***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: Patients with type 2 diabetes mellitus ( T2DM ) with a glycated haemoglobin ( HbA1c ) level ≥7 and ≤10 % were r and omized to receive empagliflozin 12.5 mg twice daily ( n = 219 ) , 25 mg once daily ( n = 218 ) , 5 mg twice daily ( n = 219 ) or 10 mg once daily ( n = 220 ) , or placebo ( n = 107 ) as add‐on to stable‐dose metformin immediate release ( IR ) twice daily for 16 weeks . The primary endpoint was change from baseline in HbA1c at week 16 . At week 16 , change from baseline in HbA1c  with empagliflozin twice daily was non‐inferior to empagliflozin once daily and vice versa . The adjusted mean ( 95 % confidence interval ) difference in change from baseline in HbA1c with empagliflozin 12.5 mg twice daily versus 25 mg once daily was −0.11 % ( −0.26 , 0.03 ) , and with empagliflozin 5 mg twice daily versus 10 mg once daily it was −0.02 % ( −0.16 , 0.13 ) . All empagliflozin regimens were well tolerated ; thus , when used as add‐on to metformin IR in patients with T2DM , the therapeutic effect of empagliflozin twice‐daily and once‐daily regimens can be considered equivalent Background and Purpose — In the EMPA-REG OUTCOME trial ( Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients ) , empagliflozin added to st and ard of care in patients with type 2 diabetes mellitus and high cardiovascular risk reduced the risk of 3-point major adverse cardiovascular events , driven by a reduction in cardiovascular mortality , with no significant difference between empagliflozin and placebo in risk of myocardial infa rct ion or stroke . In a modified intent-to-treat analysis , the hazard ratio for stroke was 1.18 ( 95 % confidence interval , 0.89–1.56 ; P=0.26 ) . We further investigated cerebrovascular events . Methods — Patients were r and omized to empagliflozin 10 mg , empagliflozin 25 mg , or placebo ; 7020 patients were treated . Median observation time was 3.1 years . Results — The numeric difference in stroke  between empagliflozin and placebo in the modified intent-to-treat analysis was primarily because of 18 patients in the empagliflozin group with a first event > 90 days after last intake of study drug ( versus 3 on placebo ) . In a sensitivity analysis based on events during treatment or ⩽90 days after last dose of drug , the hazard ratio for stroke with empagliflozin versus placebo was 1.08 ( 95 % confidence interval , 0.81–1.45 ; P=0.60 ) . There were no differences in risk of recurrent , fatal , or disabling strokes , or transient ischemic attack , with empagliflozin versus placebo . Patients with the largest increases in hematocrit or largest decreases in systolic blood pressure did not have an increased risk of stroke . Conclusions — In patients with type 2 diabetes mellitus and high cardiovascular risk , there was no significant difference in the risk of cerebrovascular events with empagliflozin versus placebo . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01131676 OBJECTIVE To investigate the efficacy , safety , and tolerability of empagliflozin in patients with type 2 diabetes and hypertension . RESEARCH DESIGN AND METHODS Patients ( N = 825 ) with type 2 diabetes and hypertension ( mean seated systolic blood pressure [ SBP ] 130–159 mmHg and diastolic blood pressure [ DBP ] 80–99 mmHg ) were r and omized ( double blind ) to 10 mg or 25 mg empagliflozin or placebo once daily for 12 weeks . RESULTS At week 12 , adjusted mean difference versus placebo in change from baseline in mean 24-h SBP ( ambulatory blood pressure monitoring [ ABPM ] ) was −3.44 mmHg ( 95 % CI −4.78 , −2.09 ) with 10 mg empagliflozin and −4.16 mmHg ( −5.50 , −2.83 ) with 25 mg empagliflozin ( both P < 0.001 ) . At week 12 , adjusted