Metformin scientific update |
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Diabetes Care. 2010 Jul;33(7):1484-90.
Chatterjee R, Narayan KM, Lipscomb J, Phillips LS.
Corresponding author: Ranee Chatterjee, rchatte2@jhu.edu.
Screening adults for pre-diabetes and diabetes may be cost-saving.
OBJECTIVE The economic costs of hyperglycemia are substantial. Early detection would allow management to prevent or delay development of diabetes and diabetes-related complications. We investigated the economic justification for screening for pre-diabetes/diabetes. RESEARCH DESIGN AND METHODS We projected health system and societal costs over 3 years for 1,259 adults, comparing costs associated with five opportunistic screening tests. All subjects had measurements taken of random plasma and capillary glucose (RPG and RCG), A1C, and plasma and capillary glucose 1 h after a 50 g oral glucose challenge test without prior fasting (GCT-pl and GCT-cap), and a subsequent diagnostic 75 g oral glucose tolerance test (OGTT). RESULTS Assuming 70% specificity screening cutoffs, Medicare costs for testing, retail costs for generic metformin, and costs for false negatives as 10% of reported costs associated with pre-diabetes/diabetes, health system costs over 3 years for the different screening tests would be GCT-pl $180,635; GCT-cap $182,980; RPG $182,780; RCG $186,090; and A1C $192,261; all lower than costs for no screening, which would be $205,966. Under varying assumptions, projected health system costs for screening and treatment with metformin or lifestyle modification would be less than costs for no screening as long as disease prevalence is at least 70% of that of our population and false-negative costs are at least 10% of disease costs. Societal costs would equal or exceed costs of no screening depending on treatment type. CONCLUSIONS Screening appears to be cost-saving compared to no screening from a health system perspective, and potentially cost-neutral from a societal perspective. These data suggest that strong consideration should be given to screening-with preventive management-and that use of GCTs may be cost-effective.
Arh Hig Rada Toksikol. 2010 Jun 1;61(2):241-245.
Rogulj D, Hauptfeld M, Iskra MS, Zorko VK, Strašek M.
Department of Internal Medicine, General Hospital Brezice, Brezice, Slovenia.
Extreme Hyperkalaemia Caused by Concomitant use of a Nsaid and an Ace Inhibitor in an Elderly Patient.
Extreme hyperkalaemia is a life-threatening electrolyte disorder. It is relatively common in patients with severe renal insufficiency. This report describes a case of extreme hyperkalaemia caused by drugs in an 82-year-old female patient without severe renal insufficiency, who was successfully treated without haemodialysis. The patient had been treated for arterial hypertension and type 2 diabetes mellitus for 30 years. Over the last years she had been receiving enalapril and metformin. Three weeks before the admission to the hospital, she was receiving a non-steroidal anti-inflammatory drug (NSAID) because of the back pain. She was admitted to hospital due to a collapse and weakness in the limbs. Laboratory tests showed extreme hyperkalaemia, high blood sugar, metabolic acidosis, elevated serum creatinine and blood urea nitrogen (BUN), and a slightly elevated serum sodium. On ECG, we noticed typical signs of hyperkalaemia.The patient was treated with a slow intravenous bolus of calcium gluconate and intravenous infusion of sodium chloride with insulin, glucose with insulin and sodium bicarbonte. After the treatment, all laboratory findings normalised together and the patient felt better. This case shows that physicians should be very careful when prescribing NSAIDs to elderly patients treated with drugs that affect renal function.
Expert Rev Neurother. 2010 Jul;10(7):1175-200.
Maayan L, Correll CU.
Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Management of antipsychotic-related weight gain.
