The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifact...The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.展开更多
Metformin is generally safe but can cause lactic acidosis and rarely organ dysfunction during overdose.Misuse for weight loss,especially in undiagnosed eating disorder,is concerning.In stigmatized settings such condit...Metformin is generally safe but can cause lactic acidosis and rarely organ dysfunction during overdose.Misuse for weight loss,especially in undiagnosed eating disorder,is concerning.In stigmatized settings such conditions may go unrecognized This case illustrated severe complications from chronic metformin abuse in a young female with suspected anorexia nervosa,highlighting the need for integrated medical and psychiatric care.To the best of our knowledge,this is only the second case report of multiple organ dysfunction syndrome(MODS)due to metformin toxicity.CASE SUMMARY Here,we reported a rare case of MODS involving four organs due to metformin abuse.A 22-year-old female located in Syria with a history suspicious of anorexia nervosa presented with dehydration,diarrhea,and altered consciousness.Labs revealed mixed high and normal anion gap metabolic acidosis from starvation ketosis and bicarbonate loss.She recovered with supportive care but returned 3 months later in shock with severe acidemia,kidney injury,pancreatitis,and liver dysfunction,consistent with MODS.Further history revealed chronic metformin abuse(up to 3000 mg/day)for weight loss.She recovered fully and began cognitive behavioral therapy.This case underscored the dangers of metformin misuse in eating disorders.CONCLUSION This case highlighted the potentially life-threatening consequences of surreptitious metformin abuse in the context of an underlying eating disorder.Early recognition,thorough history-taking,and multidisciplinary management,including psychiatric support,are essential for recovery and prevention of recurrence.展开更多
Diabetes mellitus,particularly type 2 diabetes mellitus(T2DM),poses a significant global health challenge.Traditional management strategies primarily focus on glycemic control;however,there is a growing need for compr...Diabetes mellitus,particularly type 2 diabetes mellitus(T2DM),poses a significant global health challenge.Traditional management strategies primarily focus on glycemic control;however,there is a growing need for comprehensive approaches addressing the complex pathophysiology of diabetes complications.The recent study by Attia et al explores the potential of a novel therapy combining metformin with cholecalciferol(vitamin D3)and taurine to mitigate T2DM-related complications in a rat model.The findings indicate that this treatment combination improves glycemic control and reduces oxidative stress,inflammation,and lipid abnormalities.However,the study is limited by a lack of safety profile data and in-depth molecular mechanism insights.This editorial critically highlights the study's strengths and weaknesses,compares it against other combination therapy research in T2DM,and underscores the need to explore further the mechanisms underpinning the observed therapeutic effects and investigate the safety profile of this novel approach.展开更多
The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tum...The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tumors.However,its underlying mechanisms remain elusive.In this work,we explore the role of receptor-interacting protein 1(RIP1)which plays a crucial role in the process of cell death,in metformin-induced anticancer activities in lung cancer.Metformin inhibits lung cancer cell proliferation in a dose-dependent manner and promotes apoptotic cell death,as evidenced by metformin-induced PARP and caspase cleavage.Furthermore,the pan-caspase inhibitor z-VAD-fmk reverses metformin-induced cell death.Western blot and qPCR results suggest that metformin markedly downregulates RIP1 expression without affecting its mRNA and ubiquitination levels(0 vs 80 mmol/L,100%vs 20%,100%vs 15%).Additionally,co-immunoprecipitation and immunofluorescence results reveal that metformin may suppress RIP1 expression in an Hsp70-dependent manner,as metformin promotes Hsp70 degradation,and Hsp70 endogenously interacts with RIP1.Subsequent CCK-8,flow cytometry,and Western blot analyses suggest that metformin decreases Hsp70/RIP1 expression through AMPK/PKA/GSK-3βaxis.Consistently,results from a subcutaneous transplant tumor model indicate that metformin retards tumor growth without affecting mouse body weight.Collectively,these data highlight the part of RIP1 in metformin-induced anticancer activities in lung cancer in vitro and in vivo,providing novel strategy for lung cancer administration.展开更多
Renal tubular injury has emerged as a critical factor in the progression of diabetic kidney disease(DKD).Given renal tubules'high mitochondrial density and susceptibility to mitochondrial dysregulation and ferropt...Renal tubular injury has emerged as a critical factor in the progression of diabetic kidney disease(DKD).Given renal tubules'high mitochondrial density and susceptibility to mitochondrial dysregulation and ferroptosis,targeting these pathways could offer therapeutic potential.Metformin(MET),a first-line therapy for type 2 diabetes mellitus(T2DM),exerts reno-protective effects by improving mitochon-drial function and attenuating fibrosis;however,its role in regulating ferroptosis in DKD remains unclear.This study aimed to investigate the role of MET in modulating mitophagy and ferroptosis in diabetic kidneys.In diabetic mouse models,MET notably alleviated tubular injury by promoting mitophagy and reducing ferroptosis,as shown by increasing levels of phosphatase and tensin homolog(PTEN)-induced putative kinase 1(PINK1)and Parkin,while decreased levels of malondialdehyde(MDA)and iron con-tent.Mechanistically,MET downregulated the hypoxia-inducible factor-1alpha(HIF-1α)/myo-inositol oxygenase(MIOX)signaling axis in renal tubular epithelial cells(RTECs),thereby restoring mitophagy and inhibiting ferroptosis.These findings demonstrate that MET mitigates diabetic renal injury by promoting mitophagy and countering ferroptosis via suppressing the HIF-1α/MIOX pathway,high-lighting its potential as a therapeutic intervention for halting DKD progression.展开更多
