***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: GLP-1 stimulates insulin secretion , suppresses glucagon secretion , delays gastric emptying , and inhibits small bowel motility , all actions contributing to the anti-diabetogenic peptide effect . Endothelial dysfunction is strongly associated with insulin resistance and type 2 diabetes mellitus and may cause the angiopathy typifying this debilitating disease . Therefore , interventions affecting both endothelial dysfunction and insulin resistance may prove useful in improving survival in type 2 diabetes patients . We investigated GLP-1 's effect on endothelial function and insulin sensitivity ( S(I ) ) in two groups : 1 ) 12 type 2 diabetes patients with stable coronary artery disease and 2 ) 10 healthy subjects with normal endothelial function and S(I ) . Subjects underwent infusion of recombinant GLP-1 or saline in a r and om crossover study . Endothelial function was measured by postischemic FMD of brachial artery , using ultrasonography . S(I ) [ in ( 10(-4 ) dl.kg(-1).min(-1))/(muU/ml ) ] was measured by hyperinsulinemic isoglycemic clamp technique . In type 2 diabetic subjects , GLP-1 infusion significantly increased relative changes in brachial artery diameter from baseline FMD(% ) ( 3.1 + /- 0.6 vs. 6.6 + /- 1.0 % , P < 0.05 ) , with no significant effects on S(I ) ( 4.5 + /- 0.8 vs. 5.2 + /- 0.9 , P = NS ) . In healthy subjects , GLP-1 infusion affected neither FMD(% ) ( 11.9 + /- 0.9 vs. 10.3 + /- 1.0 % , P = NS ) nor S(I ) ( 14.8 + /- 1.8 vs. 11.6 + /- 2.0 , P = NS ) . We conclude that GLP-1 improves endothelial dysfunction but not insulin resistance in type 2 diabetic patients with coronary heart disease . This beneficial vascular effect of GLP-1 adds yet another salutary property of the peptide useful in diabetes treatment BACKGROUND Exenatide , an incretin mimetic for adjunctive treatment of type 2 diabetes ( T2DM ) , reduced hemoglobin A(1c ) ( A1C ) and weight in clinical trials . The objective of this study was to evaluate the effects of > or = 3 years exenatide therapy on glycemic control , body weight , cardiometabolic markers , and safety . METHODS Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended , open-label clinical trial . Patients were r and omized to twice daily ( BID ) placebo , 5 mug exenatide , or 10 mug exenatide for 30 weeks , followed by 5 mug exenatide BID for 4 weeks , then 10 mug exenatide BID for > or = 3 years of exenatide exposure . Patients continued metformin and /or sulfonylureas . RESULTS 217 patients ( 64 % male , age 58 + /- 10 years , weight 99 + /- 18 kg , BMI 34 + /- 5 kg/m(2 ) , A1C 8.2 + /- 1.0 % [ mean + /- SD ] ) completed 3 years of exenatide exposure . Reductions in A1C from baseline to week 12 ( -1.1 + /- 0.1 % [ mean + /- SEM ] ) were sustained to 3 years ( -1.0 + /- 0.1 % ; p < 0.0001 ) , with 46 % achieving A1C < or = 7 % . Exenatide progressively reduced body weight from baseline ( -5.3 + /- 0.4 kg at 3 years ; p < 0.0001 ) . Patients with elevated serum alanine aminotransferase ( ALT ) at baseline ( n = 116 ) had reduced ALT ( -10.4 + /- 1.5 IU/L ; p < 0.0001 ) and 41 % achieved normal ALT . Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline ( -6.1 + /- 0.6 kg vs. -4.4 + /- 0.5 kg ; p = 0.03 ) , however weight change was minimally correlated with baseline ALT ( r = -0.01 ) or ALT change ( r = 0.31 ) . Homeostasis Model Assessment B ( HOMA-B ) , blood pressure , and aspartate aminotransferase ( AST ) all improved . A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis ( n = 151 ) .  Triglycerides decreased 12 % ( p = 0.0003 ) , total cholesterol decreased 5 % ( p = 0.0007 ) , LDL-C decreased 6 % ( p < 0.0001 ) , and HDL-C increased 24 % ( p < 0.0001 ) . Exenatide was generally well tolerated . The most frequent adverse event was mild-to-moderate nausea . The main limitation of this study is the open-label , uncontrolled nature of the study design which does not provide a placebo group for comparison . CONCLUSION Adjunctive exenatide treatment for > or = 3 years in T2DM patients result ed in sustained improvements in glycemic control , cardiovascular risk factors , and hepatic biomarkers , coupled with progressive weight reduction 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 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 . ) OBJECTIVE The gut hormone glucagon-like peptide 1 ( GLP-1 ) has insulinotropic and anorectic effects during intravenous infusion and has been proposed as a new treatment for type 2 diabetes and obesity . The effect of a single subcutaneous injection is brief because of rapid degradation . We therefore sought to evaluate the effect of infusion of GLP-1 for 48 h in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We infused GLP-1 ( 2.4 pmol.kg-1.min-1 ) or saline subcutaneously for 48 h in r and omized order in six patients with type 2 diabetes to evaluate the effect on appetite during fixed energy intake and on plasma glucose , insulin , glucagon , postpr and ial lipidemia , blood pressure , heart rate , and basal metabolic rate . RESULTS The infusion result ed in elevations of the plasma concentrations of intact GLP-1 similar to those observed after intravenous infusion of 1.2 pmol.kg-1.min-1 , previously shown to lower blood glucose effectively in type 2 diabetic patients . Fasting plasma glucose ( day 2 ) decreased from 14.1 + /- 0.9 ( saline ) to 12.2 + /- 0.7 mmol/l ( GLP-1 ) , P = 0.009 , and 24-h mean plasma glucose decreased from 15.4 + /- 1.0 to 13.0 + /- 1.0 mmol/l , P = 0.0009 . Fasting and total area under the curve for insulin and C-peptide levels were significantly higher during the GLP-1 administration , whereas glucagon levels were unchanged . Neither triglycerides nor free fatty acids were affected . GLP-1 administration decreased hunger and prospect i ve food intake and increased satiety , whereas fullness was unaffected . No side effects during GLP-1 infusion were recorded except for a brief cutaneous reaction . Basal metabolic rate and heart rate did not change significantly during GLP-1 administration . Both systolic and diastolic blood pressure tended to be lower during the GLP-1 infusion . CONCLUSIONS We conclude that 48-h continuous subcutaneous infusion of GLP-1 in type 2 diabetic patients 1 ) lowers fasting as well as meal-related plasma glucose , 2 ) reduces appetite , 3 ) has no gastrointestinal side effects , and 4 ) has no negative effect on blood pressure CONTEXT Glucagon-like peptide-1 ( GLP-1 ) and GLP-1 receptor agonists provide beneficial cardiovascular effects by protecting against ischemia and reperfusion injury . Type 2 diabetes mellitus patients have reduced glycolysis in the heart . OBJECTIVE We hypothesized 
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RESULTS The results showed that GLP-1 agent treatment in patients with T2DM and /or CVD led to significantly improved regional left ventricular contractile parameters ( including peak left systolic tissue velocity and strain ) and global left ventricular performance ( including stroke volume , ejection fraction , and left ventricular chambers ) compared with patients receiving placebo .
GLP-1 agent treatment in T2DM and /or CVD patients is associated with a modest but significant increase in the odds of left ventricular contractile parameters and left ventricular performance compared with patients having received placebo , which may be indicative of additional cardiovascular benefits for these patients