Despite variations across individuals and agents, antipsychotics are associated with clearly documented weight gain and adverse metabolic effects. Although increased appetite/caloric intake and various receptors, hormones and peptides have been implicated, biological mechanisms contributing to the increase in weight and glucose and lipid abnormalities with antipsychotics are largely unknown. This has hampered the creation of antipsychotics that are free of cardiometabolic effects, even in antipsychotic-naive/early-phase patients, as well as the development of strategies that can prevent or drastically diminish the adverse cardiometabolic effects. In general, three strategies can reduce the cardiometabolic risk of antipsychotics: switching to a less orexigenic/metabolically adverse antipsychotic; adjunctive behavioral treatments; and adjunctive pharmacologic interventions. However, each of these strategies has only been shown to be modestly effective. Among different behavioral interventions (N = 14, n = 746), group and individual treatment, dietary counseling and cognitive-behavioral therapy seem to be similarly effective. Among 15 different pharmacologic strategies (N = 35, n = 1629), only metformin, fenfluramine, sibutramine, topiramate and reboxetine were more effective than placebo, with the most evidence being available for metformin, and no head-to-head trials comparing individual pharmacologic interventions. However, even in the most successful trials the risk reduction was modest. Weight was not decreased to a pretreatment level, and despite superiority compared with placebo, weight gain still often occurred, particularly in antipsychotic-naive patients and when interventions were 'preventively' coinitiated with antipsychotics. Future research should focus on combining treatment modalities or agents and on exploring novel mechanism-based interventions.
Rev Saude Publica. 2010 Jun 25. pii: S0034-89102010005000021. [Epub ahead of print]
Pinto CD, Miranda ES, Emmerick IC, Costa ND, Castro CG.
Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
[Medicine prices and availability in the Brazilian Popular Pharmacy Program.] [Article in Portuguese]
OBJECTIVE: To analyze the performance of the Programa Farmácia Popular do Brasil (FPB - Brazilian Popular Pharmacy Program) in the public and private sectors, in terms of availability and cost of medicines for hypertension and diabetes. METHODS: The methodology developed by the World Health Organization, in partnership with the Health Action International, was used to compare medicines prices and availability. This study was performed in May 2007, in different sectors (public, private and the Program's government-managed [FPB-P] and private-sector-managed [FPB-E] categories), in 30 cities in Brazil. A total of four medicines were analyzed: captopril 25mg and hydrochlorothiazide 25mg for hypertension; and metformin 500mg and glibenclamide 5mg for diabetes. RESULTS: FPB-E showed greatest medicine availability, while the public sector the lowest. The percentage of availability of similar medicines was higher than that of generic medicines, both in the public sector and in the FPB-P. Comparison of prices among sectors showed a lower purchase price in the FPB-E, followed by the FPB-P. The FPB-E charged prices that were over 90% cheaper than those in the private sector. The number of working days required to obtain treatment for hypertension and diabetes were fewer in the FPB-E. CONCLUSIONS: The lower availability found in the public sector could be one of the reasons for the migration of users from the public sector to the FPB. The high prices in the private sector also contribute for this Program to be an alternative of medicine access in Brazil.
Indian J Pharm Sci. 2009 May;71(3):331-5.
Arayne MS, Sultana N, Zuberi MH, Siddiqui FA.
Department of Chemistry, University of Karachi, Karachi-75270, Pakistan.
Spectrophotometric Quantitation of Metformin in Bulk Drug and Pharmaceutical Formulations using Multivariate Technique.
A sensitive and accurate UV spectrophotometric method with multivariate calibration technique for the determination of metformin hydrochloride in bulk drug and different pharmaceutical formulations has been described. This technique is based on the use of the linear regression equations by using relationship between concentration and absorbance at five different wavelength. The results were treated statistically and were found highly accurate, precise and reproducible. The method is accurate, precise (% recovery 102.50+/-0.063, CV
Indian J Pharm Sci. 2009 May;71(3):318-20.
Kar M, Choudhury PK.
Department of Pharmaceutical Sciences, Mohan Lal Sukhadia University, Udaipur-313 001, India.
HPLC method for estimation of metformin hydrochloride in formulated microspheres and tablet dosage form.
A simple, accurate, economical and reproducible HPLC method has been developed for quantitative estimation of metformin hydrochloride from tablet dosage form and formulated microspheres. The developed HPLC method is a reverse phase chromatographic method using phenomenex C(18) column and acetonitrile:phosphate buffer (65:35) pH adjusted to 5.75 with o-phosphoric acid as mobile phase and glipizide as internal standard. The linearity was observed in concentration range of 0-25 mug/ml for metformin hydrochloride. Results of analysis were validated statistically and by recovery studies.
