***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: Background Left ventricular ( LV ) diastolic dysfunction is frequently observed in patients with type 2 diabetes .  Dipeptidyl peptidase-4 inhibitor ( DPP-4i ) attenuates postpr and ial hyperglycemia ( PPH ) and may have cardio-protective effects . It remains unclear whether DPP-4i improves LV diastolic function in patients with type 2 diabetes , and , if so , it is attributable to the attenuation of PPH or to a direct cardiac effect of DPP-4i . We compared the effects of the DPP-4i , sitagliptin , and the alpha-glucosidase inhibitor , voglibose , on LV diastolic function in patients with type 2 diabetes . Methods We conducted a prospect i ve , r and omized , open-label , multicenter study of 100 diabetic patients with LV diastolic dysfunction . Patients received sitagliptin ( 50 mg/day ) or voglibose ( 0.6 mg/day ) . The primary endpoints were changes in the e ’ velocity and E/e ’ ratio from baseline to 24 weeks later . The secondary efficacy measures included HbA1c , GLP-1 , lipid profiles , oxidative stress markers and inflammatory markers . Results The study was completed with 40 patients in the sitagliptin group and 40 patients in the voglibose group . There were no significant changes in the e ’ velocity and E/e ’ ratio from baseline to 24 weeks later in both groups . However , analysis of covariance demonstrated that pioglitazone use is an independent factor associated with changes in the e ’ and E/e ’ ratio . Among patients not using pioglitazone , e ’ increased and the E/e ’ ratio decreased in both the sitagliptin and voglibose groups . GLP-1 level increased from baseline to 24 weeks later only in the sitagliptin group ( 4.8 ± 4.7 vs. 7.3 ± 5.5 pmol/L , p < 0.05 ) . The reductions in HbA1c and body weight were significantly greater in the sitagliptin group than in the voglibose group ( −0.7 ± 0.6 % vs. −0.3 ± 0.4 , p < 0.005 ; −1.3 ± 3.2 kg vs. 0.4 ± 2.8 kg , p < 0.05 , respectively ) . There were no changes in lipid profiles and inflammatory markers in both groups . Conclusions Our trial showed that sitagliptin reduces HbA1c levels more greatly than voglibose does , but that neither was associated with improvement in the echocardiographic parameters of LV diastolic function  in patients with diabetes . Trial registration Registered at http://www.umin.ac.jp under Background Blood glucose control is fundamental albeit not enough to prevent diabetic macrovascular complications . Dipeptidyl peptidase-4 ( DPP-4 ) inhibitors are effective in improving metabolic parameters in patients with type 2 diabetes mellitus ( T2DM ) but little is known about its cardiovascular effects . We compared the DPP-4 inhibitor sitagliptin with bedtime NPH insulin ( NPH ) as add-on therapy in patients with T2DM , aim ing to ascertain which drug would have additional cardioprotective effects . Methods Thirty-five T2DM patients inadequately controlled with metformin plus glyburide were r and omized to receive sitagliptin ( n = 18 ) or NPH ( n = 17 ) for 24 weeks . Fasting plasma glucose , HbA1c , lipid profile , C-reactive protein , active glucagon-like peptide ( aGLP-1 ) levels , 24-hour ambulatory blood pressure measurement and comprehensive 2-dimensional echocardiogram were determined before and after treatments . Results Both sitagliptin and NPH therapies decreased HbA1c levels after 24 weeks . Fasting plasma glucose and triglyceride levels decreased in the NPH group whereas only sitagliptin increased aGLP-1 levels . Left ventricular diastolic dysfunction ( LVDD ) was detected in 58.6 % of twenty-nine patients evaluated . Beneficial effects in LVDD were observed in 75 % and 11 % of patients treated with sitagliptin and NPH , respectively ( p = 0.015 ) . Neither therapy changed C-reactive protein or blood pressure . Conclusions Sitagliptin and bedtime NPH were similarly effective on glucose control . Improvement in LVDD in T2DM patients treated with sitagliptin was suggested , probably related to the increase of aGLP-1 levels . Therefore , DPP-4 inhibitor seems to have cardioprotective effects independent of glucose