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glimepiride + metformin SR (Amaryl Mex / Amaryl M SR)

✓ Approved

Sanofi S.A · KCNJ11 · Small Molecule

What is glimepiride + metformin SR?

glimepiride + metformin SR is a small molecule developed by Sanofi S.A. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesAmaryl Mex, Amaryl M SR
CompanySanofi S.A
Drug ClassSmall Molecule
Molecular TargetKCNJ11, ABCC8
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Sanofi S.A

Mechanism of Action

Molecular Targets

glimepiride + metformin SR acts on 2 molecular targets:

KCNJ11potassium inwardly rectifying channel subfamily J member 11 (BIR, HHF2)
ABCC8ATP binding cassette subfamily C member 8 (MRP8, SUR1delta2)
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Therapeutic Indications

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

Therapeutic AreaConditionPhase
Metabolism and nutrition disordersType 2 diabetes mellitus✓ Approved

Related Research Articles

PubMedJournal of ovarian research2026-09-19

Hypothalamic Epac2/AKT/GnRH signalling is associated with metformin-responsive neuroendocrine improvement in a PCOS model.

Guo Na N, Li Hongyun H, He Jinhong J, Zhou Huanhuan H et al.

Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder characterised by hypothalamic-pituitary-gonadal (HPG) axis dysfunction and pathological gonadotropin-releasing hormone (GnRH) hypersecretion. While metformin demonstrates therapeutic efficacy in PCOS, its potential neuroendocrine mechanisms remain incompletely understood. This study aimed to investigate the involvement of hypothalamic signalling in metformin-responsive neuroendocrine regulation in PCOS. Letrozole-induced PCOS rat models were treated with metformin to assess reproductive and metabolic outcomes. Data-independent acquisition (DIA) proteomics of hypothalamic tissue was performed to identify dysregulated pathways, followed by network analysis to explore candidate regulatory nodes. Mechanistic investigations were conducted in glucosamine-induced insulin-resistant GT1-7 GnRH neurons using pharmacological modulation and siRNA knockdown. In vivo functional relevance was examined using AAV-mediated Epac2 knockdown in the mouse arcuate nucleus. Metformin improved metabolic and reproductive abnormalities in PCOS rats, including insulin resistance, GnRH/LH hypersecretion, estrous cyclicity disruption, and ovarian morphological alterations. Hypothalamic proteomic and network analyses suggested that metformin-responsive changes were associated with insulin and cAMP-related signalling pathways. In GT1-7 neurons, metformin increased Epac2 expression, restored AKT signalling, and reduced GnRH overproduction under insulin-resistant conditions. Hypothalamic Epac2 knockdown reduced AKT signalling and was associated with systemic insulin resistance, increased GnRH/LH secretion, and preliminary supportive ovarian morphological observations, consistent with a functional contribution of Epac2 to reproductive-metabolic regulation. These findings support the involvement of hypothalamic Epac2/AKT/GnRH signalling in metformin-responsive neuroendocrine regulation in PCOS. Further studies are required to determine the relative contributions of central and peripheral mechanisms.

PMID 42760541
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PubMedCardiovascular research2026-09-19

Lysosomal signaling pathways influence heart rhythm, and regulate atrial function.

Akerman Emily E, Capel Rebecca A RA, Rog-Zielinska Eva A EA, Winbo Annika A et al.

In the heart, endogenous nicotinic acid adenine dinucleotide phosphate (NAADP) triggers lysosomal calcium (Ca2+) release to augment sarcoplasmic reticulum (SR) Ca2+ sequestration, producing larger Ca2+ transients. However, the role of lysosomal Ca2+ signals in pacemaker activity, a distinct Ca2+-operated function of the sinoatrial node (SAN), or in the atrial myocardium has not been investigated. Pharmacological or genetic ablation of the NAADP pathway inhibits the spontaneous beating rate response to β-adrenergic stimulation in intact SAN. We found intracellular signaling microdomains between lysosomes and neighboring SR or mitochondria in mouse, and goat tissue. The spatial relationship between lysosomes and other Ca2+-handling organelles are altered in goat atrial fibrillation. Furthermore, we demonstrate atrial myocytes produce 3'-5'-cyclic adenosine monophosphate (cAMP) in response to lysosomal signaling, adding a novel trigger for cyclic nucleotide signaling. Our findings support the hypothesis that lysosomal Ca2+ signaling contributes to regulation of cardiomyocyte cAMP levels and pacemaker activity.