West Indian Med J. 2009 Nov;58(5):433-6.
Sohrabvand F, Shariat M, Haghollahi F, Bagheri B.
Tehran University of Medical Sciences, Vali-e-Asr Reproductive Health Research Center, Iman Khomeini Hospital Complex, Tehran University of Medical Sciences, Keshavarz Boulevard, Tehran 14194 Iran. fsohrabvand@yahoo.com
Effect of metformin on miscarriage in pregnant patients with polycystic ovary syndrome.
BACKGROUND: This study was performed with the aim of evaluating the effect of metformin in reducing miscarriage when continued until the end of the first trimester of pregnancy in patients with polycystic ovary syndrome (PCOS) and infertility. SUBJECTS AND METHOD: From January 2004 to December 2005, a total of 75 pregnant women with PCOS were studied in three different groups. In Group A, metformin administration (500 mg three times daily (TDS)) was stopped immediately after diagnosis of pregnancy (5-6 weeks gestation), in Group B, metformin was administered until the end of 8 weeks gestation and in Group C until the end of 12 weeks gestation. The results of this study were then assessed using chi-square McNemar's, ANOVA Kruskal Wallis and logistic regression tests. RESULTS: There was a significant statistical difference between previous and current miscarriage in the current pregnancy with a decline in Group B from 40% to 8% and in group C from 32% to 4%. In spite of the reduced rate of miscarriage seen in Group A, from 20% to 4%, this difference was not statistically significant. Fetal anomalies were absent in all three groups. CONCLUSION: According to the current findings, it seems that continuing metformin during the first trimester of pregnancy has beneficial effects in patients with PCOS.
Equine Vet J. 2009 Dec;41(9):924-9.
Durham AE, Hughes KJ, Cottle HJ, Rendle DI, Boston RC.
The Liphook Equine Hospital, Forest Mere, Liphook, Hampshire GU30 7JG, UK.
Type 2 diabetes mellitus with pancreatic beta cell dysfunction in 3 horses confirmed with minimal model analysis.
REASONS FOR PERFORMING STUDY: Type 2 diabetes mellitus (T2DM) is diagnosed rarely in equine practice although it may be under-recognised. A greater awareness of the condition and therapeutic considerations would be to the benefit of such cases presenting in practice. More investigation into the pharmacological management of these cases is needed. OBJECTIVES: Three cases of diabetes mellitus were investigated using a specific test for insulin sensitivity and pancreatic beta cell function in order to define accurately and characterise the existence of T2DM in all 3 subjects. METHODS: The insulin-modified frequently sampled i.v. glucose tolerance test was performed in each case and the data so obtained were subject to minimal model analysis of insulin-glucose dynamics. Cases were then monitored following treatment using a combination of dietary modification, metformin, glibenclamide and pergolide. RESULTS: Marked insulin resistance was identified in each case and, furthermore, severe pancreatic beta cell dysfunction was present therefore classifying each case as end stage T2DM. Treatment was nevertheless associated with restoration of normoglycaemia in all cases. CONCLUSIONS: T2DM in horses may be more common than generally considered.In some cases individuals may respond to therapy aimed at restoring insulin sensitivity and pancreatic function. Drugs used in other species for the treatment of T2DM have not yet been adequately tested in horses. POTENTIAL RELEVANCE: T2DM should be considered as an important differential diagnosis in mature to elderly horses and ponies suffering from weight loss, polydipsia and polyuria. Clinicians should be encouraged to offer treatment and management advice when such cases are encountered.
Drug Class Reviews.
Norris SL, Carson S, Thakurta S, Chan BKS.
Portland (OR): Oregon Health & Science University; 2008.
Drug Class Review: Thiazolidinediones: Final Report Update 1 [Internet].
There are 2 thiazolidinediones approved for prescription use in the United States, rosiglitazone maleate (Avandia™) and pioglitazone hydrochloride (Actos®). Both drugs are approved by the United States Food and Drug Administration for use in adults for the treatment of type 2 diabetes, either as monotherapy or in combination with insulin, metformin, or sulfonylurea when diet, exercise, and a single agent does not result in adequate glycemic control. Neither drug is currently approved for use in prediabetes or the metabolic syndrome. The objective of this review was to compare thiazolidinediones in the treatment of type 2 diabetes, prediabetes, and the metabolic syndrome.