Background:Diabetes,a metabolic disease marked by endocrine dysfunctions,significantly impacts oxidative stress pathways.This study explores the protective effects of lemongrass extract(LE),citral,and lemongrass extra...Background:Diabetes,a metabolic disease marked by endocrine dysfunctions,significantly impacts oxidative stress pathways.This study explores the protective effects of lemongrass extract(LE),citral,and lemongrass extract-synthesized silver nanoparticles(LE-AgNP)against hyperglycemia-induced oxidative stress by modulating the Nrf2 pathway,which is crucial for antioxidant responses.Methods:Various techniques characterized the nanoparticles,including ultraviolet–visible spectroscopy,dynamic light scattering,zeta potential analysis,Fouriertransform infrared spectroscopy,scanning electron microscopy and transmission electron microscopy.Seventy rats,divided into seven groups,were used for in vivo experiments.Type 2 diabetes was induced using streptozotocin(65 mg/kg)and nicotinamide(90 mg/kg).After six weeks,biochemical parameters such as total antioxidant capacity,malondialdehyde,Nrf2,and Nrf2 miRNA were evaluated in pancreas tissue and blood serum,along with serum blood glucose levels.Results:LE-AgNP significantly improved weight gain,reduced food and water intake,and lowered blood glucose levels in diabetic rats.LE and citral did not significantly alter these parameters but prevented the decline in Nrf2 gene expression.LE-AgNP showed a significant increase in Nrf2 gene expression compared to the diabetic control group.Conclusions:This study highlights the potential of LE,citral,and especially LE-AgNP in mitigating oxidative stress induced by diabetes.LE-AgNP demonstrated superior therapeutic benefits,including improved oxidative stress conditions and hypoglycemic effects.展开更多
Background:Polycystic ovary syndrome(PCOS)is one of the most common reproductive endocrine metabolic diseases.Combined use of metformin and diane-35 has better curative effect in regulating serum hormone level(LH,FSH,...Background:Polycystic ovary syndrome(PCOS)is one of the most common reproductive endocrine metabolic diseases.Combined use of metformin and diane-35 has better curative effect in regulating serum hormone level(LH,FSH,T and E2)than using metformin alone.Traditional Chinese medicine(TCM)can also be used to treat PCOS.According to some studies,the combined use of metformin and diane-35 and TCM have achieved better curative effect than combining metformin and diane-35 in the treatment of patients with PCOS.Methods:Computerized searches of the science,Medline,VIP,Wan Fang and China HowNet(CNKI)databases were conducted to identify eligible randomized controlled trials(RCTs)from the data obtained up to March 1,2022.The Cochrane Collaboration risk of bias tool was used to assess the risk of bias in individual RCTs,and R software(version 4.0.3)was used for data statistical analysis.Results:Nine RCTs involving 1035 patients were included.Comparing to D+M,significant reduce of LH(mean difference[MD]:-1.93,95%confidence interval[CI]:-3.44,-0.42;Unit:U/L P<0.01;I2=89%)、T(MD:-1.44,95%CI-2.59,-0.30;Unit:nmol/L P<0.01;I2=98%)and significant increase of E2(MD:31.43,95%CI 24.54,38.33;Unit:pmol/L P<0.01;I2=96%)were shown in TCM+D+M.Comparing to D+M,TCM+D+M group has higher ovulation rate(RR 1.1495%CI 1.07,1.22;P=0.42;I2=0%)and higher pregnancy rate(RR 1.2995%CI 1.15,1.44;P=0.37;I2=7%).There is no significant difference between the two therapies in FSH changes(MD:-1.00,95%CI-2.27,0.28;Unit:U/L P<0.01;I2=95%).Subgroup analysis showed that compared with the Guizhi Fuling capsule group,the Kuntai capsule group had more FSH reduction and E2 increase more.In other outcome indicators,the two subgroup did not show significant differences.Conclusion:Kuntai Capsule+Diane-35+Metformin is better than Guizhi Fuling Capsule in reducing FSH,and it is also better in increasing E2.There was no significant difference between the two in LH and T hormones.There was no significant difference between Kuntai Capsules+Diane-35+Metformin and Guizhi Fuling Capsules+Diane-35+Metformin.As for the effect in lessen insulin resistance,Kuntai Capsule+Diane-35+Metformin was significantly better than Guizhi Fuling Capsules+Diane-35+Metformin.展开更多
Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications.The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism,...Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications.The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism,thus contributing to the development of vascular disorders,especially atherosclerotic diseases.Aggressive glycemic control combined with vascular intervention is critical to the prevention and treatment of diabetes-associated atherosclerosis.It is suggested that metformin should be combined with hypoglycemic agents with proven vascular benefits for treating type 2 diabetes(T2DM)complicated with atherosclerotic diseases.Clinical studies indicates that the preferred combination is metformin with either glucagon-like peptide-1 receptor agonist or sodium/glucose cotransporter-2 inhibitor,which could offer additional vascular benefits and reduce the risk of atherosclerotic complications.Likewise,combination therapy with metformin and hypolipidemic agents has also shown additive effects on glucose control and lipid-lowering in patients with both diabetes and dyslipidemia,whereas extensive clinical trials using atherosclerotic-associated outcomes are required to support the vascular benefits.Moreover,co-administration of metformin with systemic antioxidant or anti-inflammatory therapy may also provide additional vascular benefits as indicated by several animal studies.For instance,a recent study found that additional supplementation of cholecalciferol and taurine enhanced metformin efficacy in controlling diabetes while reducing the risk of associated atherosclerotic complications.However,these potential benefits remain need validation by the evidence from clinical studies.Despite the limitations,such as heterogeneity across different patient populations,and deficiency in long-term outcomes,such efforts can contribute to finding optimal drug combinations to improve the management of T2DM and reduce its atherosclerotic complications.展开更多
In recent years,the incidence of type 2 diabetes mellitus(T2DM)caused by obesity in China has been increasing continuously,which has become a risk factor for the onset of T2DM and seriously affects the quality of life...In recent years,the incidence of type 2 diabetes mellitus(T2DM)caused by obesity in China has been increasing continuously,which has become a risk factor for the onset of T2DM and seriously affects the quality of life of patients.The conventional treatment methods include weight loss and regulating the body’s metabolism.Semaglutide,as a glucagon-like peptide-1 receptor agonist(GLP-1RA),mainly reduces patients’appetite,decreases their craving for high-fat and high-sugar foods,regulates hypothalamic feeding behavior,inhibits gastric emptying and gastrointestinal motility,and ultimately leads to weight loss.Metformin mainly acts on extra-islet tissues,increasing glucose utilization,reducing glucose production,and ultimately lowering blood glucose levels.Based on this,this article reviews relevant literature on authoritative websites such as CNKI and Wanfang,organizes the data,and analyzes the research progress of semaglutide combined with metformin in the treatment of obese T2DM.The aim is to bring more treatment options for obese T2DM and promote better prognosis for patients.展开更多
Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and th...Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and therapeutic strategies remain unattainable.Recent studies have recognized the involvement of microRNA-155(miR-155)in the pathogenesis of OA and most of its risk factors while also identifying the antidiabetic drug metformin as a potential modulator of disease progression.MiR-155,a key endogenous regulator of the immune system,mechano-transduction,and multiple genetic pathways,interacts with OA targets of cellular energetic and circadian homeostasis,promoting systemic and local articular inflammation,cartilage matrix degradation,and chondrocyte apoptosis.Metformin,widely used for type 2 diabetes,has demonstrated anti-inflammatory,anti-oxidative,and chondroprotective properties in OA,mainly through its activation of adenosine monophosphate-activated protein kinase and inhibition of nuclear factor kappa-B signalling.Enthrallingly,metformin targets the same cellular pathways as miR-155 with emerging evidence also suggesting miR-155 expression modulation,indicating synergistic,potentially disease-modifying effects in OA.This review highlights the central role of miR-155 in OA pathophysiology and its potential as a biomarker for disease diagnosis and progression.MiR-155 targeting-through microRNA therapeutics(mimics/antagomiRs)and/or metformin-could pave the way for innovative treatments,including novel articular delivery systems and cell-based therapies.展开更多
Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficienc...Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficiency and the onset,progression,and worsening of diabetic neuropathy(DNP)as well as its im-provement with supplementation in cases of deficiency.Major clinical guidelines for diabetes and DNP remain vague in their recommendations for B12 measu-rement and supplementation,and some guidelines do not address it at all.Given that vitamin B12 therapy is an economical,safe,and widely available treatment in most countries and supported by emerging evidence of its potential benefits,greater efforts should be made to promote systematic screening for vitamin B12 deficiency in all patients with DNP before establishing a definitive diagnosis as well as in patients with diabetes with risk factors for deficiency.Vitamin B12 deficiency should be treated in all affected patients,and supplementation should be considered in those with borderline levels when confirmatory diagnostic tests for deficiency are unavailable.Clinical guidelines should place greater emphasis on the recommendations for measuring and supplementing vitamin B12 in these patients.展开更多
Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given th...Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given the moderate efficacy of the dengue vaccine,[2]there is an urgent necessity to design host-directed therapeutic strategies,such as the repurposing of FDA-approved drugs,to combat dengue virus infection.展开更多
In previous studies, compound mefformin/glipizide was developed. Aim To discover the mechanism of drug release from factors influencing drug release from dosage form （the semi-permeable cry orifice） were investigate...In previous studies, compound mefformin/glipizide was developed. Aim To discover the mechanism of drug release from factors influencing drug release from dosage form （the semi-permeable cry orifice） were investigated. Results The influx of water that elementary osmotic pump tablet it. Methods Three rate-limiting membrane, tablet core and delivpassed the osmotic pump tablet was almost equal to the metformin release rate, while it was greatly less than the drug dissolution rate from tablet core. The size of orifice from 0. 4 mm to 0.8 mm had no influence on drug release. The osmotic pressure of tablet core was mainly caused by mefformin. Conclusion From the developed model of osmotic pump systems, it can be seen that only the water influx through the membrane is a rate-limiting step, not tablet core dissolution rate and solution influx, and only when the core dissolution rate is equal to the solution influx, the zero order release is seen in the osmotic pump systems.展开更多
Aim In this study, compound metformin/glipizide bilayer extended release tablets were formulated with hydroxypropyl methylcellulose （HPMC） by wet granulation technique in order to tackle the problems associated with...Aim In this study, compound metformin/glipizide bilayer extended release tablets were formulated with hydroxypropyl methylcellulose （HPMC） by wet granulation technique in order to tackle the problems associated with the muhidrug therapy of non-insulin dependent diabetes mellitus. Me^ls High-dose metformin is difficult to formulate into a tablet dosage form due to its poor compressibility and compactibility. In this study, the way to overcome the difficulty was to utilize stearic alcohol to prepare the tablet formulation. The influences of viscosity, amount of HPMC, and weight of fillers were investigated. The optimal formulation had acceptable physicochemical properties and released metformin and glipizide over 10 h. Results The data of metformin obtained from in vitro release fitted Higuchi kinetics best, while the release of glipizide in vitro was found to follow zero kinetics. Conclusion Compound metformin/glipizide bilayer extended release tablets have been successfully developed.展开更多
Aim To prepare the prolonged-released microspheres of mefformin hydrochloride. Methods Ion-exchange resin-drug mefformin hydrochloride complexes were prepared as core materials, and followed by coating using ethylcell...Aim To prepare the prolonged-released microspheres of mefformin hydrochloride. Methods Ion-exchange resin-drug mefformin hydrochloride complexes were prepared as core materials, and followed by coating using ethylcellulose （EC） by the emulsion solvent diffusion technique. The release rate of mefformin from the microcapsules was highly dependent on the encapsulating formulation, thus being used as an index for formulation screening. Orthogonal experiments were performed to optimize the coating formulation. Results The final chosen formulation for coating of mefformin microcapsules were as follows： （ 1 ） the ratio of EC （20cps） to EC （45cps） was 50：50; （2） the ratio of plasticizer to coating materials was 20% ;and （3） the ratio of resin-mefformin complexes to coating materials was 5 ： 1. Conclusion The prolonged release microspheres of mefformin hydrochloride were successfully prepared.展开更多
