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Metformin has been widely used for over 5 decades. New preparations have been developed for possible enhancement of efficiency, tolerability, and pleiotropic nonglycemic effects. Extended-release metformin has contributed to adher...
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Metformin has been widely used for over 5 decades. New preparations have been developed for possible enhancement of efficiency, tolerability, and pleiotropic nonglycemic effects. Extended-release metformin has contributed to adherence and improved gastrointestinal tolerability. Delayed-release metformin acts in the lower gastrointestinal tract and exerts glucose-lowering effects at lower plasma metformin levels, which might suggest use of this biguanide in patients with chronic kidney disease. Metformin is also known to have numerous nonglycemic effects. Results of the UK Prospective Diabetes Study indicate improvements in cardiovascular outcome and reduced total mortality independent of glycemic control. Anticancer effects of metformin have been discussed and many clinical trials are on-going. Metformin is noted for its beneficial effects on lifespan extension and on disorders due to increased insulin resistance. Further investigations, including randomized control trials in nondiabetic individuals, are required to demonstrate the nonglycemic effects of metformin.
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Background: Metformin (Mf) (N, N'-Dimethylbiguanide) is used as the first-line medication for treating diabetes mellitus type II. It is also considered as a "gold standard" treatment for various diseases like hyperglycemia, insuli...
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Background: Metformin (Mf) (N, N'-Dimethylbiguanide) is used as the first-line medication for treating diabetes mellitus type II. It is also considered as a "gold standard" treatment for various diseases like hyperglycemia, insulin resistance, infertility, cardiovascular disease, renal dysfunction, polycystic ovary syndrome, obesity, cancer and ageing. Majority of the methods available for quantitative analysis of Mf are expensive, time-consuming, require sample pre-treatment and skilled persons to operate. Electrochemical sensors overcome these drawbacks, as these are fast, simple, cost-effective, specific and highly sensitive.
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The aim of this study was to evaluate if the new metformin powder formulation improves the treatment satisfaction in patients with type 2 diabetes, in a case-control clinical trial. We enrolled 602 subjects in therapy with metform...
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The aim of this study was to evaluate if the new metformin powder formulation improves the treatment satisfaction in patients with type 2 diabetes, in a case-control clinical trial. We enrolled 602 subjects in therapy with metformin in tablets formulation and instructed them to take the same dose of metformin in the new powder formulation. At baseline, and after 6 months since the assumption of metformin powder, each patient answered the following questionnaires: the SF-36 Health Survey, the Diabetes Quality Of Life questionnaire Modified (DQOL/Mod), and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). We also assessed the following at baseline, at 3 and 6 months: fasting plasma glucose (FPG) and postprandial glucose (PPG), glycated hemoglobin (HbA(1c)), fasting plasma insulin (FPI), and homeostasis model assessment index of insulin resistance (HOMA-IR). We observed a statistically significant reduction in HbA(1c), FPG, PPG, FPI, and HOMA-IR (P <. 05 for all) with metformin powder. The DTSQ questionnaire showed a higher level of satisfaction linked to the assumption of metformin powder compared to the tablets formulation. In conclusion, metformin powder formulation seems to be more appropriate for the treatment of diabetic patients. The improvement of glycemic control suggests a better adherence to the powder formulation.
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Objective: To describe a case of postmenopausal hyperandrogenemia in which a small ovarian tumor was ruled out by a positive metformin suppression test.Methods: We present the clinical, laboratory, and pathologic findings and the ...
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Objective: To describe a case of postmenopausal hyperandrogenemia in which a small ovarian tumor was ruled out by a positive metformin suppression test.Methods: We present the clinical, laboratory, and pathologic findings and the response to metformin.Results: A 52-year-old obese, postmenopausal, insulin resistant, female presented with hyperandrogenemia. With metformin therapy the testosterone level dropped by 76.9% and almost normalized. The positive result of the metformin suppression test was consistent with the diagnosis of postmeno-pause ovarian stromal hyperplasia, which was confirmed following bilateral oophorectomy.Conclusion: This case illustrates that in postmenopausal females with hyperandrogenemia the metformin suppression test may be helpful in eliminating a small ovarian tumor as a cause.