West J Emerg Med. 2008 Aug;9(3):160-4.
Suchard JR, Grotsky TA.
Department of Emergency Medicine, University of California, Irvine School of Medicine.
Fatal metformin overdose presenting with progressive hyperglycemia.
A 29-year-old man with no history of diabetes ingested over 60 grams of metformin in a suicide attempt. He presented to the emergency department with acute renal insufficiency, severe lactic acidosis, and rapidly-progressive hyperglycemia. The patient's peak serum glucose level of 707 mg/dL is the highest yet reported in a case of metformin toxicity. Treatment included sodium bicarbonate infusion and hemodialysis, but the patient suffered several cardiac arrests with pulseless electrical activity and ultimately expired 25 hours after the ingestion.
J Indian Med Assoc. 2008 Oct;106(10):643-4, 646-8.
Chaudhury K, Chaudhury S, Chowdhury S.
Department of Obstetrics and Gynaecology, Chittaranjan Seva Sadan, Kolkata.
Does metformin augment the ovulation inducing effects of clomiphene in non-obese women with polycystic ovary syndrome?
To decide if metformin augments clomiphene response for ovulation induction in non-obese women with polycystic ovary syndrome, a prospective randomised placebo-controlled trial was undertaken among 27 patients, who were found eligible for this study following clinical assessment and basic investigations. Women with polycystic ovary syndrome, even when non-obese, has increased insulin-resistance and do not respond favourably when treated with clomiphene for ovulation induction. The hypothesis is that by improving insulin- resistance and thus reversing from hyperinsulinaemia towards normal insulin secretion will enhance the responsiveness of these women to ovulation inducing effects of clomiphene. In the metformin group there were 15 patients who were given metformin 500mg orally 8 hourly daily for initial 3 months whereas in the placebo group there were 12 patients who were given folic acid (as placebo) 5mg orally once daily for initial 3 months. Thereafter, all the 27 patients in both groups were treated with clomiphene 50mg orally once daily from day 2 for 5 days in each month for subsequent 3 months. However, metformin and folic acid was continued in the metformin group and placebo group respectively for these subsequent 3 months when these patients were being treated with clomiphene for ovulation induction. Ovulation, as the outcome measure, was assessed by serial transvaginal ultrasound scanning from day 8/ day 9 and serum progesterone estimation on the 7th or 8th day following the ultrasound evidence of ovulation. Ovulation is taken to have occurred when serum progesterone was > or =8 ng/ml. Ovulation was noted to have occurred in 71.11% of the 45 cycles studied in 15 patients in the metformin group whereas ovulation occurred in 11.11% of the 36 cycles studied in 12 patients in the placebo group. This difference was highly statistically significant (p < 0.001) by Fisher's exact test. It can be conducted that metformin augments the ovulation inducing effects of clomiphene in non-obese women with polycystic ovary syndrome.
Nig Q J Hosp Med. 2008 Oct-Dec;18(4):211-5.
Adeneye AA.
Department of Pharmacology, Faculty of Basic Medical Sciences, Lagos State University College of Medicine, PMB 21266, Ikeja, Lagos, Nigeria. adenye2001@yahoo.com
Hypoglycemic and hypolipidemic effects of methanol seed extract of Citrus paradisi Macfad (Rutaceae) in alloxan-induced diabetic Wistar rats.
