Metformin

Source: www.ncbi.nlm.nih.gov --- 7 days ago
Related Articles Metformin therapy and clinical uses. Diab Vasc Dis Res. 2008 Sep;5(3):157-67 Authors: Scarpello JH, Howlett HC Metformin is now established as a first-line antidiabetic therapy for the management of type 2 diabetes. Its early use in treatment algorithms is supported by lack of weight gain, low risk of hypoglycaemia and its mode of action to counter insulin resistance. The drug's anti-atherosclerotic and cardioprotective effects have recently been confirmed in prospective and retrospective studies, and appear to reflect a collection of glucose-independent effects on the vascular endothelium, suppressant effects on glycation, oxidative stress and formation of adhesion molecules, stimulation of fibrinolysis and favourable effects on the lipid profile. Although avoidance of troublesome gastrointestinal tolerability issues requires careful dose titration, the risk of serious adverse events is considered low provided that contra-indications (especially with respect to renal function) are observed. As many of its actions go beyond glucose lowering, emerging evidence indicates potential benefits in other insulin-resistant states and possibly tumour suppression. PMID: 18777488 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 6 hours ago
Related Articles Clinical development of Metformin extended-release tablets for type 2 diabetes: an overview. Expert Opin Drug Metab Toxicol. 2008 Sep;4(9):1235-43 Authors: Schwartz SL, Gordi T, Hou E, Cramer M, Heritier M, Cowles VE Glumetz (Depomed, Inc., Menlo Park, CA, USA) is a recently approved gastric retentive extended-release formulation of Metformin (M-ER) that provides effective, sustained and well-tolerated glycemic control with once daily administration. Pharmacokinetic studies have demonstrated a similar bioavailability of M-ER administered once daily to immediate-release Metformin given twice daily. In addition, M-ER has demonstrated a nearly linear dose proportionality with a relative bioavailability of highest dose to lowest dose of 80%, whereas with immediate-release Metformin the relative bioavailability of the highest dose to the lowest dose is only 58%. M-ER demonstrated a positive food effect and should be administered with a meal, preferably the evening meal. Because Metformin is only eliminated through renal mechanisms, the use of M-ER, as is the case with other formulations, is contraindicated in patients with renal impairment. Administration of M-ER with sulfonylureas (SUs) had no effect on the pharmacokinetics of Metformin. In controlled clinical trials M-ER demonstrated efficacy for 24 weeks as a monotherapy or in combination with SU. Additionally, glycemic control was maintained for an extra 24 weeks in a ...

Source: www.ncbi.nlm.nih.gov --- 7 days ago
Related Articles Metformin: a multitasking medication. Diab Vasc Dis Res. 2008 Sep;5(3):156 Authors: Bailey CJ PMID: 18777487 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 10 days ago
Related Articles The effect of Metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance. Equine Vet J. 2008 Jul;40(5):493-500 Authors: Durham AE, Rendle DI, Newton JE REASONS FOR PERFORMING STUDY: Laminitis in equids is a very common debilitating disease, and insulin resistance (IR) and hyperinsulinaemia are increasingly recognised as important predisposing factors. Pharmacological modification of IR and hyperinsulinaemia might reduce the risk of laminitis. HYPOTHESIS: Metformin, a drug commonly prescribed for treatment of human IR, may also decrease IR in equids. METHODS: Eighteen horses and ponies with IR and recurrent laminitis were treated with 15 mg/kg bwt Metformin per os q. 12 h. Each animal served as its own control by comparing pre- and post treatment proxies for IR, insulin sensitivity (IS) and pancreatic beta cell function while controlling for possible dietary and managemental influences on IR. RESULTS: Evidence of significantly improved IS and decreased pancreatic beta cell secretion was found following Metformin treatment. The magnitude of effect was greater at earlier resampling (6-14 days) than at later times (23-220 days). Apparent subjective clinical benefits were good but less favourable than effects on IR. CONCLUSIONS: Metformin is safe and appears to increase IS in equids. POTENTIAL RELEVANCE: Metformin may be indicated as a treatment for IR in equids. ...