To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely us...To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely used oral insulinsensitizing agent,being prescribed to more than 100 million people worldwide,including patients with prediabetes,insulin resistance,and polycystic ovary syndrome.However,over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency.Of note,evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status.Vitamin B12(also referred to as cobalamin)is a water-soluble vitamin that is mainly obtained from animal-sourced foods.At the cellular level,vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection.Thus,vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities(e.g.,megaloblastic anemia and formation of hypersegmented neutrophils),progressive axonal demyelination and peripheral neuropathy.Nevertheless,no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy,and vitamin B12 deficiency remains frequently unrecognized in such individuals.Therefore,in this“field of vision”article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients,which could serve as a practical guide for identifying individuals at high risk for this condition.Moreover,we discuss additional relevant topics related to this field,including:(1)The lack of consensus about the exact definition of vitamin B12 deficiency;(2)The definition of reliable biomarkers of vitamin B12 status;(3)Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis;and(4)Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency.Finally,we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency,particularly when this condition is induced by metformin.展开更多
Drug transporters determine plasma and tissue exposure of a broad variety of drugs and play a critical role in drug-drug interaction （DDI）. In the present study, we aimed to investigate the effects of carvedilol on ...Drug transporters determine plasma and tissue exposure of a broad variety of drugs and play a critical role in drug-drug interaction （DDI）. In the present study, we aimed to investigate the effects of carvedilol on pharmacokinetics of metformin as well as the mechanism of their interaction. Results showed that plasma concentration of metformin was not significantly altered after single or 7-day co-administration of carvedilol, and the urinary excretion of metformin was also not influenced by carvedilol. However, the concentration of metformJn in the liver and kidney was markedly elevated. Similarly, carvedilol did not affect the renal elimination of metformin, but increased renal concentration in isolated kidney perfusion. On the other hand, carvedilol treatment did not affect the expressions of rOCTs and rMATE 1 in the liver and kidney of rats. After long-term co-administration, there were no differences in lactic acid （LCA）, uric acid （URIC） and creatinine （CREA） levels between two groups. These results indicated that carvedilol increased hepatic and renal distribution of metformin, resulting in local drug interaction.展开更多
BACKGROUND Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes.Due to the lack of randomized control trials,most of the data pertaining to the clinical course,ther...BACKGROUND Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes.Due to the lack of randomized control trials,most of the data pertaining to the clinical course,therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series.AIM To analyse the symptomology,clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.METHODS We performed a systematic search from PubMed,Science Direct,Reference Citation Analysis(https://www.referencecitationanalysis.com/)and Google Scholar databases using the terms“metformin”AND“toxicity”OR“overdose”OR“lactic acidosis”OR“hyperlactatemia”.The inclusion criteria were:(1)Case reports or case series with individual patient details;and(2)Reported toxicity or overdose of metformin in adults,published in the English language.Data regarding baseline demographics,clinical presentation,therapeutic interventions,intensive care unit course and overall outcome were collected.RESULTS Two hundred forty-two individual cases were analysed,from 158 case reports and 26 case series,with a cumulative mortality of 19.8%.214(88.4%)patients were diabetics on metformin.57(23.6%)had acute ingestion,but a great majority(76.4%)were on metformin in therapeutic doses when they developed toxicity.Metformin associated lactic acidosis(MALA)was the most commonly reported adverse effect present in 224(92.6%)patients.Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia.The organ support used was renal replacement therapy(RRT)(68.6%),vasopressors(58.7%)and invasive mechanical ventilation(52.9%).A majority of patients(68.6%)received RRT for toxin removal,renal dysfunction and correction of MALA.Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT.CONCLUSION Most of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions.These patients may develop severe lactic acidosis,leading to significant morbidity and need for organ support.Despite severe MALA and the need for multiple organ support,they may have good outcomes,especially when RRT is used.The dose of metformin,serum pH,lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.展开更多
An efficient and sensitive ion-pair HPLC-UV method using atenolol as internal standard （IS） was developed and validated for the determination of metformin in the plasma of diabetic rats. Plasma samples were deprotei...An efficient and sensitive ion-pair HPLC-UV method using atenolol as internal standard （IS） was developed and validated for the determination of metformin in the plasma of diabetic rats. Plasma samples were deproteinated with 10% （v/v） perchloric acid. Separation was achieved on a UltimateTM AQ-C18 column （250 mm×4.6 mm, 5 μm） with a mobile phase （pH 5.05） composed of acetonitrile-water （31：69, v/v, containing 0.002 M sodium dodecyl sulfate, 0.0125 M potassium dihydrogen phosphate, 0.015 M triethylamine） at a flow rate of 1.0 mL/min. The calibration curve was linear （r〉0.994） between 7.5 and 4000 ng/mL. The lower limit of quantification （LLOQ） was 7.5 ng/mL. The precision was validated and the relative standard deviation was in the range of 1.87% to 15.70%; the accuracy was between 93.98%-106.89%. The mean recoveries were 95.40% and 95.31% for metformin and IS, respectively. The relative error （RE） of stability at different storage conditions was within ±9.00%. This method was used to determine the concentration-time profile of metformin in diabetic rat plasma following an oral administration of metformin at the dose of 10 mg/kg. Our results indicated that ion-pair HPLC-UV method using UltimateTM AQ-C18 column was effective for the pharmacokinetic studies of high polarity compounds like metformin.展开更多
文摘The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.