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ImportanceConsensus around an efficient second-line treatment option for type 2 diabetes (T2D) remains ambiguous. The availability of electronic medical records and insurance claims data, which capture routine medical practice, ac...
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ImportanceConsensus around an efficient second-line treatment option for type 2 diabetes (T2D) remains ambiguous. The availability of electronic medical records and insurance claims data, which capture routine medical practice, accessed via the Observational Health Data Sciences and Informatics network presents an opportunity to generate evidence for the effectiveness of second-line treatments.ObjectiveTo identify which drug classes among sulfonylureas, dipeptidyl peptidase 4 (DPP-4) inhibitors, and thiazolidinediones are associated with reduced hemoglobin A<sub>1c</sub>(HbA<sub>1c</sub>) levels and lower risk of myocardial infarction, kidney disorders, and eye disorders in patients with T2D treated with metformin as a first-line therapy.Design, Setting, and ParticipantsThree retrospective, propensity-matched, new-user cohort studies with replication across 8 sites were performed from 1975 to 2017. Medical data of 246?558?805 patients from multiple countries from the Observational Health Data Sciences and Informatics (OHDSI) initiative were included and medical data sets were transformed into a unified common data model, with analysis done using open-source analytical tools. Participants included patients with T2D receiving metformin with at least 1 prior HbA<sub>1c</sub>laboratory test who were then prescribed either sulfonylureas, DPP-4 inhibitors, or thiazolidinediones. Data analysis was conducted from 2015 to 2018.ExposuresTreatment with sulfonylureas, DPP-4 inhibitors, or thiazolidinediones starting at least 90 days after the initial prescription of metformin.Main Outcomes and MeasuresThe primary outcome is the first observation of the reduction of HbA<sub>1c</sub>level to 7% of total hemoglobin or less after prescription of a second-line drug. Secondary outcomes are myocardial infarction, kidney disorder, and eye disorder after prescription of a second-line drug.ResultsA total of 246?558?805 patients (126?977?785 women [51.5%]) were analyzed. Effectiveness of sulfonylureas, DPP-4 inhibitors, and thiazolidinediones prescribed after metformin to lower HbA<sub>1c</sub>level to 7% or less of total hemoglobin remained indistinguishable in patients with T2D. Patients treated with sulfonylureas compared with DPP-4 inhibitors had a small increased consensus hazard ratio of myocardial infarction (1.12; 95% CI, 1.02-1.24) and eye disorders (1.15; 95% CI, 1.11-1.19) in the meta-analysis. Hazard of observing kidney disorders after treatment with sulfonylureas, DPP-4 inhibitors, or thiazolidinediones was equally likely.Conclusions and RelevanceThe examined drug classes did not differ in lowering HbA<sub>1c</sub>and in hazards of kidney disorders in patients with T2D treated with metformin as a first-line therapy. Sulfonylureas had a small, higher observed hazard of myocardial infarction and eye disorders compared with DPP-4 inhibitors in the meta-analysis. The OHDSI collaborative network can be used to conduct a large international study examining the effectiveness of second-line treatment choices made in clinical management of T2D.
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A simple, selective, sensitive and precise high-performance liquid chromatographic plasma assay for the hypoglycemic agent metformin is described. Acidified samples of plasma were deproteinated with acetonitrile, washed with dichl...
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A simple, selective, sensitive and precise high-performance liquid chromatographic plasma assay for the hypoglycemic agent metformin is described. Acidified samples of plasma were deproteinated with acetonitrile, washed with dichloromethane and the resulting supernatant injected. Chromatography was performed at 40 deg C by pumping a mobile phase of acetonitrile (250 ml) in pH 7, 0.03 M diammonium hydrogen phosphate buffer (750 ml) at a flow-rate of 1 ml/min through a silica column. Metformin and the interanl standard (atenolol) were detected at 240 nm and were eluted 7.8 and 6.8 min, respectively, after injection. No endogenous substances were found to interfere. Calibration curves were linear (r > 0.999) from 10 to 2000 ng/ml. The absolute recovery of both metformin and atenolol was greater than 76%. The detection limit and limit of quantitation were 2.5 and 10 ng/ml, respectively. The intra- and inter- day precision (C.V.) was 12%, or less, and the accuracy was within 6.2% of the nominal concentration. This method is suitable for clinical investigation and monitoring metformin concentration.