control and may have a role in the prevention of diabetic cardiomyopathy In patients with diabetes and coronary artery disease , the potential negative role of sulfonylurea drugs is under intensive investigation . We assessed the effects of treatment with glibenclamide or insulin on the extension of left ventricular myocardial dysfunction induced by acute ischemia . Nineteen consecutive patients with type 2 diabetes and coronary artery disease entered the study . Each patient was r and omly assigned to either insulin or glibenclamide therapy . Treatment was crossed over after 12 weeks and maintained for another 12 weeks . At the end of each treatment , left ventricular myocardial function at rest and during dipyridamole infusion was studied by  two-dimensional echocardiography under the same conditions of metabolic control . Glibenclamide or insulin treatment did not influence the rest values of left ventricular dimensions , left ventricular ejection fraction ( LVEF ) , or wall motion score index ( WMSI ) . Dipyridamole infusion , in patients receiving glibenclamide treatment , decreased LVEF ( 43 + /- 7 vs. 37 + /- 12 % , P < 0.005 ) and increased WMSI ( 1.4 + /- 0.28 vs. 1.98 + /- 0.24 , P < 0.001 ) compared with baseline values ; during insulin treatment , LVEF ( 46 + /- 8 vs. 45 + /- 11 % , NS ) and WMSI ( 1.4 + /- 0.29 vs. 1.6 + /- 0.4 , NS ) did not change significantly . Peak stress LVEF was higher ( 45 + /- 11 vs. 37 + /- 12 % , P < 0.001 ) and WMSI lower ( 1.6 + /- 0.4 vs. 1.98 + /- 0.24 , P < 0.001 ) in patients receiving insulin . The results indicate that in patients with type 2 diabetes and coronary artery disease , ischemic myocardial dysfunction induced by dipyridamole infusion is less severe during treatment with insulin than with glibenclamide . Restitution of a preconditioning mechanism in insulin-treated patients may be the potential beneficial mechanism BACKGROUND Although experimental animal studies report many pleiotropic effects of dipeptidyl peptidase-4 inhibitors ( DPP-4i ) , their prognostic value has not been demonstrated in clinical trials . Methods and Results : Among 838 prospect ively enrolled heart failure ( HF ) patients hospitalized for acute decompensated HF , 79 treated with DPP-4i were compared with  79 propensity score-matched non-DPP-4i diabetes mellitus ( DM ) patients .  The primary endpoint was all-cause mortality ; the secondary endpoint was a composite of cardiovascular death and hospitalization . During follow-up ( 423±260 days ) , 8 patients ( 10.1 % ) in the DPP-4i group and 13 ( 16.5 % ) in the non-DPP-4i group died ( log-rank , P=0.283 ) . The DPP-4i group did not have a significantly higher rate of all-cause mortality ( log-rank , P=0.283 ) , or cardiovascular death or hospitalization ( log-rank , P=0.425 ) . In a subgroup analysis of HF with preserved ejection fraction ( HFpEF ; n=75 ) , the DPP-4i group had a significantly better prognosis  than the non-DPP-4i group regarding the primary endpoint ( log-rank , P=0.021 ) and a tendency to have better prognosis regarding the secondary endpoint ( log-rank , P=0.119 ) . In patients with HF with reduced EF ( n=83  ) , DPP-4i did not result in better prognosis . CONCLUSIONS DPP-4i did not increase the risk of adverse clinical outcomes in patients with DM and HF . DPP-4i may be beneficial in HFpEF Background — The incretin hormone glucagon-like peptide-1 ( GLP-1 ) has been shown to have cardioprotective properties in animal models of ischemia and infa rct ion due to promotion of myocardial glucose uptake and suppression of apoptosis . We investigated whether GLP-1 protected the heart from dysfunction caused by supply ischemia during percutaneous coronary intervention ( PCI ) . Methods and Results — Twenty patients with normal left ventricular ( LV ) function and single-vessel coronary disease within the left anterior descending artery undergoing elective PCI were studied . A conductance catheter was placed into the LV through the femoral artery , and pressure-volume loops were recorded at baseline and during a 1-minute low-pressure balloon occlusion at the site of