***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The effects of metformin therapy on whole body and splanchnic amino acid turnover are not known . Therefore , we have studied fasting and postpr and ial phenylalanine kinetics in type 2 diabetic subjects ( non-insulin-dependent diabetes mellitus ) , previously treated with diet only , both before and after 4 weeks of either metformin ( 850 mg twice a day ) ( n = 11 ) or placebo administration ( n = 6 ) .  Phenylalanine kinetic was evaluated by means of a multiple isotope technique : tritiated phenylalanine was infused i.v . , whereas carbon-labeled phenylalanine was incorporated into a chemically-defined meal . Compared with placebo , metformin administration decreased both fasting ( from 162 + /- 17 to 141 + /- 20 mg/dl ) and postpr and ial ( from 217 + /- 20 to 164 + /- 20 mg/dl ) glucose concentrations ( P < 0.05-P < 0.01 ) . Fasting insulin concentrations were unaffected , but postmeal insulin tended to be lower ( P < 0.06 ) after metformin . Compared with the pretreatment period , metformin administration did not change total phenylalanine rate of appearance ( fasted state , 0.74 + /- 0.10 vs. 0.71 + /- 0.08 mumol/kg.min ; fed state , 0.77 + /- 0.10 vs. 0.75 + /- 0.08 mumol/kg.min , respectively ) , dietary and endogenous phenylalanine rate of appearance , dietary phenylalanine oxidation , and splanchnic uptake , similar to what was observed in the placebo group . Our data indicate that , at least after a 4-week treatment , metformin does not affect fasting and postpr and ial protein turnover , as indicated by phenylalanine data , in subjects with mild non-insulin-dependent diabetes mellitus OBJECTIVE This study was undertaken to assess the effects of combined treatment with insulin and metformin in patients with type 2 diabetes mellitus in whom dietary measures , weight control , and oral antihyperglycemic therapy had failed . BACKGROUND Insulin resistance in peripheral tissues , increased hepatic gluconeogenesis , and impaired insulin secretion are the underlying factors in the development of type 2 diabetes . Metformin is a biguanide antihyperglycemic agent that increases peripheral insulin sensitivity , reduces hepatic gluconeogenesis , and decreases intestinal glucose absorption . METHODS Thirty-one patients ( 24 women , 7 men ; mean age , 61.8 years ; mean body mass index [ BMI ] , 28.0 kg/m2 ) were enrolled in this r and omized , double-blind , 2-way , crossover , placebo-controlled study . Patients with type 2 diabetes who were treated previously with insulin or oral hypoglycemic agents and who had a glycosylated hemoglobin ( HbA1c ) level > 9 % or a fasting blood glucose level > 8 mmol/L were included . Patients who were being treated with oral agents were switched to insulin therapy and required to maintain stable blood glucose control for 2 months prior to r and omization . Patients received insulin plus either metformin 1,700 mg/d or placebo for 5 months , followed by a 2-month washout period , and were then crossed over to the other treatment arm for 5 months of additional treatment ( total treatment period : 12 months ) . RESULTS Thirty patients completed the study ; 1 patient withdrew early because of hypoglycemia . Compared with placebo , metformin produced significant reductions from overall baseline in mean daily insulin dose requirement ( -8.69 units ( 17.2 % ] , P < 0.001 ) , HbA1c level ( -0.74 [ 9.9 % ] , P = 0.005 ) , serum fructosamine level ( -44.40 micromol/L , P = 0.026 ) , 24-hour blood glucose profile ( P = 0.008 ) , and total cholesterol level ( -0.42 mmol/L , P = 0.005 ) . No treatment effects were observed on body weight , blood pressure , serum high-density lipoprotein cholesterol levels , or serum triglyceride levels . There was no correlation between BMI and reduction in HbA1C . No major side effects were reported . CONCLUSIONS Combination therapy with metformin and insulin improves glycemic control and reduces insulin requirements . with no major side effects , in patients with type 2 diabetes and may improve the risk profile in this patient population OBJECTIVE To evaluate whether simultaneous initial treatment of both insulin resistance