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This article describes the development of the first ion pair solid phase extraction technique (IPSPE), which has been applied to the extraction of metformin from plasma samples. In addition an ion pair chromatographic method was d...
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This article describes the development of the first ion pair solid phase extraction technique (IPSPE), which has been applied to the extraction of metformin from plasma samples. In addition an ion pair chromatographic method was developed for the specific HPLC determination of metformin. Several extraction and HPLC methods have been described previously for metformin, however, most of them did not solve the problems associated with the high polarity of this drug. Drug recovery in the developed method was found to be more than 98%. The limit of detection and limit of quantification was 3 and 5 ng/ml, respectively. The intraday and interday precision (measured by coefficient of variation, CV%) was always less than 9%. The accuracy (measured by relative error, R.E.%) was always less than 6.9%. Stability analysis showed that metformin is stable for at least 3 months when stored at -70 ℃. The method has been applied to 150 patient samples as part of a medication adherence study.
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A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS-MS) method for the determination of metformin in human plasma using phenformin as internal standard has been developed and validated. Sample preparation ...
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A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS-MS) method for the determination of metformin in human plasma using phenformin as internal standard has been developed and validated. Sample preparation of plasma involved acidification with acetic acid, deproteination with acetonitrile and washing with dichloromethane. Samples were then analyzed by HPLC on a short Nucleosil C_(18) column (5 μm, 50 mm * 4.6 mm i.d.) using a mobile phase consisting of acetonitrile:methanol:10 mM ammonium acetate pH 7.0 (20:20:60, v/v/v) delivered at 0.65 ml/min. Detection was performed using an Applied Biosystems Sciex API 4000 mass spectrometer set at unit resolution in the multiple reaction monitoring (MRM) mode. Atmospheric pressure chemical ionization (APCI) was used for ion production. The assay was linear over the range 1-2000 ng/ml with intra- and inter-day precision of <8.6% and accuracy in the range 91-110%. The limit of detection was 250 pg/ml in plasma. The method was successfully applied to a clinical pharmacokinetic study of an extended-release tablet of metformin hydrochloride (500 mg) administered as a single oral dose.
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A rapid, sensitive and specific liquid chromatography-tandem mass spectrometry method is described for quantitation of metformin in human plasma. After a simple, one-step protein precipitation using acetonitrile, metformin and the...
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A rapid, sensitive and specific liquid chromatography-tandem mass spectrometry method is described for quantitation of metformin in human plasma. After a simple, one-step protein precipitation using acetonitrile, metformin and the internal standard diphenhydramine were chromatographed on a C8 column and detected by tandem mass spectrometry. An atmospheric pressure chemical ionization interface was chosen to reduce ion suppression from sample matrix components and provide high sensitivity. The method has a chromatographic total run time of 3.4 min and was linear within the range 2–2000 ng/ml. Intra- and inter-day precision, expressed as the relative standard deviation (R.S.D.), ranged from 4.4 to 5.7% and from 1.3 to 2.8%, respectively. Assay accuracy was less than 1% in terms of %RE (relative error). The assay was used to evaluate the pharmacokinetics of metformin after an oral administration of multicomponent formulation containing 500 mg metformin and 2.5 mg glyburide to 20 healthy volunteers.
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A rapid and simple high-performance liquid chromatographic (HPLC) assay for the determination of metformin in human plasma and breast milk is described. After proteins were precipitated with acetonitrile, metformin and the interna...
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A rapid and simple high-performance liquid chromatographic (HPLC) assay for the determination of metformin in human plasma and breast milk is described. After proteins were precipitated with acetonitrile, metformin and the internal standard buformin were resolved on a cation-exchange column and detected by UV detection at 236 nm. Standard curves were linear over the concentration range 20.0-4000 μg/l. Intra- and inter-day coefficients of variation were <9.0% and the limit of quantification was around 20 μg/l.
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