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metformin + sitagliptin (Januvia ER / Janumet ER / Janumet XR)

✓ Approved

Merck & Co. · DPP4 · 小分子

什么是 metformin + sitagliptin？

metformin + sitagliptin 是一种小分子，由Merck & Co.研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名Januvia ER, Janumet ER, Janumet XR
公司Merck & Co.
药物类别小分子
分子靶点DPP4
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Merck & Co.

作用机制

分子靶点

metformin + sitagliptin 作用于 1 个分子靶点：

DPP4dipeptidyl peptidase 4 (CD26, DPPIV)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

metformin + sitagliptin 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Metabolism and nutrition disordersType 2 diabetes mellitus✓ Approved

相关研究文献

PubMedTissue & cell2026-06-13

Intra-articular metformin and chlorogenic acid synergistically protect against cartilage degeneration by suppressing NF-κB/NLRP3 inflammasome axis in osteoarthritis.

Abdel-Kareem Mona A MA, Abd-Elrafea Nourhan N, Abdo Walied W, Atiba Ayman S AS et al.

Osteoarthritis (OA) is a leading cause of disability, driven by cartilage degradation, subchondral bone remodeling, and synovial inflammation. Activation of the NF-κB/NLRP3 inflammasome axis contributes to disease progression. This study investigated the chondroprotective and anti-inflammatory effects of intra-articular (IA) metformin (MET) and chlorogenic acid (CGA), alone or in combination, in a rabbit model of OA. OA was induced by monosodium iodoacetate (MIA) injection into the knee joints of male rabbits The rabbits were randomized into six groups: Control, MET + CGA, OA, OA + MET, OA + CGA, and OA + MET + CGA. Disease severity was evaluated via radiography, gross morphology, histopathology, and hematological and synovial fluid analyses. MIA induced OA manifested by joint space narrowing, osteophyte formation, and cartilage erosion, accompanied by elevated serum CRP, increased synovial IL-1β, IL-6, and TNF-α, and upregulation of NF-κB, NLRP3, caspase-1, GSDMD, IRF-1, and cartilage-degrading enzymes. MET or CGA alone significantly attenuated these changes, improving joint architecture, lowering inflammatory cytokines, and suppressing pyroptotic signaling. Combination therapy produced the most pronounced benefits, restoring near-normal cartilage structure, normalizing leukocyte profiles, and reducing molecular markers toward baseline. In silico findings revealed the affinity of CGA to bind with NLRP3 PYD, ASC PYD, IRF-1 and NF-κB p65. In conclusion, IA MET + CGA synergistically ameliorated structural and molecular hallmarks of OA via coordinated inhibition of NF-κB/NLRP3 inflammasome activation and pyroptosis. These findings highlight the translational potential of this dual therapy as a disease-modifying approach for OA management, pending further investigations.

PMID 42284731
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PubMedInternational journal of molecular sciences2026-06-12

Metformin Alleviates Stress-Induced Premature Senescence of Vascular Endothelial Cells by Regulating Mitocytosis.

Lu Hui H, Mu Qing Q, Wang Boqun B, Chen Yan Y et al.

Stress-induced premature senescence (SIPS) of endothelial cells can cause endothelial dysfunction. As a first-line antidiabetic agent, the specific role of metformin in SIPS has not yet been clarified. In this study, an in vitro SIPS model was induced by exposing human umbilical vein endothelial cells (HUVECs) to hydrogen peroxide (H2O2), and the effects of metformin on cell senescence, proliferation, migration, tube formation, and mitochondrial function were evaluated. Gene expressions altered by metformin were profiled via transcriptome sequencing. Specifically, the potential involvement of migrasome-mediated mitocytosis in metformin-driven effects was examined using confocal microscopy and siRNA-mediated silencing. The results showed that metformin significantly reduced SA-β-gal activity and restored the migration and tube-forming capacities of H2O2-induced senescent HUVECs. Moreover, metformin regulated mitochondrial dynamics, restored mitochondrial membrane potential, and attenuated intracellular oxidative stress. Notably, transcriptomic and functional analyses suggested that metformin enhanced migrasome formation and migrasome-mediated mitocytosis. Inhibition of migrasome formation by siTSPAN4 abolished the protective effect of metformin against SIPS. Collectively, these findings demonstrate that metformin alleviates early SIPS-associated changes in HUVECs and suggest that migrasome-mediated mitocytosis contributes to this protection by ameliorating mitochondrial dysfunction. This provides novel mechanistic insight into the vascular protective effects of metformin.