PMID 42760609
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PubMedFrontiers in plant science2026-09-19

Drip fertigation technique with planting models strategies trigger grain filling, endogenous hormonal changes and maize productivity under semi-arid regions.

Wang Jiaqi J, Diao Jian J, Xu Zhe Z, Ma Ning N et al.

Mulch drip fertigation strategies have been widely adopted to improve maize productivity in semi-arid regions. However, the impact of the mulch-based drip fertigation on endogenous hormone dynamics in crops and grain yield has not been fully elucidated, and the biochemical mechanisms underlying yield improvement under different drip fertigation strategies remain unclear. Grain filling has a significant impact on maize production. The aim of this study was to explore the effect of plastic film mulching materials on maize grain filling under a drip fertigation strategy, and the relationship between this effect and changes in endogenous hormones. This study compared biodegradable film mulching (BM) with soil crust ridges (SR) under high (H), medium (M), and low (L) drip irrigation conditions, and measured that the grain filling characteristics and changes in grain endogenous hormones in various parts of maize ears during the growth stage. The results showed that the grain filling rate, dry matter plant-1, hormone changes, yield components, water use efficiency (WUE), and ET of maize under the BMH treatment were significantly higher than those under the SR treatment. BMH treatment significantly increased soil water storage significantly increased plant hormone contents such as abscisic acid (ABA), indole-3-Acetic acid (IAA), and zeatin + Zeatin Riboside (Z+ZR), and decreased the evolution rate of gibberellins (Gas) and ethylene, thereby increasing maize yield. These results indicate that BMH treatment improved the filling process, soil respiration rate, WUE, yield, and yield composition of maize. High drip fertigation with BM or SR treatment significantly affected endogenous hormone changes, thereby regulating the activity grain-filling period (AGP), maximum grain-filling rate (Gmax), maximum grain weight (Wmax), mean grain-filling rates (Gmean) and occurrence time of maximal filling rate (Tmax) of maize. In addition, high drip fertigation and the BM strategy significantly increased soil water storage and soil respiration rate during the grain filling period. Based on these results, we conclude that BMH significantly improved soil water storage, thereby regulating the maize grain filling rate, which was significantly correlated with the balance of endogenous hormones in the grains.

PMID 42760979
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PubMedBritish dental journal2026-09-19

Rethinking systemic adjuncts in periodontitis: a single centre acquisition cost comparison of antimicrobial and non-antimicrobial therapies.

Almanie Lina L, Neves Vitor C M VCM

Aims To compare National Health Service (NHS) acquisition costs of systemic antimicrobial regimens with emerging non-antimicrobial adjuncts in periodontal therapy and to model potential national financial implications.Methods A secondary acquisition cost comparison analysis was undertaken using three-year prescription data (2021-2024) from a service evaluation at Charles Clifford Dental Hospital. Antibiotic prescriptions were cross-referenced with clinical records to identify those issued for periodontitis. Direct acquisition costs were calculated using Sheffield Teaching Hospitals NHS Foundation Trust pricing.Results Of 643 antibiotic prescriptions, 445 (69.2%) were issued for periodontitis. Azithromycin accounted for 93.5% of periodontal prescriptions, whereas guideline-recommended amoxicillin plus metronidazole (A+M) represented 1.6%. Compared with A+M (£2.81 per course), azithromycin reduced acquisition costs by 55.16%. Non-antimicrobial adjuncts demonstrated substantially greater reductions depending on treatment duration, with metformin 500 mg achieving up to 91.46% reduction.Conclusions Non-antimicrobial systemic adjuncts demonstrate considerable direct cost advantages over traditional antimicrobial regimens. These findings highlight potential economic and antimicrobial stewardship benefits and support the need for formal cost-effectiveness analyses to inform future prescribing guidance.

PMID 42760348
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PubMedCell biochemistry and biophysics2026-09-19

Acetone Extract of Annona Muricata Linn Leaf Counteracts Hyperglycemia-Associated Metabolic Dysregulation by Modulating Oxidative Stress and Hepatic Carbohydrate Metabolism in Streptozotocin-Induced Diabetic Rats.

Omiyale Benjamin Olusola BO, Ekundayo Bidemi Emmanuel BE, Olusola Olutosin Samuel OS, Idowu Olajumoke Tolulope OT et al.

