***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: CONTEXT Dapagliflozin , a selective sodium-glucose cotransporter 2 ( SGLT2 ) inhibitor , reduces hyperglycemia in patients with type 2 diabetes mellitus ( T2DM ) by increasing urinary glucose excretion , and weight loss is a consistent associated finding . OBJECTIVES Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components . DESIGN AND SETTING This was a 24-wk , international , multicenter , r and omized , parallel-group , double-blind , placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries . PATIENTS Included were 182 patients with T2DM ( mean values : women 63.3 and men 58.6 yr of age ; hemoglobin A1c 7.17 % , body mass index 31.9 kg/m2 , and body weight 91.5 kg ) inadequately controlled on metformin . INTERVENTION Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk . MAIN OUTCOME MEASURES Primary endpoint was total body weight ( TBW ) change from baseline at wk 24 . Key secondary endpoints were waist circumference and dual-energy x-ray absorptiometry total-body fat mass ( FM ) changes from baseline at wk 24 , and patient proportion achieving body weight reduction of at least 5 % at wk 24 . In a subset of patients , magnetic resonance assessment of visceral adipose tissue ( VAT ) and sc adipose tissue ( SAT ) volume and hepatic lipid content were also evaluated . RESULTS At wk 24 , placebo-corrected changes with dapagliflozin were as follows : TBW , -2.08 kg [ 95 % confidence interval (CI)=-2.84 to -1.31 ; P<0.0001 ] ; waist circumference , -1.52 cm ( 95 % CI=-2.74 to -0.31 ; P=0.0143 ) ; FM , -1.48 kg ( 95 % CI=-2.22 to -0.74 ; P=0.0001 ) ; proportion of patients achieving weight reduction of at least 5 % , + 26.2 % ( 95 % CI=15.5 to 36.7 ; P<0.0001 ) ; VAT , -258.4 cm3 ( 95 % CI=-448.1 to -68.6 ; nominal P=0.0084 ) ; SAT , -184.9 cm3 ( 95 % CI=-359.7 to -10.1 ; nominal P=0.0385 ) . In the dapagliflozin vs. placebo groups , respectively , serious adverse events were reported in 6.6 vs. 1.1 % ; events suggestive of vulvovaginitis , balanitis , and related genital infection in 3.3 vs. 0 % ; and lower urinary tract infections in 6.6 vs. 2.2 % . CONCLUSIONS Dapagliflozin reduces TBW , predominantly by reducing FM , VAT and SAT in T2DM inadequately controlled with metformin OBJECTIVE Dapagliflozin , a highly selective inhibitor of the renal sodium-glucose cotransporter-2 , increases urinary excretion of glucose and lowers plasma glucose levels in an insulin-independent manner . We evaluated the efficacy and safety of dapagliflozin in treatment-naive patients with type 2 diabetes . RESEARCH DESIGN AND METHODS This was a 24-week parallel-group , double-blind , placebo-controlled phase 3 trial . Patients with A1C 7.0–10 % ( n = 485 ) were r and omly assigned to one of seven arms to receive once-daily placebo or 2.5 , 5 , or 10 mg dapagliflozin once daily in the morning ( main cohort ) or evening ( exploratory cohort ) . Patients with A1C 10.1–12 % ( high-A1C exploratory cohort ; n = 73 ) were r and omly assigned 1:1 to receive blinded treatment with a morning dose of 5 or 10 mg/day dapagliflozin . The primary end point was change from baseline in A1C in the main cohort , statistically tested using an ANCOVA . RESULTS In the main cohort , mean A1C changes from baseline at week 24 were −0.23 % with placebo and −0.58 , −0.77 ( P = 0.0005 vs. placebo ) , and −0.89 % ( P < 0.0001 vs. placebo ) with 2.5 , 5 , and 10 mg dapagliflozin , respectively . Signs , symptoms , and other reports suggestive of urinary tract infections and genital infection were more frequently noted in the dapagliflozin arms . There were no major episodes of hypoglycemia . Data from exploratory cohorts were consistent with these results . CONCLUSIONS Dapagliflozin  lowered hyperglycemia in treatment-naive patients with newly diagnosed type 2 diabetes . The near absence of hypoglycemia and an insulin-independent mechanism of action make dapagliflozin a unique addition to existing treatment options for type 2 diabetes OBJECTIVE To examine the safety and efficacy of dapagliflozin , a sodium-glucose cotransporter-2 inhibitor , added on to pioglitazone in type 2 diabetes inadequately controlled on pioglitazone . RESEARCH DESIGN AND METHODS Treatment-naive patients or those receiving metformin , sulfonylurea , or thiazolidinedione  entered a 10-week pioglitazone dose-optimization period with only pioglitazone . They were then r and omized , along with patients previously receiving pioglitazone ≥30 mg , to 48 weeks of double-blind dapagliflozin 5 ( n = 141 ) or 10 mg ( n = 140 ) or placebo  ( n = 139 ) every day plus open-label pioglitazone . The primary objective compared HbA1c change from baseline with dapagliflozin plus pioglitazone versus placebo plus pioglitazone at week 24 . Primary analysis was based on ANCOVA model using last observation carried forward ; all remaining analyses used repeated- measures analysis . RESULTS At week 24 , the mean reduction from baseline in HbA1c was −0.42 % for placebo versus −0.82 and −0.97 % for dapagliflozin 5 and 10 mg groups , respectively ( P = 0.0007 and P < 0.0001 versus placebo ) . Patients receiving pioglitazone alone  had greater weight gain ( 3 kg ) than those receiving dapagliflozin plus pioglitazone ( 0.7–1.4 kg ) at week 48 . Through 48 weeks : hypoglycemia was rare ; more events suggestive of genital infection