***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: 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 Study the effects of exenatide ( EXE ) plus rosiglitazone ( ROSI ) on β-cell function and insulin sensitivity using hyperglycemic and euglycemic insulin clamp techniques in participants with type 2 diabetes on metformin . RESEARCH DESIGN AND METHODS In this 20-week , r and omized , open-label , multicenter study , participants ( mean age , 56 ± 10 years ; weight , 93 ± 16 kg ; A1C , 7.8 ± 0.7 % ) continued their metformin regimen and received either EXE 10 μg b.i.d . ( n = 45 ) , ROSI 4 mg b.i.d . ( n = 45 ) , or EXE 10 μg b.i.d . + ROSI 4 mg b.i.d . ( n = 47 ) . Seventy-three participants underwent clamp procedures to quantitate insulin secretion and insulin sensitivity . RESULTS A1C declined in all groups ( P < 0.05 ) , but decreased most with EXE+ROSI ( EXE+ROSI , −1.3 ± 0.1 % ; ROSI , −1.0 ± 0.1 % , EXE , −0.9 ± 0.1 % ; EXE+ROSI vs. EXE or ROSI , P < 0.05 ) . ROSI result ed in weight gain , while EXE and EXE+ROSI  result ed in weight loss ( EXE , −2.8 ± 0.5 kg ; EXE+ROSI , −1.2 ± 0.5 kg ; ROSI , + 1.5 ± 0.5 kg ; P < 0.05 between and within all groups ) . At week 20 , 1st and 2nd phase insulin secretion was significantly higher in EXE and EXE+ROSI versus ROSI ( both P < 0.05 ) . Insulin sensitivity ( M value ) was significantly higher in EXE+ROSI versus EXE ( P = 0.014 ) . CONCLUSIONS Therapy with EXE+ROSI offset the weight gain observed with ROSI and elicited an additive effect on glycemic control with significant improvements in β-cell function and insulin sensitivity BACKGROUND Management of type 2 diabetes mellitus ( DM ) that involves uptitration of monotherapy to the maximum dose has been associated with delays in achieving glycemic control and an increased number of adverse events ( AEs ) . Studies have reported the benefits of adding a thiazolidinedione to metformin ( MET ) , but none has compared the effect of adding a thiazolidinedione to MET versus increasing the daily dose of MET to 3 g. OBJECTIVE The goal of this study was to investigate the benefits of fixed-dose combination rosiglitazone and MET ( RSG/MET ) compared with high-dose MET monotherapy in patients with type 2 DM . METHODS This was a 24-week , multicenter , r and omized , double-blind , parallel-group study . Patients previously treated with MET entered a 4-week , single-blind , run-in period with MET 2 g/d and were then r and omized to RSG/MET 4 mg/2 g per day or MET 2.5 g/d . At week 8 , medication was escalated to RSG/MET 8 mg/2 g per day or MET 3 g/d . The primary efficacy end point was change in glycosylated hemoglobin ( HbA1c ) at week 24 . Tolerability was assessed , including the frequency and severity of AEs . RESULTS A total of 568 patients comprised the safety population ( MET , 280 ; RSG/MET , 288 ) and 551 formed the intent-to-treat group ( MET , 272 ; RSG/MET , 279 ) . Baseline characteristics of the safety population were comparable in the 2 groups ; body mass index ( mean [ SD ] ) was 32.2 ( 4.8 ) kg/m(2 ) and 32.1 ( 4.9 ) kg/m(2 ) in the RSG/MET and MET groups , respectively . RSG/MET  reduced HbA(1c ) ( mean [ SD ] ) from 7.4 % ( 1.0 % ) to 7.1 % ( 1.1 % ) at week 24 , compared with a reduction from 7.5 % ( 1.0 % ) to 7.4 % ( 1.1 % ) with MET ( treatment difference , -0.22 % ; P = 0.001 ) . Fasting plasma glucose ( mean [ SD ] ) was reduced from 166.2 ( 29 ) to 144.1 ( 33 ) mg/dL with RSG/MET and from 169.3 ( 33 ) to 164.0 ( 37 ) mg/dL with MET ( treatment difference , -18.3 mg/dL ; P < 0.001 ) . In addition , 54 % of patients treated with RSG/MET achieved HbA(1c ) levels < 7.0 % , compared with 36 % with MET ( odds ratio , 2.42 ; P < 0.001 ) . RSG/MET increased homeostasis model assessment ( HOMA ) estimates of insulin sensitivity by 34.4 % versus 6.5 % with MET ( treatment difference , 24.8 % ; P < 0.001 ) . HOMA beta-cell function increased by 15.9 % with RSG/MET versus 2.5 % with MET ( treatment difference , 14.0 % ; P < 0.001 ) . RSG/MET decreased C-reactive protein by a mean of 39.4 % versus 16.0 % with MET ( treatment difference , -33.8 % ; P < 0.001 ) . RSG/MET was generally well tolerated , with the majority of AEs mild to moderate in nature . Serious AEs were reported in 3 % of patients receiving RSG/MET and 2 % with MET . Overall rates of gastrointestinal AEs were 23 % with RSG/MET and 26 % with MET ; however , there was an increased incidence of diarrhea ( 14 % vs 6 % ) and abdominal pain ( 9 % vs 6 % ) with MET . There was a mean ( SE ) increase in weight with RSG/MET ( 1.3 [ 0.22 ] kg ) and a mean decrease ( -0.9 [ 0.26 ] kg ) with MET . Patients receiving RSG/MET reported improvements in treatment satisfaction compared with MET . CONCLUSIONS In this study , the RSG/MET fixed-dose combination ( 8 mg/2 g per day ) was an effective and well-tolerated treatment for type 2 DM and enabled more patients to