BACKGROUND: Alcohol decoction of Citrus paradisi Macfad (Rutaceae) seed is reputed for the local management of array of human diseases including, anemia, diabetes mellitus and obesity by some Yoruba herbalists (SouthWest, Nigeria). Despite its historic use, scientific evaluation of its folkloric use in the management of diabetes mellitus is scarce. OBJECTIVES: The present study was designed at investigating the glucose and lipid lowering effects of methanol seed extract of Citrus paradisi Macfad (MECP) in alloxan-induced diabetic rats. In addition, the phytochemical analysis of the extract was also conducted using standard procedures. METHODS: Young adult, male, alloxan-induced diabetic rats were randomly divided into groups I - VI with 12 rats in each group. Group I rats were the normal untreated rats while group II rats served as the diabetic untreated rats while Rats in groups III - VI served as diabetic rats treated with 100, 300 and 600 mg/kg/day MECP and 20 mg/kg/ day metformin, respectively, for 30 days. On the 15th and respectively, 31st day, blood samples from the fasted rats were obtained for fasting plasma glucose (FPG), plasma triglycerides (TG), total cholesterol (TC), high density lipoprotein- cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c) and very low density lipoprotein-cholesterol (VLDL-c) from the sacrificed rats. RESULTS: Oral treatment with 100 - 600 mg/kg/day MECP, for 30 days, resulted in significant (p < 0.05, p < 0.01, p < 0.001) reductions in FPG, TG, TC, LDL-c, VLDL-c in the diabetic rats, effects which were comparable to that of metformin. The extract also caused significant (p < 0.05, p < 0.01) rise in HDL-c values in the alloxan diabetic rats. Phytochemical result showed the presence of alkaloids, flavonoids, cardiac glycosides, tannins and saponin in varying concentrations. The biological effects recorded for the extract could be due to any or a combination of these phytochemical constituents. CONCLUSION: Results of this study lend support to the traditional use of grapefruit seeds in the management of type 1 diabetic patients and may suggest a role in orthodox management of the disease.
Drug Class Reviews.
McDonagh M, Peterson K, Thakurta SG, Dana T.
Portland (OR): Oregon Health & Science University; 2007.
Drug Class Review on Fixed Dose Combination Drug Products for the Treatment of Type 2 Diabetes and Hyperlipidemia: Final Report [Internet].
The combination of 2 drug entities in one dosage form is known as a fixed-dose combination product (FDCP). For the treatment of type 2 diabetes, there are 2 products that combine a sulfonylurea with metformin, 2 that combine metformin with a thiazolidinedione, 1 that combines metformin with a Dipeptidyl-Peptidase 4 (DPP-4) Inhibitor, and 2 that combine a thiazolidinedione with a sulfonylurea. For treatment of hyperlipidemia, 2 FDCPs are available: Vytorin and Advicor. Advicor is a combination of an HMG-CoA Reductase Inhibitor (statin) - lovastatin with an extended release formulation of niacin, while Vytorin is a combination of another statin, simvastatin, and a newer drug ezetimibe. Although the individual components of the FDCPs in this report have been shown to improve health outcomes, we believe it is still important to show whether outcomes are the same under the conditions of the FDCP where it is suggested that adherence and convenience are improved but dose adjustments are more difficult. The purpose of this review is to determine whether the purported advantages of taking 1 pill rather than 2 to treat hyperlipidemia and type 2 diabetes outweigh the potential disadvantages of not being able to adjust the doses of the two drugs separately.
Journ Annu Diabetol Hotel Dieu. 2007:13-20.
Holman R.
Diabetes Trial Unit, OCDEM, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, United Kingdom.
Metformin as first choice in oral diabetes treatment: the UKPDS experience.
Metformin has been used successfully since the 1950s as first line pharmacotherapy to treat people with type 2 diabetes. It is a biguanide that decreases blood glucose concentration by mechanisms different from those of insulin secretagogues, such as sulphonylureas, or exogenous insulin therapy. Metformin lowers, rather than increases, fasting plasma insulin concentrations and acts by enhancing insulin sensitivity, inducing greater peripheral uptake of glucose, and decreasing hepatic glucose output. By reducing hepatic glucose output it lowers blood glucose and insulin levels with minimal risk of hypoglycaemia, and when used as monotherapy can lower HbAlc by around 1.5%. It is usually well tolerated, the most common side effects being gastrointestinal. Of particular value is that the improved glucose control seen with metformin is achieved without weight gain. Concerns that it may increase the risk of lactic acidosis have largely been allayed with recent studies suggesting less than one case per 100,000 treated patients. The UK Prospective Diabetes Study (UKPDS) demonstrated a substantial beneficial effect of metformin therapy on cardiovascular disease (CVD) outcomes, with a 36% relative risk reduction in all cause mortality and a 39% relative risk reduction in myocardial infarction . The first ever joint ADA (American Diabetes Association) and EASD (European Association for the Study of Diabetes) consensus guidelines on the management of hyperglycaemia in type 2 diabetes state explicitly that metformin should be used as first-line foundation therapy, in addition to lifestyle interventions.
