***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 effects of canagliflozin , a sodium-glucose cotransporter 2 inhibitor , in type 2 diabetes mellitus inadequately controlled with metformin monotherapy . RESEARCH DESIGN AND METHODS This was a double-blind , placebo-controlled , parallel-group , multicenter , dose-ranging study in 451 subjects r and omized to canagliflozin 50 , 100 , 200 , or 300 mg once daily ( QD ) or 300 mg twice daily ( BID ) , sitagliptin 100 mg QD , or placebo . Primary end point was change in A1C from baseline through week 12 . Secondary end points included change in fasting plasma glucose ( FPG ) , body weight , and overnight urinary glucose-to-creatinine ratio . Safety and tolerability were also assessed . RESULTS Canagliflozin was associated with significant reductions in A1C from baseline ( 7.6–8.0 % ) to week 12 : −0.79 , −0.76 , −0.70 , −0.92 , and −0.95 % for canagliflozin 50 , 100 , 200 , 300 mg QD and 300 mg BID , respectively , versus −0.22 % for placebo ( all P < 0.001 ) and −0.74 % for sitagliptin . FPG was reduced by −16 to −27 mg/dL , and body weight was reduced by −2.3 to −3.4 % , with significant increases in urinary glucose-to-creatinine ratio . Adverse events were transient , mild to moderate , and balanced across arms except for a non – dose-dependent increase in symptomatic genital infections with canagliflozin ( 3–8 % ) versus placebo and sitagliptin ( 2 % ) . Urinary tract infections were reported without dose dependency in 3–9 % of canagliflozin , 6 % of placebo , and 2 % of sitagliptin  arms . Overall incidence of hypoglycemia was low . CONCLUSIONS Canagliflozin added onto metformin significantly improved glycemic control in type 2 diabetes and was associated with low incidence of hypoglycemia and significant weight loss . The safety/tolerability profile of canagliflozin was favorable except for increased frequency of genital infections in females 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 We investigated the efficacy and safety of the sodium glucose cotransporter 2 inhibitor , empagliflozin , added to multiple daily injections of insulin ( MDI insulin ) in obese patients with type 2 diabetes mellitus ( T2DM ) . RESEARCH DESIGN AND METHODS Patients inadequately controlled on MDI insulin ± metformin ( mean HbA1c 8.3 % [ 67 mmol/mol ] ; BMI 34.8 kg/m2 ; insulin dose 92 international units/day ) were r and omized and treated with once-daily  empagliflozin 10 mg ( n = 186 ) , empagliflozin 25 mg ( n = 189 ) , or placebo  ( n = 188 ) for 52 weeks . Insulin dose was to remain stable in weeks 1–18 , adjusted to meet glucose targets in weeks 19–40 , then stable in weeks 41–52 . The primary end point was change from baseline in HbA1c at week 18 . Secondary end points were changes from baseline in insulin dose , weight , and HbA1c at week 52 . RESULTS Adjusted mean ± SE changes from baseline in HbA1c were −0.50 ± 0.05 % ( −5.5 ± 0.5 mmol/mol ) for placebo versus −0.94 ± 0.05 % ( −10.3 ± 0.5 mmol/mol ) and −1.02 ± 0.05 % ( −11.1 ± 0.5 mmol/mol ) for empagliflozin 10 mg and empagliflozin 25 mg , respectively , at week 18 ( both P < 0.001 ) . At week 52 , further reductions with insulin titration result ed in changes from baseline in HbA1c of −0.81 ± 0.08 % ( −8.9 ± 0.9 mmol/mol ) , −1.18 ± 0.08 % ( −12.9 ± 0.9 mmol/mol ) , and −1.27 ± 0.08 % ( −13.9 ± 0.9 mmol/mol ) with placebo , empagliflozin 10 mg , and empagliflozin 25 mg , respectively , and final HbA1c of 7.5 % ( 58 mmol/mol ) , 7.2 % ( 55 mmol/mol ) , and 7.1 % ( 54 mmol/mol ) , respectively . More patients attained HbA1c < 7 % ( < 53 mmol/mol ) with empagliflozin ( 31–42 % ) versus placebo ( 21 % ; both P < 0.01 ) . Empagliflozin 10 mg and empagliflozin 25 mg reduced insulin doses ( −9 to −11 international units/day ) and weight ( −2.4 to −2.5 kg ) versus placebo ( all P < 0.01 ) at week 52 . CONCLUSIONS In obese , difficult-to-treat patients with T2DM inadequately controlled on high MDI insulin doses  , empagliflozin  improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements AIMS Dapagliflozin , a highly selective inhibitor of sodium-glucose cotransporter 2 ( SGLT2 ) , reduces hyperglycaemia and weight in patients with type 2 diabetes mellitus ( T2DM ) by increasing urinary glucose excretion . Long-term glycaemic control , body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment . METHODS This r and omized , double-blind , placebo-controlled study ( NCT00855166 ) enrolled patients with T2DM [ mean : age 60.7 years ; HbA1c 7.2 % ; body mass index ( BMI ) 31.9 kg/m(2 ) ; body weight 91.5 kg ] inadequately controlled on metformin . Patients ( N = 182 ) were r and omly assigned 1 : 1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period . At week 102 , changes from baseline in HbA1c , weight , waist circumference , total body fat mass as measured by dual-energy X-ray absorptiometry ( DXA ) , serum markers of bone turnover , bone mineral density ( BMD ) as measured by DXA , and adverse events were evaluated . RESULTS A total of 140 patients ( 76.9 % ) completed the study . Over 102 weeks , dapagliflozin-treated patients showed reductions in HbA1c by -0.3 % , weight by -4.54 kg , waist circumference by -5.0 cm and fat mass by -2.80 kg without increase in rate of hypoglycaemia . Compared with placebo , no meaningful changes from baseline in markers of bone turnover or BMD were identified over 102 weeks . One fracture occurred in each treatment group . The frequency of urinary tract infection ( UTI ) and genital infection was similar in both treatment groups . CONCLUSIONS Over 102 weeks , dapagliflozin improved glycaemic control , and reduced weight and fat mass , without affecting markers of bone turnover or BMD in patients with T2DM inadequately controlled on metformin AIMS Dapagliflozin , a selective inhibitor of sodium-glucose cotransporter 2 ( SGLT2 ) , has been shown to improve glycaemic control , stabilize insulin dosing and mitigate insulin-associated weight gain over 48 weeks in patients whose type 2 diabetes mellitus ( T2DM ) was inadequately controlled despite high doses of insulin . Here the efficacy and safety of dapagliflozin therapy after a total of 104 weeks are evaluated in this population . METHODS This was a 24-week , r and omized , placebo-controlled , double-blinded , multicentre trial followed by two site- and patient-blinded extension periods of 24 and 56 weeks ( NCT00673231 ) , respectively . A total of 808 patients , whose T2DM was inadequately controlled on insulin ≥30 IU/day , with or without up to two oral antidiabetic drugs  , were r and omly assigned to receive placebo or 2.5 , 5 or 10 mg/day of dapagliflozin for 104 weeks . At 48 weeks , patients on dapagliflozin 5 mg were switched to 10 mg . Outcomes over 104 weeks included change from baseline in HbA1c , insulin dose and body weight ; analyses used observed cases and included data after insulin up-titration . Adverse events ( AEs ) were evaluated throughout 104 weeks . RESULTS Five hundred and thirteen patients ( 63.6 % ) completed the study . Mean HbA1c changes from baseline at 104 weeks were -0.4 % in the placebo group and -0.6 to -0.8 % in the dapagliflozin groups . In the placebo group , mean insulin dose increased by 18.3 IU/day and weight increased by 1.8 kg at 104 weeks , whereas in the dapagliflozin groups 
    Output:
    
They noticed an increase in the chance of UTI in the SGLT2i groups compared to the control groups on placebo or other oral antidiabetic agents .
This increased chance was found predominantly with the use of Dapagliflozin , Canagliflozin , and Tofogliflozin , regardless of the dosing .