文摘Metformin is generally safe but can cause lactic acidosis and rarely organ dysfunction during overdose.Misuse for weight loss,especially in undiagnosed eating disorder,is concerning.In stigmatized settings such conditions may go unrecognized This case illustrated severe complications from chronic metformin abuse in a young female with suspected anorexia nervosa,highlighting the need for integrated medical and psychiatric care.To the best of our knowledge,this is only the second case report of multiple organ dysfunction syndrome(MODS)due to metformin toxicity.CASE SUMMARY Here,we reported a rare case of MODS involving four organs due to metformin abuse.A 22-year-old female located in Syria with a history suspicious of anorexia nervosa presented with dehydration,diarrhea,and altered consciousness.Labs revealed mixed high and normal anion gap metabolic acidosis from starvation ketosis and bicarbonate loss.She recovered with supportive care but returned 3 months later in shock with severe acidemia,kidney injury,pancreatitis,and liver dysfunction,consistent with MODS.Further history revealed chronic metformin abuse(up to 3000 mg/day)for weight loss.She recovered fully and began cognitive behavioral therapy.This case underscored the dangers of metformin misuse in eating disorders.CONCLUSION This case highlighted the potentially life-threatening consequences of surreptitious metformin abuse in the context of an underlying eating disorder.Early recognition,thorough history-taking,and multidisciplinary management,including psychiatric support,are essential for recovery and prevention of recurrence.
文摘Diabetes mellitus,particularly type 2 diabetes mellitus(T2DM),poses a significant global health challenge.Traditional management strategies primarily focus on glycemic control;however,there is a growing need for comprehensive approaches addressing the complex pathophysiology of diabetes complications.The recent study by Attia et al explores the potential of a novel therapy combining metformin with cholecalciferol(vitamin D3)and taurine to mitigate T2DM-related complications in a rat model.The findings indicate that this treatment combination improves glycemic control and reduces oxidative stress,inflammation,and lipid abnormalities.However,the study is limited by a lack of safety profile data and in-depth molecular mechanism insights.This editorial critically highlights the study's strengths and weaknesses,compares it against other combination therapy research in T2DM,and underscores the need to explore further the mechanisms underpinning the observed therapeutic effects and investigate the safety profile of this novel approach.
文摘The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tumors.However,its underlying mechanisms remain elusive.In this work,we explore the role of receptor-interacting protein 1(RIP1)which plays a crucial role in the process of cell death,in metformin-induced anticancer activities in lung cancer.Metformin inhibits lung cancer cell proliferation in a dose-dependent manner and promotes apoptotic cell death,as evidenced by metformin-induced PARP and caspase cleavage.Furthermore,the pan-caspase inhibitor z-VAD-fmk reverses metformin-induced cell death.Western blot and qPCR results suggest that metformin markedly downregulates RIP1 expression without affecting its mRNA and ubiquitination levels(0 vs 80 mmol/L,100%vs 20%,100%vs 15%).Additionally,co-immunoprecipitation and immunofluorescence results reveal that metformin may suppress RIP1 expression in an Hsp70-dependent manner,as metformin promotes Hsp70 degradation,and Hsp70 endogenously interacts with RIP1.Subsequent CCK-8,flow cytometry,and Western blot analyses suggest that metformin decreases Hsp70/RIP1 expression through AMPK/PKA/GSK-3βaxis.Consistently,results from a subcutaneous transplant tumor model indicate that metformin retards tumor growth without affecting mouse body weight.Collectively,these data highlight the part of RIP1 in metformin-induced anticancer activities in lung cancer in vitro and in vivo,providing novel strategy for lung cancer administration.
基金BioRender.com for the picture drawingEditage(www.editage.cn)for English language editing+2 种基金the Natural Science Foundation of Henan Province(Grant No.:252300421361)the National Natural Science Foundation of China(Grant No.:82000787)the Henan Medical Science and TechnologyResearch Program Project(Grant No.:SBGJ202102142).
文摘Renal tubular injury has emerged as a critical factor in the progression of diabetic kidney disease(DKD).Given renal tubules'high mitochondrial density and susceptibility to mitochondrial dysregulation and ferroptosis,targeting these pathways could offer therapeutic potential.Metformin(MET),a first-line therapy for type 2 diabetes mellitus(T2DM),exerts reno-protective effects by improving mitochon-drial function and attenuating fibrosis;however,its role in regulating ferroptosis in DKD remains unclear.This study aimed to investigate the role of MET in modulating mitophagy and ferroptosis in diabetic kidneys.In diabetic mouse models,MET notably alleviated tubular injury by promoting mitophagy and reducing ferroptosis,as shown by increasing levels of phosphatase and tensin homolog(PTEN)-induced putative kinase 1(PINK1)and Parkin,while decreased levels of malondialdehyde(MDA)and iron con-tent.Mechanistically,MET downregulated the hypoxia-inducible factor-1alpha(HIF-1α)/myo-inositol oxygenase(MIOX)signaling axis in renal tubular epithelial cells(RTECs),thereby restoring mitophagy and inhibiting ferroptosis.These findings demonstrate that MET mitigates diabetic renal injury by promoting mitophagy and countering ferroptosis via suppressing the HIF-1α/MIOX pathway,high-lighting its potential as a therapeutic intervention for halting DKD progression.