Med J Malaysia. 2007 Oct;62(4):294-8.
Dinesh KU, Subish P, Pranaya M, Shankar PR, Anil SK, Durga B.
Department of Hospital and Clinical Pharmacy/Pharmacology, Manipal Teaching Hospital / Manipal College of Medical Sciences, Pokhara, Nepal. dinesh17dec@rediffmail.com
Pattern of potential drug-drug interactions in diabetic out-patients in a tertiary care teaching hospital in Nepal.
A prospective study was conducted at Manipal Teaching Hospital, Pokhara, Nepal to identify and analyze the pattern of the potential DDIs (drug-drug interaction) in diabetes patients. A total of 182 patients who were prescribed 685 drugs (average, 3.76 drugs per prescription) were enrolled. Patients 51 to 60 years of age had a higher risk [43 patients, or (23.6%)] of developing DDIs. It was found that 174 (92.1%) of the potential DDIs were of "moderate" severity. Cardiovascular drugs carried a risk of DDIs (187 drugs, or 49.5%). The most common potential DDI observed was between metformin and enalapril (n = 64).
Arch Intern Med. 2006 Oct 9;166(18):1975-9.
Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM.
Departments of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Sha Tin.
Risk factors of vitamin B12 deficiency in patients receiving metformin.
The current study results indicate an increased risk of vitamin B(12) deficiency associated with current dose and duration of metformin use despite adjustment for many potential confounders. The risk factors identified have implications for planning screening or prevention strategies in metformin-treated patients.
BACKGROUND: Identification of risk factors for metformin-related vitamin B(12) deficiency has major potential implications regarding the management of diabetes mellitus. METHODS: We conducted a nested case-control study from a database in which the source population consisted of subjects who had levels of both serum vitamin B(12) and hemoglobin A(1c) checked in a central laboratory. We identified 155 cases of diabetes mellitus and vitamin B(12) deficiency secondary to metformin treatment. Another 310 controls were selected from the cohort who did not have vitamin B(12) deficiency while taking metformin. RESULTS: A total of 155 patients with metformin-related vitamin B(12) deficiency (mean +/- SD serum vitamin B(12) concentration, 148.6 +/- 40.4 pg/mL [110 +/- 30 pmol/L]) were compared with 310 matched controls (466.1 +/- 330.4 pg/mL [344 +/- 244 pmol/L]). After adjusting for confounders, we found clinically important and statistically significant association of vitamin B(12) deficiency with dose and duration of metformin use. Each 1-g/d metformin dose increment conferred an odds ratio of 2.88 (95% confidence interval, 2.15-3.87) for developing vitamin B(12) deficiency (P<.001). Among those using metformin for 3 years or more, the adjusted odds ratio was 2.39 (95% confidence interval, 1.46-3.91) (P = .001) compared with those receiving metformin for less than 3 years. After exclusion of 113 subjects with borderline vitamin B(12) concentration, dose of metformin remained the strongest independent predictor of vitamin B(12) deficiency. CONCLUSIONS: Our results indicate an increased risk of vitamin B(12) deficiency associated with current dose and duration of metformin use despite adjustment for many potential confounders. The risk factors identified have implications for planning screening or prevention strategies in metformin-treated patients.
An Med Interna. 2004 Jun;21(6):288-90.
Solano Remirez M, Gonzalez Arencibia C, Alvarez Frias M, Llorente Diaz B, Echegaray Agara M.
Servicio de Medicina Interna. Hospital de Navarra. Pamplona, Spain.
Lactic acidosis in diabetic patient treated with metformin.
The current study explains a case of metabolic acidosis in a man, recently diagnosed with type 2 Diabetes Mellitus under treatment with metformin. The study resulted that in some patients, beneficial developed lactic acidosis, specially in those who have predisposing factors and/or those who require high doses.
