***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 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 /hypothesisType 2 diabetes is difficult to manage in patients with a long history of disease requiring insulin therapy .  Moreover , addition of most currently available oral antidiabetic agents increases the risk of hypoglycaemia . Vildagliptin is a dipeptidyl peptidase-IV inhibitor , which improves glycaemic control by increasing pancreatic beta cell responsiveness to glucose and suppressing inappropriate glucagon secretion . This study assessed the efficacy and tolerability of vildagliptin added to insulin therapy in patients with type 2 diabetes . Material s and methods This was a multicentre , 24-week , double-blind , r and omised , placebo-controlled , parallel-group study in patients with type 2 diabetes that was inadequately controlled ( HbA1c = 7.5–11 % ) by insulin . Patients received vildagliptin ( n = 144 ; 50 mg twice daily ) or placebo ( n = 152 ) while continuing insulin therapy . Results Baseline HbA1c averaged 8.4 ± 0.1 % in both groups . The adjusted mean change from baseline to endpoint ( AMΔ ) in HbA1c was −0.5 ± 0.1 % and −0.2 ± 0.1 % in patients receiving vildagliptin or placebo , respectively , with a significant between-treatment difference ( p = 0.01 ) . In patients aged ≥65 years  , the AMΔ HbA1c was −0.7 ± 0.1 % in the vildagliptin group vs −0.1 ± 0.1 % in the placebo group ( p < 0.001 ) . The incidence of adverse events was similar in the vildagliptin ( 81.3 % ) and placebo ( 82.9 % ) groups . However , hypoglycaemic events were less common ( p < 0.001 ) and less severe ( p < 0.05 ) in patients receiving vildagliptin than in those receiving placebo . Conclusions /interpretationVildagliptin decreases HbA1c in patients whose type 2 diabetes is poorly controlled with high doses of insulin . Addition of vildagliptin to insulin therapy is also associated with reduced confirmed and severe hypoglycaemia . Clinical Trials.gov ID no. : NCT 00099931 Aims To investigate the efficacy and tolerability of empagliflozin added to basal insulin‐treated type 2 diabetes . Methods Patients inadequately controlled [ glycated haemoglobin ( HbA1c ) > 7 to ≤10 % ( > 53 to ≤86 mmol/mol ) ] on basal insulin ( glargine , detemir , NPH ) were r and omized to empagliflozin 10 mg ( n = 169 ) , empagliflozin 25 mg ( n = 155 ) or placebo ( n = 170 ) for 78 weeks . The baseline characteristics were balanced among the groups [ mean HbA1c 8.2 % ( 67 mmol/mol ) , BMI 32.2 kg/m2 ] . The basal insulin dose was to remain constant for 18 weeks , then could be adjusted at investigator 's discretion . The primary endpoint was change from baseline in HbA1c at week 18 . Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78 . Results At week 18 , the adjusted mean ± st and ard error changes from baseline in HbA1c were 0.0 ± 0.1 % ( −0.1 ± 0.8 mmol/mol ) for placebo , compared with −0.6 ± 0.1 % ( −6.2 ± 0.8 mmol/mol ) and −0.7 ± 0.1 % ( −7.8 ± 0.8 mmol/mol ) for empagliflozin 10 and 25 mg , respectively ( both p < 0.001 ) . At week 78 , empagliflozin 10 and 25 mg significantly reduced HbA1c , insulin dose and weight vs placebo ( all  p < 0.01 ) , and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo ( p = 0.004 ) . Similar percentages of patients had confirmed hypoglycaemia in all groups ( 35–36 % ) . Events consistent with urinary tract infection were reported in 9 , 15 and 12 % of patients on  placebo , empagliflozin 10 and 25 mg , and events consistent with genital infection were reported in 2 , 8 and 5 % , respectively .  