文摘Background:Diabetes,a metabolic disease marked by endocrine dysfunctions,significantly impacts oxidative stress pathways.This study explores the protective effects of lemongrass extract(LE),citral,and lemongrass extract-synthesized silver nanoparticles(LE-AgNP)against hyperglycemia-induced oxidative stress by modulating the Nrf2 pathway,which is crucial for antioxidant responses.Methods:Various techniques characterized the nanoparticles,including ultraviolet–visible spectroscopy,dynamic light scattering,zeta potential analysis,Fouriertransform infrared spectroscopy,scanning electron microscopy and transmission electron microscopy.Seventy rats,divided into seven groups,were used for in vivo experiments.Type 2 diabetes was induced using streptozotocin(65 mg/kg)and nicotinamide(90 mg/kg).After six weeks,biochemical parameters such as total antioxidant capacity,malondialdehyde,Nrf2,and Nrf2 miRNA were evaluated in pancreas tissue and blood serum,along with serum blood glucose levels.Results:LE-AgNP significantly improved weight gain,reduced food and water intake,and lowered blood glucose levels in diabetic rats.LE and citral did not significantly alter these parameters but prevented the decline in Nrf2 gene expression.LE-AgNP showed a significant increase in Nrf2 gene expression compared to the diabetic control group.Conclusions:This study highlights the potential of LE,citral,and especially LE-AgNP in mitigating oxidative stress induced by diabetes.LE-AgNP demonstrated superior therapeutic benefits,including improved oxidative stress conditions and hypoglycemic effects.
文摘Background:Polycystic ovary syndrome(PCOS)is one of the most common reproductive endocrine metabolic diseases.Combined use of metformin and diane-35 has better curative effect in regulating serum hormone level(LH,FSH,T and E2)than using metformin alone.Traditional Chinese medicine(TCM)can also be used to treat PCOS.According to some studies,the combined use of metformin and diane-35 and TCM have achieved better curative effect than combining metformin and diane-35 in the treatment of patients with PCOS.Methods:Computerized searches of the science,Medline,VIP,Wan Fang and China HowNet(CNKI)databases were conducted to identify eligible randomized controlled trials(RCTs)from the data obtained up to March 1,2022.The Cochrane Collaboration risk of bias tool was used to assess the risk of bias in individual RCTs,and R software(version 4.0.3)was used for data statistical analysis.Results:Nine RCTs involving 1035 patients were included.Comparing to D+M,significant reduce of LH(mean difference[MD]:-1.93,95%confidence interval[CI]:-3.44,-0.42;Unit:U/L P<0.01;I2=89%)、T(MD:-1.44,95%CI-2.59,-0.30;Unit:nmol/L P<0.01;I2=98%)and significant increase of E2(MD:31.43,95%CI 24.54,38.33;Unit:pmol/L P<0.01;I2=96%)were shown in TCM+D+M.Comparing to D+M,TCM+D+M group has higher ovulation rate(RR 1.1495%CI 1.07,1.22;P=0.42;I2=0%)and higher pregnancy rate(RR 1.2995%CI 1.15,1.44;P=0.37;I2=7%).There is no significant difference between the two therapies in FSH changes(MD:-1.00,95%CI-2.27,0.28;Unit:U/L P<0.01;I2=95%).Subgroup analysis showed that compared with the Guizhi Fuling capsule group,the Kuntai capsule group had more FSH reduction and E2 increase more.In other outcome indicators,the two subgroup did not show significant differences.Conclusion:Kuntai Capsule+Diane-35+Metformin is better than Guizhi Fuling Capsule in reducing FSH,and it is also better in increasing E2.There was no significant difference between the two in LH and T hormones.There was no significant difference between Kuntai Capsules+Diane-35+Metformin and Guizhi Fuling Capsules+Diane-35+Metformin.As for the effect in lessen insulin resistance,Kuntai Capsule+Diane-35+Metformin was significantly better than Guizhi Fuling Capsules+Diane-35+Metformin.
基金Supported by the Natural Science Research Project of Anhui Province,No.2023AH053172National Natural Science Foundation of Anhui Province,No.2408085QH260+1 种基金Projects of Administration of Traditional Chinese Medicine of Anhui Province,No.2024CCCX082National Natural Science Foundation Incubation Program of The Second Hospital of Anhui Medical University,No.2022GMFY08.
文摘Diabetes mellitus is a substantial global health threat due to its high prevalence and its serious complications.The hyperglycemic state causes damage to vascular endothelial cells and disturbance of lipid metabolism,thus contributing to the development of vascular disorders,especially atherosclerotic diseases.Aggressive glycemic control combined with vascular intervention is critical to the prevention and treatment of diabetes-associated atherosclerosis.It is suggested that metformin should be combined with hypoglycemic agents with proven vascular benefits for treating type 2 diabetes(T2DM)complicated with atherosclerotic diseases.Clinical studies indicates that the preferred combination is metformin with either glucagon-like peptide-1 receptor agonist or sodium/glucose cotransporter-2 inhibitor,which could offer additional vascular benefits and reduce the risk of atherosclerotic complications.Likewise,combination therapy with metformin and hypolipidemic agents has also shown additive effects on glucose control and lipid-lowering in patients with both diabetes and dyslipidemia,whereas extensive clinical trials using atherosclerotic-associated outcomes are required to support the vascular benefits.Moreover,co-administration of metformin with systemic antioxidant or anti-inflammatory therapy may also provide additional vascular benefits as indicated by several animal studies.For instance,a recent study found that additional supplementation of cholecalciferol and taurine enhanced metformin efficacy in controlling diabetes while reducing the risk of associated atherosclerotic complications.However,these potential benefits remain need validation by the evidence from clinical studies.Despite the limitations,such as heterogeneity across different patient populations,and deficiency in long-term outcomes,such efforts can contribute to finding optimal drug combinations to improve the management of T2DM and reduce its atherosclerotic complications.
文摘In recent years,the incidence of type 2 diabetes mellitus(T2DM)caused by obesity in China has been increasing continuously,which has become a risk factor for the onset of T2DM and seriously affects the quality of life of patients.The conventional treatment methods include weight loss and regulating the body’s metabolism.Semaglutide,as a glucagon-like peptide-1 receptor agonist(GLP-1RA),mainly reduces patients’appetite,decreases their craving for high-fat and high-sugar foods,regulates hypothalamic feeding behavior,inhibits gastric emptying and gastrointestinal motility,and ultimately leads to weight loss.Metformin mainly acts on extra-islet tissues,increasing glucose utilization,reducing glucose production,and ultimately lowering blood glucose levels.Based on this,this article reviews relevant literature on authoritative websites such as CNKI and Wanfang,organizes the data,and analyzes the research progress of semaglutide combined with metformin in the treatment of obese T2DM.The aim is to bring more treatment options for obese T2DM and promote better prognosis for patients.
