***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 Aims We examined the efficacy , safety and tolerability of canagliflozin , a sodium glucose co-transporter 2 inhibitor , in Japanese patients with type 2 diabetes ( T2DM ) undergoing diet and exercise therapy . Methods Patients aged 20–80 years with T2DM diagnosed ≥3 months previously , and HbA1c of 6.9–9.9 % were r and omized to 50 , 100 , 200 or 300 mg canagliflozin or placebo once daily for 12 weeks . The primary and secondary endpoints were changes in HbA1c , fasting plasma glucose ( FPG ) , urinary glucose/creatinine and postpr and ial glycaemic parameters following a meal test . The safety assessment s included adverse events ( AEs ) and clinical laboratory tests . Results Overall , 383 patients were r and omized to receive either placebo ( n = 75 ) , or 50 mg ( n = 82 ) , 100 mg ( n = 74 ) , 200 mg ( n = 77 ) or 300 mg canagliflozin ( n = 75 ) . At week 12 , significant reductions in HbA1c were observed in all canagliflozin groups relative to placebo ( −0.61 , –0.80 , –0.79 and −0.88 % for 50 , 100 , 200 and 300 mg , respectively , versus + 0.11 % for placebo ; all , p < 0.01 ) . FPG and postpr and ial glycaemic parameters improved significantly in the canagliflozin  groups . Body weight was significantly decreased by canagliflozin . No deaths or drug-related serious AEs were reported . There was no dose-dependent increase in the incidence of AEs in the canagliflozin groups . The incidence of hypoglycaemia was low ; episodes were not severe or dose dependent . Canagliflozin did not affect serum creatinine levels or the urinary albumin/creatinine ratio . Conclusions Treatment with canagliflozin for 12 weeks significantly improved glycaemic control and reduced body weight in Japanese patients with T2DM . Canagliflozin was well tolerated Background Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus ( T2DM ) . The efficacy and safety of canagliflozin were evaluated in patients with T2DM < 65 and ≥65 years of age . Methods Pooled data from 4 r and omised , placebo-controlled , 26-week , Phase 3 studies ( N = 2,313 ) evaluating canagliflozin 100 and 300 mg were analysed by age : < 65 years ( n = 1,868 ; mean age , 52.8 years ) or ≥65 years ( n = 445 ; mean age , 69.3 years ) . Efficacy evaluations included change from baseline in glycaemic parameters and systolic blood pressure ( BP ) , and percent change from baseline in body weight . Assessment of safety/tolerability included adverse event ( AE ) reports , incidence of documented hypoglycaemia , and percent change from baseline in fasting plasma lipids . Results Canagliflozin 100 and 300 mg reduced HbA1c and fasting plasma glucose relative to placebo in patients < 65 and ≥65 years of age . Both canagliflozin doses reduced body weight and systolic BP relative to placebo in patients < 65 and ≥65 years of age . Incidence of overall AEs was similar across all treatment groups in patients < 65 and ≥65 years of age . Incidences of serious AEs and AE-related discontinuations were similar across all treatment groups in patients < 65 years of age and higher with canagliflozin 100 mg than other groups in patients ≥65 years of age . As in patients < 65 years of age , incidences of genital mycotic infections and osmotic diuresis-related AEs were higher with canagliflozin relative to placebo in those ≥65 years of age . Incidences of urinary tract infections ( UTIs ) , renal-related AEs , AEs related to volume depletion , and documented hypoglycaemia episodes were similar across all treatment groups in patients ≥65 years of age ; no notable trends were observed with canagliflozin 100 and 300 mg relative to placebo in these AEs among patients < 65 years of age . Changes in lipid parameters  with canagliflozin were similar in both age subsets . Conclusions Canagliflozin  improved glycaemic control , body weight , and systolic BP , and was generally well tolerated in older patients with T2DM.Trial registration Clinical Trials.gov , NCT01081834 ; NCT01106677 ; NCT01106625 ; NCT01106690 Aims /hypothesisThe aim of this work was to evaluate the efficacy and safety of canagliflozin vs placebo and sitagliptin in patients with type 2 diabetes who were being treated with background metformin . Methods This r and omised , double-blind , four-arm , parallel-group , Phase 3 study was conducted at 169 centres in 22 countries between April 2010 and August 2012 . Participants ( N = 1,284 ) with type 2 diabetes aged ≥18 and ≤80 years who had inadequate glycaemic control ( HbA1c ≥7.0 % [ 53 mmol/mol ] and ≤10.5 % [ 91 mmol/mol ] ) on metformin therapy received canagliflozin 100 mg or 300 mg , sitagliptin 100 mg , or placebo ( n = 368 , 367 , 366 , 183 , respectively ) for a 26 week , placebo- and active-controlled period followed by a 26 week , active-controlled period ( placebo group switched to sitagliptin [ placebo/sitagliptin ] ) and were included in the modified intent-to-treat analysis set . R and omisation was performed using a computer-generated schedule ; participants , study centres and the sponsor were blinded to group assignment . The primary endpoint was change from baseline in HbA1c at week 26 ; secondary endpoints included changes in HbA1c ( week 52 ) and fasting plasma glucose ( FPG ) , body weight , and systolic blood pressure ( BP ; weeks 26 and 52 ) . Adverse events ( AEs ) were recorded throughout the study . Results At week 26 , canagliflozin 100 mg and 300 mg reduced HbA1c vs placebo ( −0.79 % , –0.94 % , –0.17 % , respectively ; p < 0.001 ) . At week 52 , canagliflozin 100 mg and 300 mg demonstrated non-inferiority , and canagliflozin 300 mg demonstrated statistical  superiority , to sitagliptin in lowering HbA1c ( −0.73 % , –0.88%,–0.73 % , respectively ) ; differences ( 95 % CI ) vs sitagliptin were 0 % ( −0.12 , 0.12 ) and −0.15 % ( −0.27 , –0.03 ) , respectively . Canagliflozin 100 mg and 300 mg reduced body weight vs placebo ( week 26 : –3.7 % , –4.2 % , –1.2 % , respectively ; p < 0.001 ) and sitagliptin ( week 52 : –3.8 % , –4.2 % , –1.3 % , respectively ; p < 0.001 ) . Both canagliflozin doses reduced FPG and systolic BP vs placebo ( week 26 ) and sitagliptin ( week 52 ) ( p < 0.001 ) . Overall AE and AE-related discontinuation rates were generally similar across groups , but higher with canagliflozin 100 mg . Genital mycotic infection and osmotic diuresis-related AE rates were higher with canagliflozin ; few led to discontinuations . Hypoglycaemia incidence was higher with canagliflozin . Conclusions /interpretationCanagliflozin improved glycaemia and reduced body weight vs placebo ( week 26 ) and sitagliptin ( week 52 ) and was generally well tolerated in patients with type 2 diabetes on metformin . Clinical trial registry Clinical Trials.gov NCT01106677 Funding This study was supported by Janssen Research & Development , LLC Aim The efficacy and safety of canagliflozin , a sodium glucose co-transporter 2 inhibitor , was evaluated in patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled with metformin and pioglitazone . Methods In this r and omized , double-blind , phase 3 study , patients ( N = 342 ) received canagliflozin 100 or 300 mg during a 26-week , placebo-controlled , core period and a 26-week , active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg . Efficacy comparisons for canagliflozin versus placebo at week 26 are reported , with no comparisons versus sitagliptin at week 52 ( sitagliptin used to maintain double-blind and control for safety ) . Safety data are reported for canagliflozin and placebo/sitagliptin . Results Canagliflozin 100 and 300 mg significantly lowered haemoglobin A1c ( HbA1c ) compared with placebo at week 26 ( −0.89 % , −1.03 % and −0.26 % ; p < 0.001 ) ; reductions with canagliflozin 100 and 300 mg were maintained at week 52 ( −0.92 % and −1.03 % ) . Relative to placebo , both canagliflozin doses significantly reduced body weight ( −2.5 and −3.5 kg ) , fasting plasma glucose and systolic blood pressure ( BP ) at week 26 ( p < 0.05 for all ) , with reductions maintained at week 52 . Overall adverse event ( AE ) incidence over 52 weeks was 69.9 , 76.3 and 76.5 % with canagliflozin 100 and 300 mg and placebo/sitagliptin ; AE-related discontinuation and serious AE rates were low . Incidences of genital mycotic infections and AEs related to osmotic diuresis and volume depletion were higher with canagliflozin than placebo/sitagliptin . Conclusion Canagliflozin  
    Output:
    
Conclusion 300 mg canagliflozin was not associated with significantly higher adverse events compared to 100 mg canagliflozin in those patients who were treated for T2DM .