLT‑2 inhibitors, and GLP‑1 receptor agonists-have been shown to influence platelet activity, endothelial function, and inflammatory pathways. These effects are mediated through mechanisms such as enhanced nitric oxide bioavailability, reduced oxidative stress, attenuation of platelet activation, and modulation of vascular inflammation. Among these, GLP‑1 receptor agonists exert particularly pronounced effects on endothelial function, oxidative stress, and platelet reactivity, alongside robust reductions in CV events. More broadly, accumulating experimental and clinical evidence indicates that several antidiabetic agents exert clinically meaningful antithrombotic actions, contributing to decreased rates of major CV events and heart failure. However, these benefits vary across drug classes and patient populations. This highlights the importance of an individualized therapeutic approach in type 2 diabetes, where treatment selection should account not only for glycemic targets but also for CV and thrombotic risk. Choosing agents with proven CV benefit may optimize overall risk reduction and improve long‑term outcomes. This narrative review aims to critically examine the available experimental and clinical evidence on the effects of antidiabetic drugs on platelet function, thrombosis, and thrombo-inflammatory pathways, highlighting the mechanisms that may contribute to cardiovascular protection beyond glucose lowering.

PMID 42667518
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