Source: www.ncbi.nlm.nih.gov --- 10 days ago
Related Articles Prevention of Diabetes in Women with a History of Gestational Diabetes: Effects of Metformin and Lifestyle Interventions. J Clin Endocrinol Metab. 2008 Sep 30; Authors: Ratner RE, Christophi CA, Metzger BE, Dabelea D, Bennett PH, Pi-Sunyer X, Fowler S, Kahn SE, Context: A past history of gestational diabetes mellitus (GDM) confers a very high risk of post-partum development of diabetes, particularly type 2 diabetes. Objective: The Diabetes Prevention Program (DPP) sought to identify individuals with impaired glucose tolerance (IGT) and intervene in an effort to prevent or delay their progression to diabetes. This analysis examines the differences between women enrolled in DPP with and without a reported history of GDM. Design: The DPP was a randomized, controlled clinical trial. Setting: The study was a multicenter, NIH-sponsored trial carried out at 27 centers including academic and Indian Health Services sites. Patients: 2190 women were randomized into the DPP and provided information for past history of GDM. This analysis addresses the differences between those 350 women providing a past history of GDM and those 1416 women with a previous live birth, but no history of GDM. Interventions: Subjects were randomized to either standard lifestyle and placebo or Metformin therapy, or to an intensive lifestyle intervention. Main Outcomes: The primary outcome was the time to development of diabetes ascertained by semi-annua ...

Source: www.ncbi.nlm.nih.gov --- 5 days ago
Related Articles Prevalence of risk determinants for Metformin-associated lactic acidosis and Metformin utilization in the study of health in pomerania. Horm Metab Res. 2008 Jul;40(7):491-7 Authors: Runge S, Alte D, Baumeister SE, Völzke H Risk determinants for the life threatening complication of Metformin-associated lactic acidosis are frequently disregarded. Our first aim was to investigate the prevalence of risk determinants in subjects with type 2 diabetes mellitus (DM2) taking Metformin compared to subjects with nonmetformin treatment. Our second aim was to estimate the proportion of subjects with alternative drug-treatment, and no risk determinants, which would probably benefit from Metformin. The Study of Health in Pomerania is a population-based health survey including 322 DM2 subjects. Risk determinants were assessed by personal interview, ultrasound, and laboratory analysis. Among the subjects with DM2 n=92 (28.6%) were treated with Metformin, n=162 (50.3%) with alternative medication, and n=68 (21.1%) with diet. The prevalence of at least one risk determinant was 62% for Metformin-users. There was no difference in number and type of risk determinants. Heart failure, angina pectoris, and liver disorders presented the most frequent risk determinants. Current risk determinants for Metformin-associated lactic acidosis are largely disregarded. Improved selection of patients can result in safe Metformin utilization in one quarter ...

Source: www.ncbi.nlm.nih.gov --- 5 days ago
Related Articles Dehydroepiandrosterone and Metformin modulate progesterone-induced blocking factor (PIBF), cyclooxygenase 2 (COX2) and cytokines in early pregnant mice. J Steroid Biochem Mol Biol. 2008 Sep;111(3-5):200-7 Authors: Luchetti CG, Mikó E, Szekeres-Bartho J, Paz DA, Motta AB The present study examined the mechanism by which Metformin (N,N'-dimethylbiguanide) prevents embryonic resorption induced in mice by dehydroepiandrosterone (DHEA). Treatment with DHEA (60mg/kg, s.c. 24 and 48h post-implantation) induces embryo resorption of early pregnant BALB/c mice while simultaneous treatment with Metformin (240mg/kg, oral 24 and 48h post-implantation) prevents it. During pregnancy progesterone-induced blocking factor (PIBF) modulates prostaglandins (PGs) and cytokine production. These findings prompted us to investigate the effect of DHEA and Metformin on both PIBF and cyclooxygenase 2 (COX2) expressions at the implantation sites, as well as cytokine production. PIBF and COX2 expression were detected by immunohistochemistry from DHEA and DHEA+ Metformin treated 8 days-pregnant mice and serum cytokine levels of these animals were determined by ELISA. DHEA treatment both abolished PIBF expression and increased COX2 expression. Embryo resorption correlates with the lack of PIBF expression, diminished IL-6 levels and increased IL-2 concentration while Metformin was able to reverse the effect of DHEA on both PIBF and COX2 expression and ...