mean difference versus placebo in change from baseline in mean 24-h DBP ( ABPM ) was −1.36 mmHg ( 95 % CI −2.15 , −0.56 ) with 10 mg empagliflozin and −1.72 mmHg ( 95 % CI −2.51 , −0.93 ) with 25 mg empagliflozin ( both P < 0.001 ) . Changes in office BP were consistent with ABPM . Adjusted mean difference versus placebo in change from baseline in HbA1c at week 12 was −0.62 % ( 95 % CI −0.72 , −0.52 ) ( −6.8 mmol/mol [ 95 % CI −7.9 , −5.7 ] ) with 10 mg empagliflozin and −0.65 % ( 95 % CI −0.75 , −0.55 ) ( −7.1 mmol/mol [ 95 % CI −8.2 , −6.0 ] ) with 25 mg empagliflozin ( both P < 0.001 )  . Empagliflozin was well tolerated . One patient on placebo and one patient on 10 mg empagliflozin reported events consistent with volume depletion . CONCLUSIONS Empagliflozin was associated with significant and clinical ly meaningful reductions in BP and HbA1c versus placebo and was well tolerated in patients with type 2 diabetes and hypertension Background This study evaluated the effect of empagliflozin on postpr and ial glucose ( PPG ) and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Methods Patients ( N = 60 ; baseline mean [ SD ] HbA1c 7.91 [0.80]% ; body mass index 24.3 [ 3.2 ] kg/m2 ) were r and omized to receive empagliflozin 10 mg ( n = 20 ) , empagliflozin 25 mg ( n = 19 ) or placebo ( n = 21 ) once daily as monotherapy for 28 days . A meal tolerance test and continuous glucose monitoring ( CGM ) for 24 hours were performed at baseline and on days 1 and 28 . The primary endpoint was change from baseline in area under the glucose concentration-time curve 3 hours after breakfast ( AUC1–4h for PPG ) at day 28 . Results Adjusted mean ( 95 % ) differences versus placebo in changes from baseline in AUC1 - 4h for PPG at day 1 were −97.1 ( −126.5 , −67.8 ) mg · h/dl with empagliflozin 10 mg and −91.6 ( −120.4 , −62.8 ) mg · h/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) and at day 28 were −85.5 ( −126.0 , −45.0 ) mg · h/dl with empagliflozin 10 mg and −104.9 ( −144.8 , −65.0 ) mg · h/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) . Adjusted mean ( 95 % CI ) differences versus placebo in change from baseline in 24-hour mean glucose ( CGM ) at day 1 were −20.8 ( −27.0 , −14.7 ) mg/dl with empagliflozin 10 mg and −23.9 ( −30.0 , −17.9 ) mg/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) and at day 28 were −24.5 ( −35.4 , −13.6 ) mg/dl with empagliflozin 10 mg and −31.7 ( −42.5,-20.9 ) mg/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) . Changes from baseline in mean amplitude of glucose excursions ( MAGE ; CGM ) were not significantly different with either empagliflozin dose versus placebo at either timepoint . Curves of mean glucose ( CGM ) did not change between baseline and day 1 or 28 with placebo , but shifted downward with empagliflozin . Percentage of time with glucose ≥70 to < 180 mg/dl increased from 52.0 % at baseline to 77.0 % at day 28 with empagliflozin 10 mg and from 55.0 % to 81.1 % with empagliflozin 25 mg , without increasing time spent with hypoglycemia . Conclusion Empagliflozin for 28 days reduced PPG from the first day and improved daily blood glucose control in Japanese patients with T2DM.Trial registration Clinical trials.gov 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 OBJECTIVE To investigate the efficacy and tolerability of empagliflozin as add-on to metformin and sulfonylurea in patients with type 2 diabetes . RESEAR 
    Output:
    
In conclusion  , empagliflozin  reduces systolic and diastolic blood pressure , uric acid , hemoglobin A1c , fasting plasma glucose , and body weight .
These data suggest the beneficial effects of empagliflozin on these cardiovascular risk factors in patients with type 2 diabetes mellitus