***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: Abstract Introduction The aim of the present study was to determine the effect of sitagliptin on microalbuminuria in patients with type 2 diabetes mellitus . Material s and Methods A total of 85 patients with type 2 diabetes mellitus ( age > 20 years , < 80 years , hemoglobin A1c [ HbA1c ] < 8.4 % ) were r and omized to patients taking sitagliptin 50 mg or other oral glucose‐lowering agents .  The following parameters were evaluated at 0 , 3 and 6 months after the treatment : bodyweight , blood pressure , HbA1c , fasting plasma glucose , fasting plasma insulin , low‐density lipoprotein cholesterol , high‐density lipoprotein cholesterol , triglycerides , estimated glomerular filtration rate and urinary albumin excretion . The primary outcome was changes in urinary albumin excretion at 6 months . Results Significant and comparable falls in HbA1c and fasting plasma glucose were found in both groups . However , sitagliptin significantly reduced urinary albumin excretion within 6 months , especially in patients with high urinary albumin at baseline . A total of 27 patients with normoalbuminuria showed a reduction in urinary albumin excretion , suggesting that sitagliptin prevents the development of albuminuria . A total of 15 patients with albuminuria  showed a reduction in urinary albumin excretion , suggesting the beneficial effect of sitagliptin in the early stage of diabetic nephropathy . There was a significant correlation between improvement of proteinuria and that of diastolic blood pressure . Conclusions The results suggested that sitagliptin improved albuminuria , in addition to improving glucose . The mechanism of the reduction of albuminuria by sitagliptin could be a direct effect , as well as an increase in active glucagon‐like peptide‐1 , independently affecting blood pressure , bodyweight and glucose metabolism . This trial was registered with the University Hospital Medical Information Network ( UMIN no. # 000010871 ) AIM To assess the safety and efficacy of the potent and selective dipeptidyl peptidase-4 inhibitor linagliptin 5 mg when given for 24 weeks to patients with type 2 diabetes who were either treatment-naive or who had received one oral antidiabetes drug ( OAD ) . METHODS This multicentre , r and omized , parallel group , phase III study compared linagliptin  treatment ( 5 mg once daily , n = 336 ) with placebo ( n = 167 ) for 24 weeks in type 2 diabetes patients . Before r and omization , patients pretreated with one OAD underwent a washout period of 6 weeks , which included a placebo run-in period during the last 2 weeks . Patients previously untreated with an OAD underwent a 2-week placebo run-in period . The primary endpoint was the change in HbA1c from baseline after 24 weeks of treatment . RESULTS Linagliptin treatment result ed in a placebo-corrected change in HbA1c from baseline of -0.69 % ( p < 0.0001 ) at 24 weeks . In patients with baseline HbA1c ≥ 9.0 % , the adjusted reduction in HbA1c was 1.01 % ( p < 0.0001 ) . Patients treated with linagliptin were more likely to achieve a reduction in HbA1c of ≥0.5 % at 24 weeks than those in the placebo arm ( 47.1 and 19.0 % , respectively ; odds ratio , OR = 4.2 , p < 0.0001 ) . Fasting plasma glucose improved by -1.3 mmol/l ( p < 0.0001 ) with linagliptin vs. placebo , and linagliptin produced an adjusted mean reduction from baseline after 24 weeks in 2-h postpr and ial glucose of -3.2 mmol/l ( p < 0.0001 ) . Statistically significant and relevant treatment differences were observed for proinsulin/insulin ratio ( p = 0.025 ) , Homeostasis Model Assessment -%B ( p = 0.049 ) and disposition index ( p = 0.0005 ) . There was no excess of hypoglycaemic episodes with linagliptin vs. placebo and no patient required third-party intervention . Mild or moderate renal impairment did not influence the trough plasma levels of linagliptin . CONCLUSIONS Monotherapy with linagliptin produced a significant , clinical ly meaningful and sustained improvement in glycaemic control , accompanied by enhanced parameters of β-cell function . The safety profile of linagliptin was comparable with that of placebo BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents , including saxagliptin , a dipeptidyl peptidase 4 ( DPP-4 ) inhibitor , are unclear . METHODS We r and omly assigned 16,492 patients with type 2 diabetes who had a history of , or were at risk for , cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years . Physicians were permitted to adjust other medications , including antihyperglycemic agents . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . RESULTS A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group ( 7.3 % and 7.2 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio with saxagliptin , 1.00 ; 95 % confidence interval [ CI ] , 0.89 to 1.12 ; P=0.99 for superiority ; P<0.001 for noninferiority ) ; the results were similar in the " on-treatment " analysis ( hazard ratio , 1.03 ; 95 % CI , 0.91 to 1.17 ) . The major secondary end point of a composite of cardiovascular death , myocardial infa rct ion , stroke , hospitalization for unstable angina , coronary revascularization , or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group ( 12.8 % and 12.4 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio , 1.02 ; 95 % CI , 0.94 to 1.11 ; P=0.66 ) . More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure ( 3.5 % vs. 2.8 % ; hazard ratio , 1.27 ; 95 % CI , 1.07 to 1.51 ; P=0.007 ) . Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups ( acute pancreatitis , 0.3 % in the saxagliptin group and 0.2 % in the placebo group ; chronic pancreatitis , < 0.1 % and 0.1 % in the two groups , respectively ) . CONCLUSIONS DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events , though the rate of hospitalization for heart failure was increased . Although saxagliptin improves glycemic control , other approaches are necessary to reduce cardiovascular risk in patients with diabetes . ( Funded by AstraZeneca and Bristol-Myers Squibb ; SAVOR-TIMI 53 Clinical Trials.gov number , NCT01107886 . ) Results of the main Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial indicate that intensive glucose lowering increases cardiovascular and all-cause mortality . As the contribution of mild-to-moderate chronic kidney disease ( CKD ) to these risks is not known , we assessed the impact on cardiovascular outcomes in this population . Renal function data were available on 10,136 patients of the original ACCORD cohort . Of those , 6,506 were free of CKD at baseline and 3,636 met the criteria for CKD . Participants were r and omly assigned to a treatment strategy of either intensive or st and ard glycemic goal . The primary outcome , all-cause and cardiovascular mortality , and prespecified secondary outcomes were evaluated . Risk for the primary outcome was 87 % higher in patients with than in those without CKD ( hazard ratio of 1.866 ; 95 % CI : 1.651 - 2.110 ) . All prespecified secondary outcomes were 1.5 to 3 times more frequent in patients with than in those without CKD . In patients with CKD , compared with st and ard therapy , intensive glucose lowering was significantly associated with both 31 % higher all-cause mortality ( 1.306 : 1.065 - 1.600 ) and 41 % higher cardiovascular mortality ( 1.412 : 1.052 - 1.892 ) . No significant effects were found in patients without CKD . Thus , in high-risk patients with type II diabetes , mild and moderate CKD is associated with increased cardiovascular risk .  Intensive glycemic control significantly increases the risk of cardiovascular and all-cause mortality in this population 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 . Mean body weight remained unchanged ( week 52 , linagliptin −0.30 kg , placebo −0.04 kg ) . CONCLUSIONS Linagliptin added to basal insulin therapy significantly improved glycemic control relative to placebo without increasing hypoglycemia or body weight OBJECTIVE To compare the efficacy and safety of weekly albiglutide with daily sitagliptin , daily glimepiride , and placebo . Research Design And Methods Patients with type 2 diabetes receiving metformin were r and omized to albiglutide ( 30 mg ) , sitagliptin ( 100 mg ) , glimepiride ( 2 mg ) , or placebo . Blinded dose titration for albiglutide ( to 50 mg ) and glimepiride ( to 4 mg ) was based on predefined hyperglycemia criteria . The primary end point was change in HbA1c from baseline at week 104 . Secondary end points included fasting plasma glucose ( FPG ) , weight , and time to hyperglycemic rescue . RESULTS Baseline characteristics were similar among the albiglutide ( n = 302 ) , glimepiride ( n = 307 ) , sitagliptin ( n = 302 ) , and placebo ( n = 101 ) groups .  Baseline HbA1c was 8.1 % ( 65.0 mmol/mol ) ; mean age was 54.5 years . The mean doses for albiglutide and glimepiride at week 104 were 40.5 and 3.1 mg , respectively . At week 104 , albiglutide significantly reduced HbA1c compared with placebo ( −0.9 % [ −9.8 mmol/mol ] ; P < 0.0001 ) , sitagliptin ( −0.4 % [ −4.4 mmol/mol ] ; P = 0.0001 ) , and glimepiride ( −0.3 % [ −3.3 mmol/mol ] ; P = 0.0 
    Output:
    
Conclusions : Dipeptidyl peptidase-4 inhibitors in patients with chronic kidney disease caused a modest reduction in hemoglobin A1c  versus placebo , but not when compared with sulfonylureas or albiglutide , or when used in patients on dialysis .
Additional active-comparator studies are needed to further eluci date the role of dipeptidyl peptidase-4 inhibitors in patients with chronic kidney disease stages 3–5 or on dialysis