Source: www.ncbi.nlm.nih.gov --- 7 days ago
Related Articles Improvement of glycaemic and lipid profiles with muraglitazar plus Metformin in patients with type 2 diabetes: an active-control trial with glimepiride. Diab Vasc Dis Res. 2008 Sep;5(3):168-76 Authors: Rubin CJ, Ledeine JM, Fiedorek FT The efficacy and safety of muraglitazar versus glimepiride were evaluated in patients with type 2 diabetes. After open-label Metformin monotherapy, 1,805 patients received randomised therapy with muraglitazar 2.5 mg or 5 mg or with glimepiride 1 mg in a double-blind 52-week study. The primary end point was change in glycosylated haemoglobin (HbA1C); secondary end points were changes in fasting lipid levels and glycaemic indices. At week 52, the reduction in HbA1C with muraglitazar 5 mg plus Metformin was superior (p<0.0001) and with muraglitazar 2.5 mg it was non-inferior in comparison with glimepiride. At week 12, muraglitazar significantly decreased triglyceride levels (p<0.0001) and increased levels of high-density lipoprotein cholesterol (HDL-C) (p<0.0001). Oedema, weight gain and heart failure were more evident with muraglitazar. Muraglitazar 5 mg plus Metformin significantly improved HbA1C, triglyceride and HDL-C levels in patients with type 2 diabetes. Cardiovascular events were similar among groups (~2%), but there was an imbalance of total mortality in favour of glimepiride. PMID: 18777489 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 10 days ago
Related Articles Achieving glycosylated hemoglobin targets using the combination of repaglinide and Metformin in type 2 diabetes: a reanalysis of earlier data in terms of current targets. Clin Ther. 2008 Mar;30(3):552-4 Authors: Moses RG BACKGROUND: For patients with type 2 diabetes, the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) currently recommend a glycosylated hemoglobin (HbA(1c) ) target of <7%, and the British Medical Association (BMA) Quality and Outcomes Framework recommends an HbA(1c) target of >or=7.5%. OBJECTIVE: This letter presents a reanalysis of data from a previous study of the effect on glycemic control of adding repaglinide to Metformin monotherapy in patients with type 2 diabetes to determine the proportion of patients achieving current ADA/EASD and BMA targets. METHODS: PubMed was searched using the terms repaglinide AND Metformin AND HbA(1c) to identify published comparisons of monotherapy and combination therapy with these drugs in patients with type 2 diabetes. RESULTS: In the original analysis, which employed an HbA(1c) target of <7.1%, 59%of patients treated with Metformin plus repaglinide achieved their glycemic target, compared with approximately 20% of patients treated with Metformin or repaglinide alone. On reanalysis of the data according to the current ADA/EASD HbA(1c) target of <7%, 56% of patients receiving Metformin and repaglinide achieved that goal,c ...

Source: www.ncbi.nlm.nih.gov --- 6 hours ago
Related Articles [Effect of lifestyle adjustment, Metformin and rosiglitazone in polycystic ovary syndrome] Zhonghua Fu Chan Ke Za Zhi. 2007 May;42(5):294-7 Authors: Ma LK, Jin LN, Yu Q, Xu L OBJECTIVE: To compare the efficacy of weight loss, Metformin and rosiglitazone in women with polycystic ovary syndrome (PCOS). METHODS: A randomized controlled trial (RCT) was carried out in Peking Union Medical College Hospital (PUMCH), one hundred and six women with PCOS were assigned to three intervention groups: weight loss, weight loss and Metformin, weight loss and rosiglitazone group. Patients were treated with weight loss (diet and exercise), weight loss and Metformin (500 mg three times daily), weight loss and rosiglitazone (4 mg once daily) for three months. Sixty patients completed treatments. Basal body temperature (BBT), total testosterone as well as fasting serum insulin levels and lipid were measured and compared in all patients before and after weight loss. RESULTS: No significant differences were found in the baseline characteristics among three groups. In weight loss group 51% (22/43) patients completed treatment, and 23% (5/22) patients resumed ovulation. In weight loss and Metformin group 58% (21/36) patients completed treatment, and 43% (9/21) patients resumed ovulation. In weight loss and rosiglitazone group 63% (17/27) patients completed treatment, and 59% (10/17) patients resumed ovulation. Ovulation rate was significantl ...