PMID 42278258
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PubMedApplied and environmental microbiology2026-06-12

Identification of a bacterial NCS1 family transporter enabling high-affinity uptake of the antidiabetic drug metformin.

Xu Zhi-Jing Z-J, Li Tao T, Zhou Ning-Yi N-Y

Metformin is a first-line antidiabetic medication for type 2 diabetes and a widely dispersed emerging pollutant in aquatic systems. During medication, its strong positive charge (pKa  =  12.4) under physiological conditions necessitates cellular uptake via non-specific cationic transporters, such as organic cation transporter 1 (OCT1) in humans. During bacterial biodegradation of metformin, it was also proposed that the transport of metformin into bacterial cells is a prerequisite. Despite progress in elucidating the biodegradation mechanism of metformin, the bacterial membrane transport systems involved remain largely unexplored. Here, we characterize a metformin transporter (MetT) from the metformin utilizer Aminobacter sp. strain NyZ550. Gene knockout and complementation experiments demonstrate that metT is essential for the growth of strain NyZ550 on metformin. Efficient bacterial degradation of metformin necessitates the presence of both the membrane transporter and the downstream catabolic enzyme. Phylogenetic analysis revealed that MetT is a member of the nucleobase cation symporter 1 (NCS1) family, but forms a separate clade distinct from previously characterized NCS1 members. It exhibits distinct polar localization within the cytoplasmic membrane, as evidenced by a MetT-green fluorescent protein fusion construct. Radiolabeled uptake assays using 14C-metformin revealed a substrate transport affinity (Km) of 15.90 ± 1.75 µM, which starkly contrasts with the millimolar-range Km of human OCT1. Structural modeling and site-directed mutagenesis revealed a substrate-binding cavity consisting of aromatic residues, likely facilitating substrate recognition through cation-π interactions. Overall, this study characterizes a functional bacterial metformin transporter and a new member from the emerging NCS1 transporter family.IMPORTANCEThe increasing global consumption of pharmaceuticals worldwide is contributing to the release of drugs and their catabolic byproducts into ecological systems through various routes, posing significant threats to environmental stability and public health. Environmental microbes can metabolize many of these molecules by evolving specific enzymes; however, efficient degradation necessitates their transport across the cell membrane, a process that remains poorly understood. In this study, we identified metformin transporter (MetT), a bacterial metformin transporter, from the metformin-utilizing strain NyZ550. MetT exhibits distinct specificity and transport affinity compared to human metformin transporters. This discovery offers new insights into the transport of metformin in prokaryotic cells and opens new avenues for exploring drug-microbe interactions and their implications for environmental biodegradation and gut biology.

PMID 42283632
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PubMedResearch square2026-06-12

Metformin Modulates Systemic Lipid Remodeling after Traumatic Brain Injury.

Gusdon Aaron M AM, Cho Sung-Min SM, Chen Hua H, Radmanesh Farid F et al.

Background Traumatic brain injury (TBI) induces systemic metabolic disturbances, particularly affecting lipid metabolism, which may contribute to secondary injury. Metformin has pleiotropic effects on mitochondrial function and lipid homeostasis, but its impact on the circulating lipidome after TBI remains poorly characterized. Methods We performed plasma lipidomic profiling in a porcine TBI model with metformin or control pretreatment. Paired pre- and post-TBI samples from 20 swine enabled within-subject comparisons. Lipidomic data were analyzed using complementary univariate and multivariate approaches, including paired differential abundance testing, principal component analysis (PCA), unsupervised hierarchical clustering with permutation-based cluster purity assessment, and sparse partial least squares discriminant analysis (sPLS-DA). Results Unsupervised analyses demonstrated coordinated lipidomic remodeling following TBI, characterized by enrichment of triglycerides and depletion of phosphatidylinositols. Metformin treatment had minimal effects on baseline metabolic profiles, with only subtle multivariate separation and near-chance classification performance. In contrast, post-TBI samples showed clearer treatment-associated differences, including improved separation in PCA, hierarchical clustering, and sPLS-DA models. These differences were driven by coordinated changes across multiple lipid classes rather than large shifts in individual metabolites. Notably, metformin treatment was associated with altered post-TBI patterns of triglycerides containing polyunsaturated fatty acids, phospholipids, lysophospholipids, and cholesteryl esters, suggesting modulation of injury-associated lipid remodeling. Conclusions Metformin exerts modest effects on baseline lipid metabolism but is associated with coordinated alterations in the systemic lipidomic response following TBI. These findings support a context-dependent role for metformin as a modulator of post-injury metabolic remodeling and highlight lipid pathways as potential targets for therapeutic intervention after TBI.

