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glimepiride + metformin (HOE490 O / HOE4900 / Amaryl M IR)

✓ Approved

Sanofi S.A · KCNJ11 · Small Molecule

What is glimepiride + metformin?

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

Drug Profile

Brand NamesHOE490 O, HOE4900, Amaryl M IR
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 acts on 2 molecular targets:

KCNJ11potassium inwardly rectifying channel subfamily J member 11 (BIR, HHF2)
ABCC8ATP binding cassette subfamily C member 8 (MRP8, SUR1delta2)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

glimepiride + 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 journal of toxicology2026-09-20

Drug-drug Interaction Between Alpinetin and Glimepiride and its Potential Mechanism in Rats.

Qin Mengnan M, Zhao Wenwen W, Li Xin X

Given that alpinetin possesses hypoglycemic and cardioprotective properties, it holds potential for co-administration with the antidiabetic agent glimepiride. The aim was to evaluate the impact of alpinetin on the pharmacokinetics and hypoglycemic efficacy of glimepiride, thereby providing a foundation for the development of alpinetin and informing its potential clinical translation. Pharmacokinetic studies were performed in rats following oral administration of glimepiride (1 mg/kg) alone or combined with alpinetin (30 mg/kg). The effect of the combination of glimepiride and alpinetin on blood glucose levels was investigated in a rat model of type 2 diabetes mellitus (T2DM). In vitro experiments were conducted to evaluate the effect of alpinetin on glimepiride metabolic stability and to assess its role on cytochrome P450 2C9 (CYP2C9) activity. Co-administration of glimepiride with alpinetin resulted in significant changes in the pharmacokinetics of glimepiride, as evidenced by an increase in area under the concentration-time curve (AUC), elimination half-life (t1/2), maximum concentration (Cmax), and a decrease in clearance. Glimepiride in combination with alpinetin enhanced the hypoglycemic effect in T2DM rats. Mechanistic studies in liver microsomes revealed that alpinetin improved glimepiride metabolic stability and inhibited CYP2C9 activity. The combination of glimepiride with alpinetin may increase the systemic exposure of glimepiride through inhibition of CYP2C9 activity. This likely contributes to the enhanced hypoglycemic effect observed, but also underscores the need for caution regarding the potential risk of hypoglycemia.

PMID 42763797
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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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PubMedClinical ophthalmology (Auckland, N.Z.)2026-09-19

Longitudinal Changes in Corneal Epithelial and Central Corneal Thickness in Type 2 Diabetes Assessed by AS-OCT: A Real-World Study.

Boyacı İhsan İ, Demirci Göktuğ G

To evaluate longitudinal changes in central corneal epithelial thickness (CCET) and central corneal thickness (CCT) using anterior segment optical coherence tomography (AS-OCT) over 12 months in adults with type 2 diabetes receiving one of two routinely prescribed oral antidiabetic regimens, and to explore their association with glycemic changes. In this retrospective observational cohort study, 40 adults with type 2 diabetes receiving one of two routinely prescribed treatment regimens (vildagliptin-metformin, n=19; empagliflozin-metformin, n=21) underwent AS-OCT at baseline, 3 months, and 12 months. Glycated hemoglobin and fasting plasma glucose were assessed at each visit. Precision analysis indicated detectable between-group differences of 4.7 µm for CCT and 6.1 µm for CCET. Both groups showed significant within-group glycated hemoglobin improvement (mean reduction: -2.28% and -2.88% in the vildagliptin-metformin and empagliflozin-metformin groups, respectively; p<0.05) without between-group differences. CCT and CCET showed no statistically detectable longitudinal change over 12 months, with no significant differences in longitudinal change between groups. Glycated hemoglobin change showed a modest independent association with CCT change (β = 0.81 µm per 1% glycated hemoglobin; 95% CI 0.20-1.42; p=0.011; n=32). Corneal structural parameters showed no statistically detectable longitudinal change or between-group difference over 12 months. Given the modest sample size and observational design, these findings should be considered hypothesis-generating and require confirmation in larger prospective studies.

PMID 42761673
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PubMedFrontiers in pharmacology2026-09-19

Repurposed metformin-apigenin combination therapy for metabolic dysfunction-associated steatohepatitis: from integrative multi-omics discovery to in vivo validation.