Annona muricata is widely recognized for its rich phenolic composition and potent antioxidant activity, suggesting therapeutic potential in diabetes management. This study investigated the mechanistic antidiabetic effects of acetone extract of A. muricata leaf on hepatic carbohydrate metabolism, oxidative stress, and hepatic function in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in forty-two male Wistar rats by intraperitoneal injection of STZ (55 mg/kg). Diabetic animals (n = 7 per group) were treated with 25, 50, and 100 mg/kg of the extract (yield: 10.08% w/w) for 28 days, while metformin (200 mg/kg) served as the standard drug. Hepatic antioxidant enzyme activities, lipid peroxidation, serum albumin, lactate dehydrogenase (LDH), and histopathological alterations were evaluated to assess oxidative status and hepatic function, alongside the activities of key carbohydrate-metabolizing enzymes and mRNA expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) and glucose transporter 4 (GLUT4). Administration of the acetone extract significantly enhanced hepatic antioxidant defenses, as demonstrated by increased levels of glutathione and increased activities of antioxidant enzymes, accompanied by a marked reduction in lipid peroxidation. Additionally, the extract significantly restored serum albumin levels and reduced LDH activity, indicating improved hepatocellular integrity. Furthermore, the extract significantly impacted the activities of carbohydrate-metabolizing enzymes and restored the expression of PPAR-γ and GLUT4 toward physiological levels. These results suggest that the antidiabetic activity of A. muricata may be mediated by the attenuation of oxidative stress, preservation of hepatic function, and regulation of hepatic carbohydrate metabolism and glucose transporter signalling pathways, highlighting its potential as a promising phytotherapeutic agent for the management of diabetes.

PMID 42760481
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PubMedFrontiers in nutrition2026-09-19

Nobiletin ameliorates diabetic nephropathy by modulating TP53-associated PANoptosis: an experimental study.

Zhang Biwei B, Liu Yi Y, Ma Leilei L, Zhao Yingjie Y et al.

Nobiletin (NOB), a naturally occurring polymethoxyflavone enriched in Citri Reticulatae Pericarpium-the dried peel of mature citrus fruit-has attracted increasing attention because of its multi-target pharmacological activities. This study explored the protective effects of NOB on diabetic nephropathy (DN), with a focus on TP53-associated PANoptosis and TFEB-related lysosomal and energy metabolic changes. Forty male db/db mice were randomly assigned to the model, metformin, low-dose NOB (30 mg/kg/day), and high-dose NOB (60 mg/kg/day) groups, with 10 mice per group. Ten age-matched male db/m mice served as non-diabetic controls. Treatments were administered by gavage for 8 weeks. Metabolic parameters, lipid profiles, inflammatory cytokines, renal function, histopathology, untargeted metabolomics, energy metabolites, network pharmacology, surface plasmon resonance (SPR), immunofluorescence, qPCR, and Western blot analyses were performed. Supplementary in vitro validation was performed in high-glucose-treated HK2 renal tubular epithelial cells with TP53 knockdown or overexpression. NOB treatment reduced FBG, OGTT-AUC, INS, HOMA-IR, GSP, TC, TG, and LDL-C while increasing HDL-C. High-dose NOB improved renal function, reduced IL-1β and IL-6, and alleviated histological damage. Untargeted metabolomics suggested that NOB partially restored pathway-level changes related to oxidative phosphorylation, lysosomal function, fatty acid metabolism, and energy metabolism. Network pharmacology identified TP53 as a central candidate target, and SPR analysis suggested binding between NOB and TP53 protein. NOB treatment reduced TP53 signal, promoted TFEB nuclear localization, and suppressed pyroptosis-, apoptosis-, and necroptosis-related markers in diabetic kidneys. Representative HK2 Western blot experiments showed expression patterns consistent with attenuation of high-glucose-induced PANoptosis-related protein activation after TP53 knockdown and partial counteraction of the NOB-associated regulatory pattern after TP53 overexpression. NOB ameliorated DN-related metabolic disturbance, inflammation, renal dysfunction, histological injury, and fibrosis. These protective effects were associated with reduced TP53 activation, restoration of TFEB-related lysosomal and energy metabolic status, and suppression of PANoptosis-related pathways. Supplementary HK2 cell experiments provided supportive, representative evidence for the involvement of TP53 in high-glucose-induced PANoptosis-related protein activation and in the regulatory effect of NOB. These findings suggest that NOB may be a promising natural compound for DN intervention.

PMID 42761023
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