文摘Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and therapeutic strategies remain unattainable.Recent studies have recognized the involvement of microRNA-155(miR-155)in the pathogenesis of OA and most of its risk factors while also identifying the antidiabetic drug metformin as a potential modulator of disease progression.MiR-155,a key endogenous regulator of the immune system,mechano-transduction,and multiple genetic pathways,interacts with OA targets of cellular energetic and circadian homeostasis,promoting systemic and local articular inflammation,cartilage matrix degradation,and chondrocyte apoptosis.Metformin,widely used for type 2 diabetes,has demonstrated anti-inflammatory,anti-oxidative,and chondroprotective properties in OA,mainly through its activation of adenosine monophosphate-activated protein kinase and inhibition of nuclear factor kappa-B signalling.Enthrallingly,metformin targets the same cellular pathways as miR-155 with emerging evidence also suggesting miR-155 expression modulation,indicating synergistic,potentially disease-modifying effects in OA.This review highlights the central role of miR-155 in OA pathophysiology and its potential as a biomarker for disease diagnosis and progression.MiR-155 targeting-through microRNA therapeutics(mimics/antagomiRs)and/or metformin-could pave the way for innovative treatments,including novel articular delivery systems and cell-based therapies.
文摘Metformin-induced vitamin B12 deficiency is a prevalent condition among pa-tients with type 2 diabetes mellitus.In recent years,a growing body of evidence has demonstrated the association between vitamin B12 deficiency and the onset,progression,and worsening of diabetic neuropathy(DNP)as well as its im-provement with supplementation in cases of deficiency.Major clinical guidelines for diabetes and DNP remain vague in their recommendations for B12 measu-rement and supplementation,and some guidelines do not address it at all.Given that vitamin B12 therapy is an economical,safe,and widely available treatment in most countries and supported by emerging evidence of its potential benefits,greater efforts should be made to promote systematic screening for vitamin B12 deficiency in all patients with DNP before establishing a definitive diagnosis as well as in patients with diabetes with risk factors for deficiency.Vitamin B12 deficiency should be treated in all affected patients,and supplementation should be considered in those with borderline levels when confirmatory diagnostic tests for deficiency are unavailable.Clinical guidelines should place greater emphasis on the recommendations for measuring and supplementing vitamin B12 in these patients.
基金funded by grants Pronaii 302979A1-S-9005 CONACyT (México) from RMDA。
文摘Dengue is an arboviral disease caused by the dengue virus,with 390 million infections reported annually worldwide.It is classified into two categories:dengue without or with warning signs and severe dengue.[1]Given the moderate efficacy of the dengue vaccine,[2]there is an urgent necessity to design host-directed therapeutic strategies,such as the repurposing of FDA-approved drugs,to combat dengue virus infection.
文摘In previous studies, compound mefformin/glipizide was developed. Aim To discover the mechanism of drug release from factors influencing drug release from dosage form （the semi-permeable cry orifice） were investigated. Results The influx of water that elementary osmotic pump tablet it. Methods Three rate-limiting membrane, tablet core and delivpassed the osmotic pump tablet was almost equal to the metformin release rate, while it was greatly less than the drug dissolution rate from tablet core. The size of orifice from 0. 4 mm to 0.8 mm had no influence on drug release. The osmotic pressure of tablet core was mainly caused by mefformin. Conclusion From the developed model of osmotic pump systems, it can be seen that only the water influx through the membrane is a rate-limiting step, not tablet core dissolution rate and solution influx, and only when the core dissolution rate is equal to the solution influx, the zero order release is seen in the osmotic pump systems.
文摘Aim In this study, compound metformin/glipizide bilayer extended release tablets were formulated with hydroxypropyl methylcellulose （HPMC） by wet granulation technique in order to tackle the problems associated with the muhidrug therapy of non-insulin dependent diabetes mellitus. Me^ls High-dose metformin is difficult to formulate into a tablet dosage form due to its poor compressibility and compactibility. In this study, the way to overcome the difficulty was to utilize stearic alcohol to prepare the tablet formulation. The influences of viscosity, amount of HPMC, and weight of fillers were investigated. The optimal formulation had acceptable physicochemical properties and released metformin and glipizide over 10 h. Results The data of metformin obtained from in vitro release fitted Higuchi kinetics best, while the release of glipizide in vitro was found to follow zero kinetics. Conclusion Compound metformin/glipizide bilayer extended release tablets have been successfully developed.
文摘Aim To prepare the prolonged-released microspheres of mefformin hydrochloride. Methods Ion-exchange resin-drug mefformin hydrochloride complexes were prepared as core materials, and followed by coating using ethylcellulose （EC） by the emulsion solvent diffusion technique. The release rate of mefformin from the microcapsules was highly dependent on the encapsulating formulation, thus being used as an index for formulation screening. Orthogonal experiments were performed to optimize the coating formulation. Results The final chosen formulation for coating of mefformin microcapsules were as follows： （ 1 ） the ratio of EC （20cps） to EC （45cps） was 50：50; （2） the ratio of plasticizer to coating materials was 20% ;and （3） the ratio of resin-mefformin complexes to coating materials was 5 ： 1. Conclusion The prolonged release microspheres of mefformin hydrochloride were successfully prepared.