Zhang Kanglong K, Chen Yihua Y, Ran Linwei L, Tong Weizhao W et al.

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease. Although recent drugs have been approved, the complex pathophysiology of MASH limits monotherapy efficacy and generates considerable inter-patient heterogeneity. The purpose of this research was to identify new molecular targets and develop a rational combination therapeutic approach for MASH. To determine the molecular signatures of MASH mouse models and healthy controls, we conducted bulk RNA sequencing on liver tissues and then analyzed the data with a variety of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, weighted gene co-expression network analysis, and so on. The role of lipidomic profiling was to determine the relation between genes and lipids. The human MASH liver specimens were used to test clinical relevance. Causal relationships were measured using Mendelian randomization (MR). Direct interaction between the drugs and the target was predicted by molecular docking and molecular dynamics simulations. The efficacy of metformin and apigenin as single therapy and in combination was assessed in vivo using MASH mice. We discovered a five-gene signature (Gpd2, Cybb, Clec12a, Ifi211, and Tifab), which was highly expressed by MASH and was strongly connected to lipid metabolism and inflammatory events. Integrative lipidomic correlation analysis showed that these genes were specifically linked with certain lipotoxic species. Molecular docking and molecular dynamics simulation studies have shown that metformin and apigenin, respectively, bind to Gpd2 and Cybb directly. Both agents alleviated the MASH pathology, and combined therapy was more effective than monotherapy. This study provides a new five-gene signature transcending hepatic lipid dysregulation and inflammation associated with MASH. The demonstration that metformin targets Gpd2 and apigenin targets Cybb provides a mechanistic basis for combination therapy, which exhibited superior efficacy over monotherapy. This repurposed oral drug combination offers a promising multi-target strategy for MASH treatment.

PMID 42761201
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PubMedFrontiers in endocrinology2026-09-19

Adverse event reporting signals for SGLT-2 inhibitor-metformin combination therapy: a disproportionality analysis of the FAERS database.

Zhou Wei W, Xia Yimiao Y, Li Jing J, Wang Facai F

This study aimed to evaluate the real-world safety profile of combination therapy with a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) and metformin relative to monotherapy, utilizing the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. We extracted adverse event (AE) reports from the FAERS database from the first quarter (Q1) of 2013 to the fourth quarter (Q4) of 2025 in which the combined regimen (ertugliflozin, dapagliflozin, empagliflozin, or canagliflozin plus metformin) was designated as the primary suspect. Disproportionality analyses were performed using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) algorithms. Additionally, we examined the time-to-onset distribution and the clinical outcomes of the documented AEs. A total of 23,407 combination-therapy reports were included. At the System Organ Class (SOC) level, ROR-based signal detection identified pronounced disproportionalities in metabolism and nutrition disorders (ROR = 9.00), renal and urinary disorders (ROR = 3.91), reproductive system and breast disorders (ROR = 2.59), and infections and infestations (ROR = 2.49). At the Preferred Term (PT) level, the five most frequently reported events cross-validated by all four algorithms were diabetic ketoacidosis (n = 3,522), weight decreased (n = 1,294), blood glucose increased (n = 1,226), acute kidney injury (n = 1,153), and euglycaemic diabetic ketoacidosis (euDKA, n = 1,114). Notably, euDKA demonstrated the highest signal intensity (ROR = 335.43), with the point estimate for the combination group being numerically higher than that observed for SGLT-2i monotherapy (ROR = 185.24). Regarding documented outcomes, hospitalisation or prolonged hospitalisation constituted the most prevalent serious outcome (33.7%), followed by life-threatening events (7.6%) and death (2.7%). In the sub-cohort with definitive time-to-onset data, 39.56% of AEs occurred within the first 30 days following treatment initiation. This pharmacovigilance analysis of the FAERS database detected significant disproportionality signals for SGLT-2i/metformin combination therapy, particularly within metabolic/nutritional, renal/urinary, and infectious disease categories. The euDKA signal appeared prominent in descriptive comparisons. The predominance of hospitalisation-related events, coupled with the substantial concentration of AEs within the initial 30-day window, highlights the early treatment phase as a potentially critical monitoring period. These exploratory findings warrant rigorous validation through prospective cohort studies.

PMID 42761174
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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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