Conclusions Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo OBJECTIVE To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes . METHODS After a 2 week placebo run-in period , eligible patients inadequately controlled on long-acting , intermediate-acting or premixed insulin ( HbA1c > or = 7.5 % and < or = 11 % ) , were r and omised 1:1 to the addition of once-daily sitagliptin 100 mg or matching placebo over a 24-week study period . The study capped the proportion of r and omised patients on insulin plus metformin at 75 % . Further , the study capped the proportion of r and omised patients on premixed insulin at 25 % . The metformin dose and the insulin dose were to remain stable throughout the study . The primary endpoint was HbA1c change from baseline at week 24 . RESULTS Mean baseline characteristics were similar between the  sitagliptin ( n = 322 ) and placebo ( n = 319 ) groups , including HbA1c ( 8.7 vs. 8.6 % ) , diabetes duration ( 13 vs. 12 years ) , body mass index ( 31.4 vs. 31.4 kg/m(2 ) ) , and total daily insulin dose ( 51 vs. 52 IU ) , respectively . At 24 weeks , the addition of sitagliptin significantly ( p < 0.001 ) reduced HbA1c by 0.6 % compared with placebo ( 0.0 % ) . A greater proportion of patients achieved an HbA1c level < 7 % while r and omised to sitagliptin as compared with placebo ( 13 vs. 5 % respectively ; p < 0.001 ) . Similar HbA1c reductions were observed in the patient strata defined by insulin type ( long-acting and intermediate-acting insulins or premixed insulins ) and by baseline metformin treatment . The addition of sitagliptin significantly ( p < 0.001 ) reduced fasting plasma glucose by 15.0 mg/dl ( 0.8 mmol/l ) and 2-h postmeal glucose by 36.1 mg/dl ( 2.0 mmol/l ) relative to placebo . A higher incidence of adverse experiences was reported with sitagliptin ( 52 % ) compared with placebo ( 43 % ) , due mainly to the increased incidence of hypoglycaemia ( sitagliptin , 16 % vs. placebo , 8 % ) . The number of hypoglycaemic events meeting the protocol -specified criteria for severity was low with sitagliptin ( n = 2 ) and placebo ( n = 1 ) . No significant change from baseline in body weight was observed in either group . CONCLUSION In this 24-week study , the addition of sitagliptin to ongoing , stable-dose insulin therapy with or without concomitant metformin improved glycaemic control and was generally well tolerated in patients with type 2 diabetes OBJECTIVE To evaluate the efficacy and long-term safety of linagliptin added to basal insulins in type 2 diabetes inadequately controlled on basal insulin with or without oral agents . RESEARCH DESIGN AND METHODS A total of 1,261 patients ( HbA1c ≥7.0 % [ 53 mmol/mol ] to ≤10.0 % [ 86 mmol/mol ] ) on basal insulin alone or combined with metformin and /or pioglitazone were r and omized ( 1:1 ) to double-blind treatment with linagliptin  5 mg once daily or placebo for ≥52 weeks . The basal insulin dose was kept unchanged for 24 weeks but could thereafter be titrated according to fasting plasma glucose levels at the investigators ’ discretion . The primary end point was the mean change in HbA1c from baseline to week 24 . The safety analysis incorporated data up to a maximum of 110 weeks . RESULTS At week 24 , HbA1c changed from a baseline of 8.3 % ( 67 mmol/mol ) by −0.6 % ( −6.6 mmol/mol ) and by 0.1 % ( 1.1 mmol/mol ) with linagliptin and placebo , respectively ( treatment difference −0.65 % [ 95 % CI −0.74 to −0.55 ] [ −7.1 mmol/mol ] ; P < 0.0001 ) . Despite the option to uptitrate basal insulin , it was adjusted only slightly upward ( week 52 , linagliptin 2.6 IU/day , placebo 4.2 IU/day ; P < 0.003 ) , result ing in no further HbA1c improvements . Frequencies of hypoglycemia ( week 24 , linagliptin 22.0 % , placebo 23.2 % ; treatment end , linagliptin 31.4 % , placebo 32.9 % ) and adverse events ( linagliptin 78.4 % , placebo 81.4 % ) were similar between groups . 
    Output:
    
Without increasing hypoglycaemia , SGLT2 inhibitors showed better glycaemic control and greater weight reduction than DPP4 inhibitors in patients with T2DM inadequately controlled with insulin .