were reported with dapagliflozin ( 8.6–9.2 % ) than placebo ( 2.9 % ) ; events suggestive of urinary tract infection showed no clear drug effect ( 5.0–8.5 % for dapagliflozin and 7.9 % for placebo ) ; dapagliflozin plus pioglitazone groups had less edema ( 2.1–4.3 % ) compared with placebo plus pioglitazone ( 6.5 % ) ; and congestive heart failure and fractures were rare . CONCLUSIONS In patients with type 2 diabetes inadequately controlled on pioglitazone  , the addition of dapagliflozin further reduced HbA1c levels and mitigated the pioglitazone-related weight gain without increasing hypoglycemia risk Background Despite the number of medications for type 2 diabetes , many people with the condition do not achieve good glycaemic control . Some existing glucose-lowering agents have adverse effects such as weight gain or hypoglycaemia . Type 2 diabetes tends to be a progressive disease , and most patients require treatment with combinations of glucose-lowering agents . The sodium glucose co-transporter 2 ( SGLT2 ) receptor inhibitors are a new class of glucose-lowering agents . Objective To assess the clinical effectiveness and safety of the SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes . Data sources MEDLINE , Embase , Cochrane Library ( all sections ) ; Science Citation Index ; trial registries ; conference abstract s ; drug regulatory authorities ; bibliographies of retrieved papers . Inclusion criteria R and omised controlled trials of SGLT2 receptor inhibitors compared with placebo or active comparator in type 2 diabetes in dual or combination therapy . Methods Systematic review . Quality assessment used the Cochrane risk of bias score . Results Seven trials , published in full , assessed dapagliflozin and one assessed canagliflozin . Trial quality appeared good . Dapagliflozin 10 mg reduced HbA1c by −0.54 % ( weighted mean differences ( WMD ) , 95 % CI −0.67 to −0.40 ) compared to placebo , but there was no difference compared to glipizide . Canagliflozin  reduced HbA1c slightly more than sitagliptin ( up to −0.21 % vs sitagliptin ) . Both dapagliflozin and canagliflozin  led to weight loss  ( dapagliflozin WMD −1.81 kg ( 95 % CI −2.04 to −1.57 ) , canagliflozin up to −2.3 kg compared to placebo ) . Limitations Long-term trial extensions suggested that effects were maintained over time . Data on canagliflozin are currently available from only one paper . Costs of the drugs are not known so cost-effectiveness can not be assessed . More data on safety are needed , with the Food and Drug Administration having concerns about breast and bladder cancers . Conclusions Dapagliflozin appears effective in reducing HbA1c and weight in type 2 diabetes , although more safety data are needed OBJECTIVE This study evaluated the ability of the incretin mimetic exenatide ( exendin-4 ) to improve glycemic control in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy . RESEARCH DESIGN AND METHODS This was a triple-blind , placebo-controlled , 30-week study conducted at 101 sites in the U.S. After a 4-week , single-blind , placebo lead-in period , 377 subjects were r and omized ( 60 % men , age 55 + /- 11 years , BMI 33 + /- 6 kg/m(2 ) , HbA(1c ) 8.6 + /- 1.2 % [ + /-SD ] ) and began 4 weeks at 5 microg subcutaneous exenatide twice daily ( before breakfast and dinner ; arms A and B ) or placebo . Subsequently , subjects in arm B were escalated to 10 microg b.i.d . exenatide . All subjects continued sulfonylurea therapy . RESULTS At week 30 , HbA(1c ) changes from baseline were -0.86 + /- 0.11 , -0.46 + /- 0.12 , and 0.12 + /- 0.09 % ( + /-SE ) in the 10-microg , 5-microg , and placebo arms , respectively ( adjusted P < 0.001 ) . Of evaluable subjects with baseline HbA(1c ) > 7 % ( n = 237 ) , 41 % ( 10 microg ) , 33 % ( 5 microg ) , and 9 % ( placebo ) achieved HbA(1c ) < or= 7 % ( P < 0.001 ) . Fasting plasma glucose concentrations decreased in the 10-microg arm compared with placebo ( P < 0.05 ) . Subjects in the exenatide arms had dose-dependent progressive weight loss , with an end-of- study loss in the 10-microg exenatide arm of -1.6 + /- 0.3 kg from baseline ( P < 0.05 vs. placebo ) . The most frequent adverse events were generally mild or moderate and gastrointestinal in nature . No severe hypoglycemia was observed . CONCLUSIONS Exenatide significantly reduced HbA(1c ) in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea . Exenatide was generally well tolerated and was associated with weight loss BACKGROUND Improved blood-glucose control decreases the progression of diabetic microvascular disease , but the effect on macrovascular complications is unknown . There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation . We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a r and omised controlled trial . METHODS 3867 newly diagnosed patients with type 2 diabetes , median age 54 years ( IQR 48 - 60 
    Output:
    
Based on fixed-effect NMA , all treatment classes result ed in statistically significant decreases in HbA1c at follow-up compared to placebo .
Conclusions Dapagliflozin , DPP-4 inhibitors and GLP-1 analogues , in combination with SU , all provided better short-term glycaemic control compared to SU monotherapy .
Dapagliflozin was the only add-on therapy that had both a favourable weight and hypoglycaemia profile compared to the other classes of treatment evaluated