文摘To date,metformin remains the first-line oral glucose-lowering drug used for the treatment of type 2 diabetes thanks to its well-established long-term safety and efficacy profile.Indeed,metformin is the most widely used oral insulinsensitizing agent,being prescribed to more than 100 million people worldwide,including patients with prediabetes,insulin resistance,and polycystic ovary syndrome.However,over the last decades several observational studies and meta-analyses have reported a significant association between long-term metformin therapy and an increased prevalence of vitamin B12 deficiency.Of note,evidence suggests that long-term and high-dose metformin therapy impairs vitamin B12 status.Vitamin B12(also referred to as cobalamin)is a water-soluble vitamin that is mainly obtained from animal-sourced foods.At the cellular level,vitamin B12 acts as a cofactor for enzymes that play a critical role in DNA synthesis and neuroprotection.Thus,vitamin B12 deficiency can lead to a number of clinical consequences that include hematologic abnormalities(e.g.,megaloblastic anemia and formation of hypersegmented neutrophils),progressive axonal demyelination and peripheral neuropathy.Nevertheless,no definite guidelines are currently available for vitamin B12 deficiency screening in patients on metformin therapy,and vitamin B12 deficiency remains frequently unrecognized in such individuals.Therefore,in this“field of vision”article we propose a list of criteria for a cost-effective vitamin B12 deficiency screening in metformin-treated patients,which could serve as a practical guide for identifying individuals at high risk for this condition.Moreover,we discuss additional relevant topics related to this field,including:(1)The lack of consensus about the exact definition of vitamin B12 deficiency;(2)The definition of reliable biomarkers of vitamin B12 status;(3)Causes of vitamin B12 deficiency other than metformin therapy that should be identified promptly in metformin-treated patients for a proper differential diagnosis;and(4)Potential pathophysiological mechanisms underlying metformin-induced vitamin B12 deficiency.Finally,we briefly review basic concepts related to vitamin B12 supplementation for the treatment of vitamin B12 deficiency,particularly when this condition is induced by metformin.
基金National Natural Science Foundation of China(Grant No.81373494)
文摘Drug transporters determine plasma and tissue exposure of a broad variety of drugs and play a critical role in drug-drug interaction （DDI）. In the present study, we aimed to investigate the effects of carvedilol on pharmacokinetics of metformin as well as the mechanism of their interaction. Results showed that plasma concentration of metformin was not significantly altered after single or 7-day co-administration of carvedilol, and the urinary excretion of metformin was also not influenced by carvedilol. However, the concentration of metformJn in the liver and kidney was markedly elevated. Similarly, carvedilol did not affect the renal elimination of metformin, but increased renal concentration in isolated kidney perfusion. On the other hand, carvedilol treatment did not affect the expressions of rOCTs and rMATE 1 in the liver and kidney of rats. After long-term co-administration, there were no differences in lactic acid （LCA）, uric acid （URIC） and creatinine （CREA） levels between two groups. These results indicated that carvedilol increased hepatic and renal distribution of metformin, resulting in local drug interaction.
文摘BACKGROUND Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes.Due to the lack of randomized control trials,most of the data pertaining to the clinical course,therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series.AIM To analyse the symptomology,clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series.METHODS We performed a systematic search from PubMed,Science Direct,Reference Citation Analysis(https://www.referencecitationanalysis.com/)and Google Scholar databases using the terms“metformin”AND“toxicity”OR“overdose”OR“lactic acidosis”OR“hyperlactatemia”.The inclusion criteria were:(1)Case reports or case series with individual patient details;and(2)Reported toxicity or overdose of metformin in adults,published in the English language.Data regarding baseline demographics,clinical presentation,therapeutic interventions,intensive care unit course and overall outcome were collected.RESULTS Two hundred forty-two individual cases were analysed,from 158 case reports and 26 case series,with a cumulative mortality of 19.8%.214(88.4%)patients were diabetics on metformin.57(23.6%)had acute ingestion,but a great majority(76.4%)were on metformin in therapeutic doses when they developed toxicity.Metformin associated lactic acidosis(MALA)was the most commonly reported adverse effect present in 224(92.6%)patients.Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia.The organ support used was renal replacement therapy(RRT)(68.6%),vasopressors(58.7%)and invasive mechanical ventilation(52.9%).A majority of patients(68.6%)received RRT for toxin removal,renal dysfunction and correction of MALA.Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT.CONCLUSION Most of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions.These patients may develop severe lactic acidosis,leading to significant morbidity and need for organ support.Despite severe MALA and the need for multiple organ support,they may have good outcomes,especially when RRT is used.The dose of metformin,serum pH,lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.
基金National Integrity Innovational Technology Platform of New Drug and Research and Development (Grant No.2009ZX09201-010)Innovation Team of Ministry of Education(Grant No. BMU20110263)
文摘An efficient and sensitive ion-pair HPLC-UV method using atenolol as internal standard （IS） was developed and validated for the determination of metformin in the plasma of diabetic rats. Plasma samples were deproteinated with 10% （v/v） perchloric acid. Separation was achieved on a UltimateTM AQ-C18 column （250 mm×4.6 mm, 5 μm） with a mobile phase （pH 5.05） composed of acetonitrile-water （31：69, v/v, containing 0.002 M sodium dodecyl sulfate, 0.0125 M potassium dihydrogen phosphate, 0.015 M triethylamine） at a flow rate of 1.0 mL/min. The calibration curve was linear （r〉0.994） between 7.5 and 4000 ng/mL. The lower limit of quantification （LLOQ） was 7.5 ng/mL. The precision was validated and the relative standard deviation was in the range of 1.87% to 15.70%; the accuracy was between 93.98%-106.89%. The mean recoveries were 95.40% and 95.31% for metformin and IS, respectively. The relative error （RE） of stability at different storage conditions was within ±9.00%. This method was used to determine the concentration-time profile of metformin in diabetic rat plasma following an oral administration of metformin at the dose of 10 mg/kg. Our results indicated that ion-pair HPLC-UV method using UltimateTM AQ-C18 column was effective for the pharmacokinetic studies of high polarity compounds like metformin.
