***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: A total of 5082 men and women in the Framingham Heart Study population who were free of any glucose abnormality and aged 33 to 67 years were followed prospect ively over 14 years for the occurrence of glucose intolerance . The diagnosis of glucose intolerance was defined as developing documented hyperglycemia or being placed on justified treatment by a physician . The 14-year incidence was 6.7 % in men and 5.5 % in women . Multivariate analysis was used and future glucose intolerance in men and women was highly associated with casual blood glucose , Metropolitan Relative Weight and very low density lipoproteins at the baseline exam . Other factors showed only sex-specific or univariate associations . Obesity and lipoprotein abnormalities were shown to be independent markers in the prediction of future glucose intolerance OBJECTIVE Traditional blood glucose – lowering agents do not sustain adequate glycemic control in most type 2 diabetic patients . Pre clinical studies with exenatide have suggested sustained improvements in β-cell function . We investigated the effects of 52 weeks of treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp – derived measures of β-cell function , glycemic control , and body weight . RESEARCH DESIGN AND METHODS Sixty-nine metformin-treated patients with type 2 diabetes were r and omly assigned to exenatide ( n = 36 ) or insulin glargine ( n = 33 ) . β-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0 , at week 52 , and after a 4-week off-drug period . Additional end points included effects on glycemic control , body weight , and safety . RESULTS Treatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold ( 95 % CI 2.09–2.90 , P < 0.0001 ) greater after a 52-week exenatide treatment compared with insulin glargine treatment . Both exenatide and insulin glargine reduced A1C similarly : −0.8 ± 0.1 and −0.7 ± 0.2 % , respectively ( P = 0.55 ) . Exenatide  reduced body weight compared with insulin glargine ( difference −4.6 kg , P < 0.0001 ) . β-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period . A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy . CONCLUSIONS Exenatide  significantly improves β-cell function during 1 year of treatment compared with titrated insulin glargine . After cessation of both exenatide and insulin glargine  therapy , β-cell function and glycemic control returned to pretreatment values , suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy OBJECTIVE Intensive glucose-lowering therapy ( INT ) did not reduce macrovascular events in the recent r and omized trials , possibly because it did not improve or worsen other traditional or novel cardiovascular risk factors . RESEARCH DESIGN AND METHODS St and ard plasma lipids , cholesterol content of lipoprotein subfractions , and plasma inflammatory and prothrombotic markers were determined in a subgroup of the Veterans Affairs Diabetes Trial ( VADT ) participants ( n = 266 ) at baseline and after 9 months of INT or st and ard therapy . RESULTS INT  lowered glycated hemoglobin ( by a median of 2 % vs. a median of 0.7 % by st and ard treatment ; P < 0.0001 ) ; increased BMI ( 4 vs. 1 % ; P < 0.001 ) , total HDL ( 9 vs. 4 % ; P < 0.05 ) , HDL2 ( 14 vs. 0 % ; P = 0.009 ) , LDL2 ( 36 vs. 1 % ; P < 0.0001 ) , and plasma adiponectin ( 130 vs. 80 % ; P < 0.01 ) ; and reduced triglycerides ( −13 vs. −4 % ; P = 0.02 ) and small , dense LDL4 ( −39 vs. −13 % ; P < 0.001 ) , but had no effect on levels of plasma apolipoproteins B-100 and B-48 , C-reactive protein , interleukin-6 , lipoprotein-associated phospholipase A2 , myeloperoxidase , fibrinogen , and plasminogen activator inhibitor 1 . Incident macrovascular events were associated with baseline interleukin-6 ( hazard ratio per each quartile increase 1.33 [ 95 % CI 1.06–1.66 ] ) , total LDL ( 1.25 [ 1.01–1.55 ] ) , apolipoprotein B-100 ( 1.29 [ 1.01–1.65 ] ) , and fibrinogen ( 1.26 [ 1.01–1.57 ] ) but not changes in any cardiovascular risk factors at 9 months . CONCLUSIONS INT was associated with improved adiponectin , lipid levels , and a favorable shift in LDL and HDL subfractions after 9 months . These data suggest that the failure of INT to lower cardiovascular outcomes occurred despite generally favorable changes in st and ard and novel risk factors early in the study Abstract Background : An increase in body weight is a commonly perceived effect of insulin therapy for type 2 diabetes mellitus , and this may serve as a barrier to insulin initiation and usage . Objective : To investigate the baseline clinical and demographic factors associated with weight gain during insulin glargine therapy , and the implication s of weight change on clinical outcomes . Methods : This was a retrospective analysis of patient-level data from phase 3 or 4 r and omized controlled , treat-to-target ( fasting plasma glucose [ FPG ] ≤ 100 mg/dL ) trials evaluating basal insulin glargine for ≥ 24 weeks . The Pearson correlation coefficient and Cochran-Armitage trend statistic were used to calculate the existence of a trend between absolute and relative weight change , and relative glycated hemoglobin ( HbA1c ) change from baseline ; likelihood of achieving target HbA1c < 7.0 % ; change from baseline FPG ; insulin dose requirements ; incidence of hypoglycemia ; and adverse events . Results : Eleven studies were included , encompassing a total of 2140 patients . Patients starting insulin glargine treatment gained a mean ± st and ard deviation 1.8 ± 3.7 kg ( 4.0 ± 8.2 lb ) . Most patients had limited weight change ( ± 2.5 kg or 5.5 lb ) . Younger age , higher baseline HbA1c , and higher