***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 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 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 baseline to 24 months . Results The baseline-adjusted change in E/e′ during 24 months was significantly lower in the sitagliptin group than in the conventional group ( −0.18 ± 0.55 vs. 1.91 ± 0.53 , p = 0.008 ) , irrespective of a higher E/e′ value at baseline in the sitagliptin group . In analysis of covariance , sitagliptin treatment was significantly associated with change in E/e′ over 24 months ( β = −9.959 , p = 0.001 ) , independent of other clinical variables at baseline such as blood pressure , HbA1c , and medications for diabetes . Changes in other clinical variables including blood pressure and glycemic parameters , and echocardiographic parameters , such as cardiac structure and systolic function , were comparable between the two groups . There was also no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive C-reactive protein between the two groups during the study period . Conclusions Adding sitagliptin to conventional antidiabetic regimens in patients with T2DM for 24 months attenuated the annual exacerbation in the echocardiographic parameter of diastolic dysfunction ( E/e′ ) independent of other clinical variables such as blood pressure and glycemic control . Trial registration UMIN000004490 ( University Hospital Medical Information Network Clinical Trials ) . https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005356 ; registered November 1 , Background Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress . This study aim ed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor , vildagliptin , or a thiazolidinedione , pioglitazone , on glycemic variability and oxidative stress in patients with type 2 diabetes . Methods In this open label , r and omised , active-controlled , pilot trial , individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin ( 50 mg twice daily , n=17 )  or pioglitazone ( 15 mg once daily , n=14 ) treatment groups for 16 weeks . Glycemic variability was assessed by calculating the mean amplitude of glycemic excursions ( MAGE ) , which was obtained from continuous glucose monitoring . Urinary 8-iso prostagl and in F2α , serum oxidised low density lipoprotein , and high-sensitivity C-reactive protein were used as markers of oxidative stress or inflammation . Results Both vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment . Vildagliptin also significantly reduced the MAGE ( from 93.8±38.0 to 70.8±19.2 mg/dL , P=0.046 ) , and mean st and ard deviation of 24 hours glucose ( from 38±17.3 to 27.7±6.9 , P=0.026 ) ; however , pioglitazone did not , although the magnitude of decline was similar in both groups . Markers of oxidative stress or inflammation including urinary 8-iso prostagl and in F2α did not change after treatment in both groups . Conclusion In this 16-week treatment trial , vildagliptin , but not pioglitazone , reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy , although a reduction of oxidative stress markers was not observed The aim of the study was to compare the effects of the addition of sitagliptin or metformin to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients on body weight , glycemic control , beta-cell function , insulin resistance , and inflammatory state parameters .  One hundred fifty-one patients with uncontrolled type 2 diabetes mellitus ( glycated hemoglobin [ HbA(1c ) ] > 7.5 % ) in therapy with pioglitazone 30 mg/d were enrolled in this study . We r and omized patients to take pioglitazone 30 mg plus sitagliptin 100 mg once a day , or pioglitazone 15 mg plus metformin 850 mg twice a day . We evaluated at baseline and after 3 , 6 , 9 , and 12 months these parameters : body weight , body mass index , HbA(1c ) , fasting plasma glucose ( FPG ) , postpr and ial plasma glucose ( PPG ) , fasting plasma insulin ( FPI ) , homeostasis model assessment insulin resistance index ( HOMA-IR ) , homeostasis model assessment beta-cell function index , fasting plasma proinsulin ( Pr ) , Pr/FPI ratio , adiponectin , resistin ( R ) , tumor necrosis factor-alpha ( TNF-alpha ) , and high-sensitivity C-reactive protein . A decrease of body weight and body mass index was observed with metformin , but not with sitagliptin , at the end of the study . We observed a comparable significant decrease of HbA(1c ) , FPG , and PPG