reach glycemic targets than high-dose MET ( 3 g/d ) Metformin and glibenclamide were compared in a r and omized , double-blind trial in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) using a parallel group design . The study was performed in primary health care , and the main purpose was to assess combination therapy with the two drugs as primary treatment versus conventional oral therapy . After a 2 months diet period patients were r and omized to commence treatment with either metformin , glibenclamide or the combination of both . Patients r and omized to monotherapy received the alternative drug in addition if the maximal dose i.e. 3 g metformin or 14 mg glibenclamide was insufficient to normalize the fasting blood glucose concentration ( FBG ) . R and omization and dose escalation occurred at FBG greater than or equal to 6.7 mmol/l . The titrated dose was continued for 6 months , whereafter placebo was given for 2 weeks . Seventy-two patients were r and omized to either the metformin group ( n = 38 ) or the glibenclamide group ( n = 34 ) . Fifty-six completed 6 months treatment , twenty-eight in each r and omized group . Glycaemic control was unchanged after diet alone in all groups . The improvement during drug treatment was highly significant ( p less than 0.001 ) , mean FBG difference ( + /- SEM ) 3.2 + /- 0.4 mmol/l and mean HbA1c difference ( + /- SEM ) 1.5 + /- 0.2 % ( n = 56 ) . There were no significant differences between patients treated solely with metformin ( n = 16 ) and glibenclamide ( n = 17 ) or between patients treated with a combination of glibenclamide added to metformin ( n = 12 ) and metformin added to glibenclamide ( n = 11 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Aims To compare glucose control over 18 months between rosiglitazone oral combination therapy and combination metformin and sulphonylurea in people with Type 2 diabetes . Methods RECORD , a multicentre , parallel-group study of cardiovascular outcomes , enrolled people with an HbA1c of 7.1–9.0 % on maximum doses of metformin or sulphonylurea .  If on metformin they were r and omized to add-on rosiglitazone or sulphonylurea ( open label ) and if on sulphonylurea to rosiglitazone or metformin . HbA1c was managed to ≤ 7.0 % by dose titration . A prospect ively defined analysis of  glycaemic control on the first 1122 participants is reported here , with a primary outcome assessed against a non-inferiority margin for HbA1c of 0.4 % . Results At 18 months , HbA1c reduction on background metformin was similar with rosiglitazone and sulphonylurea [ difference 0.07 ( 95 % CI −0.09 , 0.23)% ] , as was the change when rosiglitazone or metformin was added to sulphonylurea [ 0.06 ( −0.09 , 0.20)% ] . At 6 months , the effect on HbA1c was greater with add-on sulphonylurea , but was similar whether sulphonylurea was added to rosiglitazone or metformin  . Differences in fasting plasma glucose were not statistically significant at 18 months [ rosiglitazone vs. sulphonylurea −0.36 ( −0.74 , 0.02 ) mmol/l , rosiglitazone vs. metformin −0.34 ( −0.73 , 0.05 ) mmol/l ] . Increased homeostasis model assessment insulin sensitivity and reduced C-reactive protein were greater with rosiglitazone than metformin or sulphonylurea ( all P ≤ 0.001 ) . Body weight was significantly increased with rosiglitazone compared with sulphonylurea [ difference 1.2 ( 0.4 , 2.0 ) kg , P = 0.003 ] and metformin [ difference 4.3 ( 3.6 , 5.1 ) kg , P < 0.001 ] . Conclusions In people with diabetes  , rosiglitazone in combination with metformin or sulphonylurea was demonstrated to be non-inferior 
    Output:
    
A high strength of evidence showed that most medications were similarly efficacious at lowering hemoglobin A1c by about 1 absolute percentage point compared with baseline values .
The addition of most oral medications to initial monotherapy further improved glycemiccontrol by lowering A1c by another 1 percentage point .
The only exception was the DPP-4 inhibitor class , which did not lower A1c to the same extent as metformin when used as monotherapy .
Overall , metformin was found to have a more favorable effect on body weight when compared with other medications .
Two-drug combinations compared with each other demonstrated similar reductions in A1c levels .
Metformin decreased low-density lipoprotein cholesterol ( LDL-C ) relative to pioglitazone , sulfonylureas , and DPP-4 inhibitors .
Sulfonylureas had a 4-fold higher risk of mild-to-moderate hypoglycemia compared with metformin alone , and , in combination with metformin , had more than a 5-fold increased risk compared with metformin plus a thiazolidinedione .
Thiazolidinediones had an increased risk of congestive heart failure relative to sulfonylureas , and an increased risk for bone fractures relative to metformin .
Diarrhea occurred more often for metformin users compared with thiazolidinedione users .