baseline FPG were predictive of greater weight gain ( P < 0.0001 ) . Those who gained more weight experienced the largest decrease from baseline in HbA1c and FPG . More weight gain was associated with higher insulin dose requirements , an increased risk of experiencing either symptomatic or glucose-confirmed ( < 70 mg/dL ) hypoglycemia , and more adverse events . Older patients ( > 65 years ) were less likely to gain weight or to experience glucose-confirmed hypoglycemia , but more likely to experience severe hypoglycemia . Conclusions : In this retrospective analysis of patient-level data , most patients had a stable weight ( defined as ± 2.5 kg ) after 24 weeks of insulin glargine , and weight gain varied with patient demographics . Therefore , insulin glargine can be used in these patient groups with type 2 diabetes without expectation of significant weight gain Background Both insulin and thiazolidinediones ( TZDs ) are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention . The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure . The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight , haemoglobin and natriuretic peptides . Methods Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were r and omised to receive  add-on therapy with insulin glargine or pioglitazone for 26 weeks . Echocardiographic data and blood sample s were collected from the two groups before the start of the treatment and after 26 weeks . Left ventricular end-diastolic and left atrial end-systolic volumes were quantified , weight measured and blood sample s analyzed . Results After 26 weeks of treatment , the changes in HbA1c , weight and haemoglobin were similar between the two groups . HDL increased significantly in the pioglitazone group . While there was an increase in natriuretic peptides in the pioglitazone group ( NT-proBNP 11.4 ± 19.6 to 22.8 ± 44.0 , p = 0.046 ) , the difference between the treatment groups was not significant . Left ventricular end-diastolic volume increased by 11 % and left atrial end-systolic volume by 17 % in the pioglitazone group ( Both , p < 0.05 , between treatment groups ) . There was a borderline significant increase in ejection fraction in the pioglitazone group . Conclusion This r and omised pilot- study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size . These changes were not observed with insulin glargine , which also is known to induce fluid retention . Larger r and omised trials are warranted to confirm these findings AIM We investigated the relationship between weight change and related factors in subjects with type 2 diabetes mellitus ( T2DM ) treated with liraglutide versus comparator diabetes therapies .  METHODS Twenty-six-week data from seven phase 3 , r and omized trials in the liraglutide T2DM development programme were analysed by trial and treatment group : liraglutide ( 1.2 and 1.8 mg ) , active comparator and placebo . Outcome measures included proportions of subjects in various weight change categories and their percentage weight change from baseline ; impact of body mass index ( BMI ) and gastrointestinal ( GI ) adverse events ( AEs ) on weight change and correlation of weight change with change in glycosylated haemoglobin ( HbA1c ) . RESULTS A number of subjects experienced > 5 % weight loss during the trials ( 24.4 % liraglutide 1.8 mg and 17.7 % liraglutide 1.2 mg ; 17.7 % exenatide , 10.0 % sitagliptin , 3.6 - 7.0 % sulphonylurea , 2.6 % thiazolidinedione and 2.6 % glargine ; 9.9 % placebo ) . More weight loss was seen with liraglutide 1.2 and 1.8 mg than with active comparators except exenatide . Across trials , higher initial BMI was associated with slightly greater weight loss with liraglutide . Mean weight loss increased slightly the longer GI AEs persisted . Although HbA1c reduction was slightly larger in higher weight loss categories across treatments ( including placebo ) , sample sizes were small and no clear correlation could be determined . Liraglutide-treated subjects experienced additional HbA1c reduction beyond that which appeared weight induced ; thus , not all HbA1c-lowering effect appears weight mediated . CONCLUSIONS The majority of liraglutide-treated T2DM subjects experienced weight loss in this analysis . Weight loss was greater and occurred more in glucagon-like peptide-1 receptor agonist-treated subjects than in active comparator-treated subjects OBJECTIVE Mealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient . However , this complex regimen is associated with weight gain and hypoglycemia . This study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration . RESEARCH DESIGN AND METHODS In this 30-week , open-label , multicenter , r and omized , noninferiority trial with 12 weeks prior insulin optimization , 627 patients with insufficient postoptimization glycated hemoglobin A1c ( HbA1c ) were r and omized to exenatide ( 10–20 µg/day ) or thrice-daily mealtime lispro titrated to premeal glucose of 5.6–6.0 mmol/L , both added to insulin glargine ( mean 61 units/day at r and omization ) and metformin ( mean 2,000 mg/day ) . RESULTS R and omization HbA1c and fasting glucose ( FG ) were 8.3 % ( 67 mmol/mol ) and 7.1 mmol/L for exenatide and 8.2 % ( 66 mmol/mol ) and 7.1 mm 
    Output:
    
There was no difference in the risk of all-cause mortality and adverse cardiovascular ( CV ) events  between Insulin and non-insulin GLTs .
Insulin was associated with superior reduction in HbA1c ; least reduction in weight and higher risk of hypoglycaemia .
Both showed similar proportion of patients achieving HbA1c target .
Non-insulin GLTs were associated with a higher risk in reported adverse drug events