and a significant increase of homeostasis model assessment beta-cell function index compared with baseline in both groups without any significant differences between the 2 groups . Fasting plasma insulin , fasting plasma Pr , Pr/FPI ratio , and HOMA-IR values were decreased in both groups even if the values obtained with metformin were significantly lower than the values obtained with sitagliptin . There were no significant variations of ADN , R , or TNF-alpha with sitagliptin , whereas a significant increase of ADN and a significant decrease of R and TNF-alpha values were recorded with metformin . A significant decrease of high-sensitivity C-reactive protein value was obtained in both groups without any significant differences between the 2 groups . There was a significant correlation between HOMA-IR decrease and ADN increase , and between HOMA-IR decrease and R and TNF-alpha decrease in pioglitazone plus metformin group after the treatment . The addition of both sitagliptin or metformin to pioglitazone gave an improvement of HbA(1c ) , FPG , and PPG ; but metformin led also to a decrease of body weight and to a faster and better improvement of insulin resistance and inflammatory state parameters , even if sitagliptin produced a better protection of beta-cell function OBJECTIVE : To evaluate the effect of dipeptidyl-peptidase-4 ( DPP-4 ) inhibitor vildagliptin on high sensitivity C-reactive protein ( hsCRP ) and arterial stiffness ( AS ) in patients with type 2 diabetes ( T2DM ) . DESIGN : Sixty-four drug-naive diabetic patients , with inadequate glycemic control , participated in this r and omized , open-label study . Half of the patients received metformin 1700 mg/d and the other half of them received metformin 1700 mg/d plus vildagliptin 100 mg/d . AS was measured by carotid-femoral Pulse Wave Velocity ( cfPWV ) . Body weight ( BW ) , body mass index ( BMI ) , blood pressure ( BP ) , hsCRP , glycosylated hemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) , lipid profile , albumin/creatinine ratio ( ACR ) , fasting insulin , C-peptide , homeostasis model assessment of insulin resistance ( HOMA-IR ) and homeostasis model assessment of β-cell function ( HOMA-β ) were also assessed at baseline and after 6 months . RESULTS : Vildagliptin in combination with metformin had a beneficial influence on hsCRP , HbA1c , C-peptide and HOMA-β index ( p < 0.05 ) but had no effect on cfPWV , BP , BW , BMI , lipid profile , ACR and HOMA-IR compared with metformin alone ( p = NS ) . CONCLUSIONS : We have found that the addition of vildagliptin to metformin for a period of six months decreased hsCRP , improved glycemic control and β-cell function but had no effect on AS in drug-naive patients with T2DM OBJECTIVE Recent experimental studies have shown that dipeptidyl peptidase 4 ( DPP-4 ) inhibitors have antiatherosclerotic benefits in glucagon-like peptide 1–dependent and –independent manners . The current study investigated the effects of alogliptin , a DPP-4 inhibitor , on the progression of carotid atherosclerosis in patients with type 2 diabetes mellitus ( T2DM ) . RESEARCH DESIGN AND METHODS This prospect i ve , r and omized , open-label , blinded-end point , multicenter , parallel-group , comparative study included 341 patients with T2DM free of a history of apparent cardiovascular diseases recruited at 11 clinical units and r and omly allocated to treatment with alogliptin ( n = 172 ) or conventional treatment ( n = 169 ) . Primary outcomes were changes in mean common and maximum intima-media thickness ( IMT ) of the carotid artery measured by carotid arterial echography during a 24-month treatment period . RESULTS Alogliptin treatment had a more potent glucose-lowering effect than the conventional treatment ( −0.3 ± 0.7 % vs. −0.1 ± 0.8 % , P = 0.004 ) without an increase of hypoglycemia . Changes in the mean common and the right and left maximum IMT of the carotid arteries were significantly greater after alogliptin treatment than after conventional treatment ( −0.026 mm [ SE 0.009 ] vs. 0.005 mm [ SE 0.009 ] , P = 0.022 ; −0.045 mm [ SE 0.018 ] vs. 0.011 mm [ SE 0.017 ] , P = 0.025 , and −0.079 mm [ SE 0.018 ] vs. −0.015 mm [ SE 0.018 ] , P = 0.013 , respectively ) . CONCLUSIONS Alogliptin treatment attenuated the 
    Output:
    
Conclusions DDP-4i effectively reduced serum CRP levels and showed no stronger effect than traditional oral antidiabetic agents .