and impaired beta-cell insulin secretion with glyburide/metformin tablets is superior to monotherapy with each component agent . RESEARCH DESIGN AND METHODS In this r and omized , parallel-group , placebo-controlled , multicentre study , 806 patients with type 2 diabetes ( mean duration , 3 years ) who had failed diet and exercise were r and omly assigned to 4 weeks of therapy with placebo , glyburide 2.5 mg , metformin 500 mg , glyburide/metformin 1.25/250 mg , or glyburide/metformin 2.5/500 mg once daily . Doses were then titrated over 8 weeks based on glycaemic response . The primary outcome measure was change from baseline in mean HbA1c after 20 weeks . Changes in fasting plasma glucose , lipids and body weight were also assessed along with 2-h postpr and ial glucose and insulin values after a st and ardized meal . RESULTS At week 20 , patients taking glyburide/metformin 1.25/250 mg or 2.5/500 mg tablets had greater reductions in HbA1c levels ( -1.48 % and -1.53 % respectively ) compared with placebo ( -0.21 % ; both p < 0.001 ) , glyburide ( -1.24 % ; p = 0.016 and p = 0.004 respectively ) or metformin ( -1.03 % ; both p < 0.001 ) . Fasting plasma glucose concentrations were reduced more in both glyburide/metformin groups compared with placebo and metformin ( p < 0.001 ) ; patients in both combination therapy groups also had significantly lower postpr and ial glucose concentrations compared with placebo , glyburide and metformin . CONCLUSIONS Initial combination treatment with glyburide/metformin tablets produces greater improvements in glycaemic control than either glyburide or metformin monotherapy . The superiority of initial therapy with glyburide/metformin tablets may arise from simultaneous treatment of both pathophysiological defects of type 2 diabetes OBJECTIVE To compare the effects of bedtime NPH Insulin vs Metformin combined with Glibenclamide in patients who are obese and had secondary failure to sulphonylurea treatment . DESIGN AND METHODS Prospect i ve , r and omized , comparative study of patients having type-II diabetes , without complications with associated obesity and secondary failure to sulphonylureas . Thirty-six obese patients who continued to have blood glucose values of fasting > 150 mg/dl and /or r and om > 220 mg/dl , after 8 weeks of intensive dietary and drug therapy . INTERVENTIONS For the 20 weeks of study , the patients were r and omised in two equal groups , one receiving 20 to 40 units of NPH Insulin at bed time and the second group , Metformin upto a maximum dose of 3 grams , along with Sulphonylureas . RESULTS Both the groups showed , a significant reduction in the blood glucose values , with an average decrease of 50 mg/dl . The other monitored parameters , such as , serum cholesterol , triglycerides and blood pressure values , also demonstrated a similar downwards trend . However , the drop out rate was high in the Insulin treated group and the remainder group did show slight increase in weight and BMI , while the reverse , stood true , for the metformin group , with 100 % compliance rate . CONCLUSION Metformin , in obese , type II diabetics , with secondary failure to Sulphonylureas , is an effective , safe and well tolerated treatment , which not only improves the metabolic control but also favourably modifies other parameters such as weight , total cholesterol and triglyceride values OBJECTIVE Although some studies have suggested a direct action of troglitazone on vascular cells , its effects on diabetic vascular diseases have not been reported . We therefore investigated the effect of troglitazone on microalbuminuria in patients with incipient diabetic nephropathy . RESEARCH DESIGN AND METHODS A total of 30 patients with type 2 diabetes associated with microalbuminuria ( urinary albumin-to-creatinine ratio [ ACR ] [ milligrams per gram creatinine ] ranging from 30 to 300 mg/g creatinine ) were studied . They were r and omly divided into two groups : patients treated with metformin ( 500 mg/day , n = 13 ) or with troglitazone ( 400 mg/day , n = 17 ) for 12 weeks . ACR , lipid profile , blood pressure , glycated hemoglobin , and plasma glucose during meal-load tests  were measured