We present a case of metabolic acidosis ina man, recently diagnosed with type 2 Diabetes Mellitus under treatment with metformin. Metformin (along with Fenformin and Butformin) is an oral antihyperglycemic agent belonging to the biguanide group employed in the treatment of non insulin dependent diabetes (NIDDM). Its main use is in associattion with other oral agents in obese diabetic patients with difficult metabolic control. In some of these patients, clearly beneficial developed lactic acidosis, specially in those who have predisposing factors (respiratry failure, liver disease or cardiovascular disease) and/or those who require high dosis. For this reason we describe itacute;s pharmacokinetics, therapeutic indications and its correct use in this type of diabetic patient.
Ann Intern Med. 2005 Mar 1;142(5):323-32.
Herman WH, Hoerger TJ, Brandle M, Hicks K, Sorensen S, Zhang P, Hamman RF, Ackermann RT, Engelgau MM, Ratner RE; Diabetes Prevention Program Research Group.
University of Michigan Health System, Ann Arbor, Michigan, USA.
The cost-effectiveness of lifestyle modification or metformin in preventing type 2 diabetes in adults with impaired glucose tolerance.
The current study is to estimate the lifetime cost-utility of the Diabetes Prevention Program (DPP) interventions. The study suggested that cost-effectiveness improved when the interventions were implemented as they might be in routine clinical practice. the metformin intervention and did not represent good use of resources for persons older than 65 years of age.
BACKGROUND: The Diabetes Prevention Program (DPP) demonstrated that interventions can delay or prevent the development of type 2 diabetes. OBJECTIVE: To estimate the lifetime cost-utility of the DPP interventions. DESIGN: Markov simulation model to estimate progression of disease, costs, and quality of life. DATA SOURCES: The DPP and published reports. TARGET POPULATION: Members of the DPP cohort 25 years of age or older with impaired glucose tolerance. TIME HORIZON: Lifetime. PERSPECTIVES: Health system and societal. INTERVENTIONS: Intensive lifestyle, metformin, and placebo interventions as implemented in the DPP. OUTCOME MEASURES: Cumulative incidence of diabetes, microvascular and neuropathic complications, cardiovascular complications, survival, direct medical and direct nonmedical costs, quality-adjusted life-years (QALYs), and cost per QALY. RESULTS OF BASE-CASE ANALYSIS: Compared with the placebo intervention, the lifestyle and metformin interventions were estimated to delay the development of type 2 diabetes by 11 and 3 years, respectively, and to reduce the absolute incidence of diabetes by 20% and 8%, respectively. The cumulative incidence of microvascular, neuropathic, and cardiovascular complications were reduced and survival was improved by 0.5 and 0.2 years. Compared with the placebo intervention, the cost per QALY was approximately 1100 dollars for the lifestyle intervention and $31 300 for the metformin intervention. From a societal perspective, the interventions cost approximately 8800 dollars and 29,900 dollars per QALY, respectively. From both perspectives, the lifestyle intervention dominated the metformin intervention. RESULTS OF SENSITIVITY ANALYSIS: Cost-effectiveness improved when the interventions were implemented as they might be in routine clinical practice. The lifestyle intervention was cost-effective in all age groups. The metformin intervention did not represent good use of resources for persons older than 65 years of age. LIMITATIONS: Simulation results depend on the accuracy of the underlying assumptions, including participant adherence. CONCLUSIONS: Health policy should promote diabetes prevention in high-risk individuals.
Obstet Gynecol Surv. 2005 Mar;60(3):178-9
Baillargeon JP, Jakubowicz DJ, Iuomo MJ, Jakubowicz S, Nestler JE.
Hospital de Clinicas Caracas, Caracas, Venezuela; and the Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia.
Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity.
In the given study using 100 women the investigators concluded that insulin-sensitizing drugs are effective in nonobese women with polycystic ovary syndrome (PCOS) even if baseline insulin sensitivity is normal.
