***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 the efficacy and safety of dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin and sulfonylurea . RESEARCH DESIGN AND METHODS Patients with HbA1c of 7.0 % ( 53 mmol/mol ) to 10.5 % ( 91 mmol/mol ) receiving sulfonylurea and metformin  were r and omized to receive dapagliflozin 10 mg/day ( n = 109 ) or placebo ( n = 109 ) for 24 weeks . RESULTS HbA1c ( baseline : dapagliflozin 8.08 % [ 65 mmol/mol ] ; placebo 8.24 % [ 67 mmol/mol ] ) and fasting plasma glucose ( baseline : dapagliflozin 167.4 mg/dL [ 9.29 mmol/L ] ; placebo 180.5 mg/dL [ 10.02 mmol/L ] ) significantly improved from baseline with dapagliflozin ( placebo-subtracted change –0.69 % [ –7.5 mmol/mol ] , P < 0.0001 ; –33.5 mg/dL [ –1.86 mmol/L ] , P < 0.0001 , respectively ) . More patients achieved a therapeutic glycemic response ( HbA1c < 7.0 % [ 53 mmol/mol ] ) with dapagliflozin ( 31.8 % ) versus placebo ( 11.1 % ) ( P < 0.0001 ) . Body weight and systolic blood pressure were significantly reduced from baseline over 24 and 8 weeks , respectively , with dapagliflozin ( placebo-subtracted change –2.1 kg , P < 0.0001 ; –3.8 mmHg , P = 0.0250 ) . Patients receiving dapagliflozin showed placebo-subtracted increases in total , LDL , and HDL cholesterol ( 11.4 mg/dL , P = 0.0091 ; 11.4 mg/dL , P = 0.0030 ; 2.2 mg/dL , P = 0.0172 , respectively ) with no change in LDL/HDL cholesterol ratio ( 0.1 ; P = 0.2008 ) or triglycerides ( –16.5 mg/dL ; P = 0.1755 ) . Adverse events occurred in 48.6 % of patients receiving dapagliflozin and 51.4 % receiving placebo . Significantly more patients with dapagliflozin compared with placebo experienced hypoglycemia ( 12.8 vs. 3.7 % ; P = 0.024 ) and genital infections ( 5.5 vs. 0 % ; P = 0.029 ) . Events of urinary tract infection were reported by 6.4 % of patients in both groups . CONCLUSIONS Dapagliflozin was well tolerated and effective over 24 weeks as add-on to metformin plus sulfonylurea . Adverse effects included hypoglycemia and genital infections OBJECTIVE This study compared the efficacy and safety of initial combinations of empagliflozin + metformin with empagliflozin and metformin monotherapy in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS The study r and omized 1,364 drug-naïve patients ( HbA1c > 7.5 to ≤12 % [ > 58 to ≤108 mmol/mol ] ) for 24 weeks to empagliflozin 12.5 mg b.i.d . + metformin 1,000 mg b.i.d . , empagliflozin 12.5 mg b.i.d . + metformin 500 mg b.i.d . , empagliflozin 5 mg b.i.d + metformin 1,000 mg b.i.d . , empagliflozin 5 mg b.i.d . + metformin 500 mg b.i.d . , empagliflozin 25 mg q.d . , empagliflozin 10 mg q.d . , metformin 1,000 mg b.i.d . , or metformin 500 mg b.i.d . The primary end point was change from baseline in HbA1c at week 24 . RESULTS At week 24 , reductions in HbA1c ( mean baseline 8.6–8.9 % [ 70–73 mmol/mol ] ) were −1.9 to −2.1 % with empagliflozin + metformin twice-daily regimens , −1.4 % with both empagliflozin once-daily regimens , and −1.2 to −1.8 % with metformin twice-daily regimens . Reductions in HbA1c were significantly greater with empagliflozin + metformin twice-daily regimens than with empagliflozin once-daily regimens ( P < 0.001 ) and with metformin twice-daily regimens ( P < 0.01 ) . Reductions in weight at week 24 were significantly greater with empagliflozin + metformin twice-daily regimens ( range −2.8 to −3.8 kg ) than with metformin twice-daily regimens ( −0.5 to −1.3 kg ) ( P < 0.001 for all ) . Adverse event ( AE ) rates were similar across groups ( 56.7–66.3 % ) . No hypoglycemic AEs required assistance . CONCLUSIONS Initial combinations of empagliflozin + metformin for 24 weeks significantly reduced HbA1c versus empagliflozin once daily and metformin twice daily , without increased hypoglycemia , reduced weight versus metformin twice daily , and were well tolerated OBJECTIVE To evaluate the efficacy and safety of combinations of empagliflozin/linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin . RESEARCH DESIGN AND METHODS Subjects were r and omized to a combination of empagliflozin 25 mg/linagliptin 5 mg ( n = 137 ) , empagliflozin 10 mg/linagliptin 5 mg ( n = 136 ) , empagliflozin 25 mg ( n = 141 ) , empagliflozin 10 mg ( n = 140 ) , or linagliptin 5 mg ( n = 132 ) as add-on to metformin for 52 weeks . The primary end point was change from baseline in HbA1c at week 24 . RESULTS At week 24 , reductions in HbA1c ( mean baseline 7.90–8.02 % [ 62.8–64.1 mmol/mol ] ) with empagliflozin/linagliptin were superior to those with empagliflozin or linagliptin alone as add-on to metformin ; adjusted mean ( SE ) changes from baseline were −1.19 % ( 0.06 ) ( −13.1 mmol/mol [ 0.7 ] ) with empagliflozin 25 mg/linagliptin 5 mg , −1.08 % ( 0.06 ) ( −11.8 mmol/mol [ 0.7 ] ) with empagliflozin 10 mg/linagliptin 5 mg , −0.62 % ( 0.06 ) ( −6.8 mmol/mol [ 0.7 ] ) with empagliflozin 25 mg , −0.66 % ( 0.06 ) ( −7.2 mmol/mol [ 0.7 ] ) with empagliflozin 10 mg , and −0.70 % ( 0.06 ) ( −7.6 mmol/mol [ 0.7 ] ) with linagliptin 5 mg ( P < 0.001 for all comparisons ) . In these groups , respectively , 61.8 , 57.8 , 32.6 , 28.0 , and 36.1 % of subjects with baseline HbA1c ≥7 % ( ≥53 mmol/mol ) had HbA1c < 7 % ( < 53 mmol/mol ) at week 24 . Efficacy was maintained at week 52 . The proportion of subjects with adverse events ( AEs ) over 52 weeks was similar across treatment arms ( 68.6–73.0 % ) , with no hypoglycemic AEs requiring assistance . CONCLUSIONS Combinations of empagliflozin/linagliptin as second-line therapy for 52 weeks significantly reduced HbA1c compared with the individual components and were well tolerated 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 
    Output:
    
When compared with placebo , empagliflozin and canagliflozin  improved all three endpoints , whereas dapagliflozin  improved worsening HF .
When compared with other SGLT2i , empagliflozin was superior for all-cause and cardiovascular mortality reduction .
Empagliflozin , canagliflozin and dapagliflozin had similar effects on improving worsening HF .
Ertugliflozin had no effect on any of the three endpoints investigated .
Empagliflozin and canagliflozin  improved survival with empagliflozin being superior to the other SGLT2i .
Empagliflozin , canagliflozin and dapagliflozin had similar effects on improving worsening HF .