Source: www.ncbi.nlm.nih.gov --- 8 days ago
Related Articles Considerations regarding the use of Metformin with olanzapine. Am J Psychiatry. 2008 Sep;165(9):1205-6; author reply 1207 Authors: Alamiri B PMID: 18765498 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 31 days ago
Related Articles [Metformin and kidneys] Vnitr Lek. 2008 May;54(5):535-40 Authors: Smahelová A Metformin is currently recommended as the first-line drug for type 2 diabetic patients once the disease has been diagnosed. In addition to antihyperglycaemic effect, it has other effects which have a positive effect on cardiovascular risk. The greatest risk of Metformin treatment is lactate acidosis, but its incidence is very low if the contraindications are observed. In spite of the fact that not all contraindications are observed in practice, the incidence of lactate acidosis demonstrably provoked by Metformin does not grow. In spite of ongoing discussion on the subject, contraindications still include all states involving the risk of lactacidosis including renal insufficiency. PMID: 18630642 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 15 days ago
Extended-release Metformin in Asian patients. Int J Clin Pract. 2008 May;62(5):669-70 Authors: Naser KA PMID: 18412927 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 26 days ago
Related Articles Dehydroepiandrosterone and Metformin regulate proliferation of murine T lymphocytes. Clin Exp Immunol. 2008 Aug;153(2):289-96 Authors: Solano ME, Sander V, Wald MR, Motta AB The aim of the present study was to assess the effect of dehydroepiandrosterone (DHEA: 10 microM) and Metformin (10 microM and 100 microM) in regulating proliferation of cultured T lymphocytes. T cells were isolated from lymph nodes of prepuberal BALB/c mice. We found that DHEA, Metformin and DHEA + Metformin added to the incubation media diminished proliferation of T cells. The inhibition by DHEA was higher than that produced by Metformin, while the combined treatment showed a synergistic action that allowed us to speculate distinct regulatory pathways. This was supported later by other findings in which the addition of DHEA to the incubation media did not modify T lymphocyte viability, while treatment with Metformin and DHEA + Metformin diminished cellular viability and increased both early and late apoptosis. Moreover, DHEA diminished the content of the anti-oxidant molecule glutathione (GSH), whereas M and DHEA + Metformin increased GSH levels and diminished lipid peroxidation. We conclude that DHEA and Metformin diminish proliferation of T cells through different pathways and that not only the increase, but also the decrease of oxidative stress inhibited proliferation of T cells, i.e. a minimal status of oxidative stress, is necessary to trigg ...