The goal of this randomized, controlled, double-blind trial was to learn whether insulin-sensitizing drugs can improve ovulation frequency and serum-free testosterone (T) in nonobese women with polycystic ovary syndrome (PCOS) whose insulin sensitivity was normal. The 100 women enrolled in the study, 17 to 40 years of age, had normal glucose tolerance, fasting insulin, and peak insulin levels during oral glucose tolerance testing (OGTT). The fasting glucose-to-insulin ratio also was normal. Criteria for PCOS were 8 or fewer menstrual periods in the past year and a serum total T exceeding 70 ng/dL. Participants received 850 mg metformin, 4 mg rosiglitazone, a combination of both treatments, or at least 1 placebo twice a day for 6 months. Treatment began when the women were in the equivalent of the follicular phase of the cycle.Only women given rosiglitazone gained significant body weight (1.1 kg), and the posttreatment body mass index was significantly greater in this group. All actively treated women had a significant decline in their waist-to-hip ratio. Systolic blood pressure fell significantly in all actively treated groups but not in placebo recipients. Diastolic pressure decreased and was similar in all groups at the end of the study. Ovulatory cycles were 6- to 8-fold more frequent with treatment and were highest in women given metformin or combination therapy. Ovulation rates at 6 months were markedly increased except in the placebo group. Menstrual bleeding also was greater in treated women. Combination treatment did not yield additive results for either ovulation or menstrual bleeding. Serum total and free T levels decreased significantly with active treatment. Compared with placebo, fasting insulin levels, the area under the insulin curve during an OGTT, and the OGTT-based insulin sensitivity index improved significantly after metformin or combination therapy, but not after rosiglitazone.The investigators concluded that insulin-sensitizing drugs are effective in nonobese women with PCOS even if baseline insulin sensitivity is normal.
Metabolism. 2005 Mar;54(3):314-20.
Jung HS, Youn BS, Cho YM, Yu KY, Park HJ, Shin CS, Kim SY, Lee HK, Park KS.
The effects of rosiglitazone and metformin on the plasma concentrations of resistin in patients with type 2 diabetes mellitus.
In the following study scientists examined the effects of rosiglitazone and metformin on the plasma resistin levels in individuals with type 2 diabetes mellitus. The study results suggested that the observed changes in the study in plasma resistin levels are not the consequences of improved insulin resistance, nor are they consequences of glycemic control. Considering the potential role of resistin in insulin resistance, decrease in resistin levels may contribute to improving insulin action with rosiglitazone treatment.
Abstract Resistin is a protein secreted from adipose tissue that is thought to play a role in insulin sensitivity. We examined the effects of rosiglitazone and metformin on the plasma resistin levels in individuals with type 2 diabetes mellitus. Patients with type 2 diabetes mellitus who showed poor glycemic control with glimepiride (4 mg/d) were randomized to rosiglitazone (4 mg/d) and metformin (500 mg bid) treatment groups. All subjects continued glimepiride treatment as well. The plasma concentrations of resistin were measured at baseline and at 6 months of treatment for both groups. The anthropometric parameters, fasting plasma glucose, HbA1c, total cholesterol, triglyceride, high-density lipoprotein cholesterol, free fatty acids, and adiponectin concentrations were also measured. After 6 months of treatment, the reduction in plasma glucose levels was similar between the 2 groups. There were no significant changes in the lipid profiles of either group during the study period. The plasma resistin levels decreased in the rosiglitazone group (2.49 +/- 1.93 vs 1.95 +/- 1.59 ng/ml; P < .05) but increased in the metformin group (2.61 +/- 1.69 vs 5.13 +/- 2.81 ng/ml; P < .05). The plasma adiponectin concentrations were increased in the rosiglitazone group (2.91 +/- 1.46 vs 4.23 +/- 1.77 mu g/ml; P < .05) but were unchanged in the metformin group. In summary, rosiglitazone treatment decreased the plasma resistin levels whereas metformin treatment increased them in patients with type 2 diabetes mellitus showing poor glycemic control with sulfonylurea therapy. These results suggest that the observed changes in plasma resistin levels are not the consequences of improved insulin resistance, nor are they consequences of glycemic control. Considering the potential role of resistin in insulin resistance, decrease in resistin levels may contribute to improving insulin action with rosiglitazone treatment.
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 Metformin scientific update
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