every 4 weeks . RESULTS Anthropometric indices ( BMI and percent fat ) , lipid profile , and blood pressure did not change with either treatment . Fasting and postmeal glucose levels decreased similarly in the two groups . Decrements in glycated hemoglobin were greater in the metformin group at 4 and 8 weeks after the initiation of treatment ( P < 0.05 ) . Troglitazone reduced ACR ( median [ 25–75th percentiles ] ) from 70 ( 49–195 ) to 40 ( 31–90 ) mg/g creatinine at 4 weeks ( P = 0.021 ) and maintained these reduced levels throughout the treatment period ( 8 weeks : 35 [ 26–68 ] , P = 0.007 ; 12 weeks : 43 [ 26–103 ] , P = 0.047 ) . Metformin did not change ACR throughout the 12 weeks . CONCLUSIONS Troglitazone ameliorated microalbuminuria in diabetic nephropathy . Furthermore , our findings suggest that troglitazone has some effects on vascular cells other than lowering plasma glucose levels . Troglitazone might be useful for diabetic angiopathy , including nephropathy and coronary artery disease Coronary heart disease is a major cause of morbidity in NIDDM and is likely to be related to the abnormalities in serum lipids and lipoproteins commonly associated with it . The effects of treatment in general , and of oral hypoglycaemic drugs in particular , on serum lipids in NIDDM are not clear . In a cross-over study , the effects of 3 months treatment with metformin glibenclamide on body weight , blood glucose control , and serum lipoproteins were compared in 35 patients with NIDDM , inadequately controlled by diet alone .  Glibenclamide alone increased body weight .  Glibenclamide and metformin achieved equivalent blood glucose control , independent of initial body mass index . Neither drug affected serum triglyceride .  Metformin significantly reduced low density lipoprotein cholesterol ( mean change -0.34 mmol/1.95 % confidence intervals -0.12 to -0.57 mmol/l , p less than 0.01 ) . Neither drug altered high density lipoprotein or subfraction cholesterol . Changes in serum lipoproteins were also studied in 14 patients with NIDDM on long term metformin therapy , after 6 weeks placebo and again 6 weeks after restarting active drug therapy . Withdrawal of metformin result ed in a rise in fasting blood glucose , HbA1 , serum total and low density lipoprotein ( LDL ) cholesterol . Restarting the drug reversed these changes . Multivariate analysis showed that serum total and LDL cholesterol varied with treatment , but not with glycaemic control . Metformin can therefore lower total and LDL cholesterol in NIDDM and this effect appears to be maintained long term Type 2 diabetes affects over 150 million adults worldwide and this figure is expected to double over the next 25 yr . This increase will be accompanied by a marked increase in the number of patients with ESRD due to diabetes . We hypothesized that a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes We r and omly assigned 3234 nondiabetic persons with elevated fasting and postload plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 % weight loss and at least 150 min of physical activity per week . The mean age of the participants was 51 yr , and the mean body mass index was 34.0 kg/m(2 ) ; 68 % were women , and 45 % were members of non-Caucasian racial/ethnic groups . The average follow 
    Output:
    
Patients assigned to metformin monotherapy showed a significant benefit for glycaemia control , weight , dyslipidaemia , and diastolic blood pressure .
Metformin presents a strong benefit for HbA1c when compared with placebo and diet ; and a moderated benefit for : glycaemia control , LDL cholesterol , and BMI or weight when compared with sulphonylureas .
AUTHORS ' CONCLUSIONS Metformin may be the first therapeutic option in the diabetes mellitus type 2 with overweight or obesity , as it may prevent some vascular complications , and mortality .
Metformin produces beneficial changes in glycaemia control , and moderated in weight , lipids , insulinaemia and diastolic blood pressure .
Sulphonylureas , alpha-glucosidase inhibitors , thiazolidinediones , meglitinides , insulin , and diet fail to show more benefit for glycaemia control , body weight , or lipids , than metformin