Source: www.ncbi.nlm.nih.gov --- 31 days ago
Related Articles Reverse of progestin-resistant atypical endometrial hyperplasia by Metformin and oral contraceptives. Obstet Gynecol. 2008 Aug;112(2 Pt 2):465-7 Authors: Shen ZQ, Zhu HT, Lin JF BACKGROUND: Atypical endometrial hyperplasia usually is treated with high-dose progestin or hysterectomy, but the latter deprives the patient of future child bearing. CASES: Two women with atypical endometrial hyperplasia complicating polycystic ovary syndrome (PCOS) had failed to respond to high-dose progestin therapy. They were both obese, insulin-resistant, and nulliparous with a desire to preserve fecundity. Metformin and oral contraceptives were administered as alternatives. Endometrial curettage performed 3 months later demonstrated a proliferative endometrium without evidence of residual pathology. CONCLUSION: Insulin resistance might play a role in the occurrence of atypical endometrial hyperplasia complicating PCOS. Metformin and oral contraceptives could be an alternative treatment in the presence of progestin resistance. PMID: 18669766 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 24 days ago
Related Articles Heeding clues to Metformin-associated lactic acidosis: prompt response can save life. Emerg Med J. 2008 Aug;25(8):537-8 Authors: Kumar U, Chennavir B, Gopi A The case history is presented of a patient who developed Metformin-associated lactic acidosis. The patient made a complete recovery with supportive care. Recognition of Metformin-associated lactic acidosis requires a high index of suspicion as presentation can be very subtle. PMID: 18660415 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 31 days ago
Related Articles Metformin induces cardioprotection against ischaemia/reperfusion injury in the rat heart 24 hours after administration. Basic Clin Pharmacol Toxicol. 2008 Jul;103(1):82-7 Authors: Solskov L, Løfgren B, Kristiansen SB, Jessen N, Pold R, Nielsen TT, Bøtker HE, Schmitz O, Lund S The UK Prospective Diabetes Study demonstrated that the hypoglycaemic drug Metformin is associated with a reduction in cardiovascular events in a group of obese type 2 diabetes patients. The energy sensing enzyme AMP-activated protein kinase (AMPK) has been indicated to play an important protective role in the ischaemic heart and is activated by Metformin. The aim of this study was to determine whether a single dose of Metformin protects the myocardium against experimentally induced ischaemia 24 hr after the administration, and furthermore to determine whether a single dose of Metformin results in an acute increase in myocardial AMPK activity. Wistar rats were given either a single oral dose of Metformin (250 mg/kg body weight), or a single oral dose of saline. After 24 hr, the hearts were Langendorff-perfused and subjected to 45 min. of coronary artery occlusion. Infarct size was determined by staining with triphenyltetrazoliumchloride (TTC) and Evans Blue and expressed as a percentage of the risk zone (IS/AAR %). Isoform specific AMPK activity was measured 2 hr after administration of Metformin or saline. Infarct size was significantly reduced ...

Source: www.ncbi.nlm.nih.gov --- 37 days ago
Related Articles Effects of pioglitazone and Metformin on NEFA-induced insulin resistance in type 2 diabetes. Diabetologia. 2008 Sep 4; Authors: Basu R, Basu A, Chandramouli V, Norby B, Dicke B, Shah P, Cohen O, Landau BR, Rizza RA AIMS/HYPOTHESIS: We sought to determine whether pioglitazone and Metformin alter NEFA-induced insulin resistance in type 2 diabetes and, if so, the mechanism whereby this is effected. METHODS: Euglycaemic-hyperinsulinaemic clamps (glucose approximately 5.3 mmol/l, insulin approximately 200 pmol/l) were performed in the presence of Intralipid-heparin (IL/H) or glycerol before and after 4 months of treatment with pioglitazone (n = 11) or Metformin (n = 9) in diabetic participants. Hormone secretion was inhibited with somatostatin in all participants. RESULTS: Pioglitazone increased insulin-stimulated glucose disappearance (p < 0.01) and increased insulin-induced suppression of glucose production (p < 0.01), gluconeogenesis (p < 0.05) and glycogenolysis (p < 0.05) during IL/H. However, glucose disappearance remained lower (p < 0.05) whereas glucose production (p < 0.01), gluconeogenesis (p < 0.05) and glycogenolysis (p < 0.05) were higher on the IL/H study day than on the glycerol study day, indicating persistence of NEFA-induced insulin resistance. Metformin increased (p < 0.001) glucose disappearance during IL/H to rates present during glycerol treatment, indicating protection against NEFA-induced insulin res ...

Source: www.ncbi.nlm.nih.gov --- 28 days ago
Related Articles Metformin, B12 and homocysteine levels: the plausible cause or effect? J Formos Med Assoc. 2008 Jun;107(6):505-6; author reply 507 Authors: Musarrat K, Kalathil D, Varughese GI PMID: 18583223 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 26 days ago
Related Articles Metformin use in polycystic ovary syndrome: metabolic benefits and diabetes prevention. Am J Med. 2008 Aug;121(8):e9; author reply e11 Authors: Goodarzi MO, Azziz R PMID: 18691471 [PubMed - indexed for MEDLINE] ...