PMID 42281978
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PubMedGraefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie2026-06-12

Retinal and optic nerve measures after initiation of empagliflozin plus metformin versus metformin alone in early type 2 diabetes: a prospective observational comparative study.

Argon Bora Deniz BD, Çakır Akın A, Çakır Sezin Doğan SD, Safalı Fidan F et al.

To explore whether empagliflozin added to metformin is associated with short-term changes in optical coherence tomography (OCT) and visual evoked potential (VEP) parameters in adults with newly diagnosed early type 2 diabetes mellitus (T2DM). In this prospective observational comparative study, adults with newly diagnosed T2DM received metformin alone (M) or empagliflozin plus metformin (EM) according to routine clinical care. Outcomes were macular ganglion cell complex (GCC) and peripapillary retinal nerve fibre layer (RNFL) thickness measured by OCT, and pattern-reversal VEP parameters. Confounding by indication was addressed using propensity-score overlap weighting. Six-month change was analysed using baseline-adjusted overlap-weighted regression with HC3 robust standard errors. Secondary endpoints were controlled using the Benjamini-Hochberg false discovery rate. An additional exploratory repeated-measures mixed-effects analysis incorporating baseline, 3-month, and 6-month data was also performed. Only right eyes were included. Eighty participants were analysed (40 per group). Overlap weighting achieved excellent covariate balance (maximum weighted absolute standardized mean difference, 0.017). At 6 months, mean GCC change favoured EM over M (β = +3.33 μm; 95% CI, 2.90 to 3.76; p < 0.001). Secondary outcomes also favoured EM, including shorter VEP P100 latency (β = -10.06 ms; 95% CI, - 12.07 to - 8.05; q < 0.001) and greater VEP N75-P100 amplitude (β = +4.17 µV; 95% CI, 3.21 to 5.14; q < 0.001), with directionally consistent findings across RNFL and GCC sectoral measures. In this exploratory prospective observational study, empagliflozin added to metformin was associated with short-term OCT and VEP changes compatible with a potential neuroprotective signal in early T2DM. Findings require confirmation in longer-term randomised or robust quasi-experimental studies.

PMID 42283730
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PubMedbioRxiv : the preprint server for biology2026-06-12

Metformin Redirects Autophagy from Bulk Turnover to Mitochondrial Clearance.

Mutawi Thuraya M TM, Malvankar Shweta R SR, Graziani Andrea A, Shah Udita U et al.

Metformin is the most widely prescribed antidiabetic drug and an active candidate for repurposing in oncology. How it engages autophagy - a pathway central to both its metabolic and its anti-tumor effects - has remained unresolved, with reports of induction, suppression, and no effect. Here we show that metformin reroutes rather than induces or inhibits autophagy in human cancer cells: at therapeutic concentrations, it suppresses bulk cytosolic turnover by selectively blocking WIPI2-mediated phagophore tethering, while the ULK1 initiation complex relocates toward mitochondria and engages selective mitochondrial clearance. We trace this redirection to mitochondrial complex I inhibition, registered as a shift in the NAD + /NADH ratio before any change in the adenylate pool, and to a non-canonical reprogramming of the ULK1 complex that operates independently of mTORC1 and of the proposed PEN2-lysosomal route. AMPK is engaged in a subunit-specific manner that restrains ATG13 at initiation and enables WIPI2 displacement at maturation. The ULK1 complex is therefore the node at which metformin sets autophagic substrate selection, with direct implications for combination therapy in diabetes and cancer.

PMID 42282636
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