the stenosis . The patients were r and omized to receive an infusion of either GLP-1(7–36 ) amide at 1.2 pmol/kg per minute or saline immediately after the first balloon occlusion . Coronary balloon occlusion caused LV stunning in the control group with cumulative LV dysfunction on subsequent occlusion that was not seen in the GLP-1 group . GLP-1 improved recovery of LV systolic and diastolic function at 30 minutes after balloon occlusion compared with control ( delta dP/dtmax from baseline , −1.6 % versus −12.2 % ; P=0.02 ) and reduced the LV dysfunction after the second balloon occlusion ( delta dP/dtmax , −13.1 % versus −25.3 % ; P=0.01 ) . Conclusions — In this pilot study , infusion of GLP-1 has been demonstrated to reduce ischemic LV dysfunction after supply ischemia during coronary balloon occlusion in humans and mitigates stunning . The findings require confirmation in a larger scale clinical trial . Clinical Trial Registration — URL : http://www.is rct n.org . Unique identifier : IS RCT N 77442023 OBJECTIVE In animal models , G-CSF based progenitor cell mobilization combined with a DPP4 inhibitor leads to increased homing of bone marrow derived progenitor cells to the injured myocardium via the SDF1/CXCR4 axis result ing in improved ejection fraction and survival after acute myocardial infa rct ion ( AMI ) . RESEARCH DESIGN AND METHODS After successful revascularization in AMI , 174 patients were r and omized 1:1 in a multi-centre , prospect i ve , placebo-controlled , parallel group , double blind , phase III efficacy and safety trial to treatment with G-CSF and Sitagliptin ( GS ) or placebo .  Diabetic and non-diabetic patients were included in our trial . The primary efficacy endpoint hierarchically combined global left and right ventricular ejection fraction changes from baseline to 6 months of follow-up ( ΔLVEF , ΔRVEF ) , as determined by cardiac MRI . RESULTS At follow-up ΔLVEF as well as ΔRVEF did not differ between the GS and placebo group . Patients in the placebo group had a similar risk for a major adverse cardiac event within 12 months of follow-up as compared to patients under GS . CONCLUSION Progenitor cell therapy comprising the use of G-CSF and Sitagliptin after successfully revascularized acute myocardial infa rct ion fails to show a beneficial effect on cardiac function and clinical events after 12 months . ( EudraCT : 2007 - 003,941 - 34 ; Clinical Trials.gov : NCT00650143 , funding : Heinz-Nixdorf foundation ) Abstract Background Diabetes is associated closely with an increased risk of cardiovascular events , including diastolic dysfunction and heart failure that leads to a shortening of life expectancy . It is therefore extremely valuable to evaluate the impact of antidiabetic agents on cardiac function . However , the influence of dipeptidyl peptidase 4 inhibitors on cardiac function is controversial and a major matter of clinical concern . We therefore evaluated the effect of sitagliptin on echocardiographic parameters of diastolic function in patients with type 2 diabetes as a sub- analysis of the PROLOGUE study . Methods Patients in the PROLOGUE study were assigned r and omly to either add-on sitagliptin treatment or conventional antidiabetic treatment . Of the 463 patients in the overall study , 115 patients ( 55 in the sitagliptin group and 60 in the conventional group ) who had complete echocardiographic data of the ratio of peak early diastolic transmitral flow velocity ( E ) to peak early diastolic mitral annular velocity ( e′ ) at baseline and after 12 and 24 months were included in this study . The primary endpoint of this post hoc sub- analysis was a comparison of the changes in the ratio of E to e′ ( E/e′ ) between the two groups from 
    Output:
    
GLP-1 agonists are more significantly associated with improved LVEF , LVESV and E/e′ ,  SGLT-2 inhibitors are more significantly associated with improved LVEDD and E/e′ , and DPP-4 inhibitors are more strongly associated with a negative impact on LV end-diastolic volume ( LVEDV ) than are placebos .
SGLT-2 inhibitors are superior to other drugs in pairwise comparisons