***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: OBJECTIVE This study assessed the efficacy and safety of LixiLan , a fixed-ratio , titratable , combination of 2 units insulin glargine ( Gla-100 ) and 1 μg lixisenatide administered once daily via a single pen , versus Gla-100 in insulin-naïve type 2 diabetes on metformin . RESEARCH DESIGN AND METHODS Participants were r and omized to once-daily LixiLan ( n = 161 ) or Gla-100 ( n = 162 ) for 24 weeks , while continuing metformin . LixiLan and Gla-100 were started at 10 units/5 μg and 10 units , respectively , and titrated based on the Gla-100 requirement according to fasting plasma glucose levels . The primary objective was to test noninferiority ( upper bound of the 95 % CI ≤0.4 % ) of LixiLan in reducing HbA1c ; if met , statistical superiority was tested . Secondary objectives included body weight changes , hypoglycemia , and safety . RESULTS Baseline characteristics ( mean age 57 years , diabetes duration 6–7 years , BMI 32 kg/m2 ) were similar between groups . At week 24 , mean HbA1c was reduced from 8.0 % ( 64 mmol/mol ) at baseline to 6.3 % ( 45 mmol/mol ) and 6.5 % ( 48 mmol/mol ) with LixiLan and Gla-100 , respectively , establishing statistical noninferiority and superiority of LixiLan ( least-squared mean [ 95 % CI ] difference : −0.17 % [ −0.31 , −0.04 ] { −1.9 mmol/mol [ −3.4 , −0.4 ] } ; P = 0.01 ) . HbA1c < 7.0 % ( < 53 mmol/mol ) was achieved in 84 % and 78 % of participants ( nonsignificant ) ,  respectively . LixiLan improved 2-h postmeal plasma glucose versus Gla-100 ( least-squared mean difference : –3.17 mmol/L [ –57 mg/dL ] ; P < 0.0001 ) . Body weight was reduced with LixiLan ( –1 kg ) and increased with Gla-100 ( + 0.5 kg ; P < 0.0001 ) , with no increase in hypoglycemic events ( ∼25 % in each group ) . The incidence of nausea ( 7.5 % ) and vomiting ( 2.5 % ) was low with LixiLan . CONCLUSIONS LixiLan achieved statistically significant reductions to near-normal HbA1c levels with weight loss and no increased hypoglycemic risk , compared with insulin glargine alone , and a low incidence of gastrointestinal adverse events in type 2 diabetes inadequately controlled on metformin OBJECTIVE To compare the efficacy and safety of once-weekly semaglutide 1.0 mg s.c . with exenatide extended release ( ER ) 2.0 mg s.c . in subjects with type 2 diabetes . RESEARCH DESIGN AND METHODS In this phase 3a , open-label , parallel-group , r and omized controlled trial , 813 subjects with type 2 diabetes taking oral antidiabetic drugs  were r and omized ( 1:1 ) to semaglutide 1.0 mg or exenatide ER 2.0 mg for 56 weeks . The primary end point was change from baseline in HbA1c at week 56 . RESULTS Mean HbA1c ( 8.3 % [ 67.7 mmol/mol ] at baseline ) was reduced by 1.5 % ( 16.8 mmol/mol ) with semaglutide and 0.9 % ( 10.0 mmol/mol ) with exenatide ER ( estimated treatment difference vs. exenatide ER [ ETD ] –0.62 % [ 95 % CI –0.80 , –0.44 ] [ –6.78 mmol/mol ( 95 % CI –8.70 , –4.86 ) ] ; P < 0.0001 for noninferiority and superiority ) . Mean body weight ( 95.8 kg at baseline ) was reduced by 5.6 kg with semaglutide and 1.9 kg with exenatide ER ( ETD –3.78 kg [ 95 % CI –4.58 , –2.98 ] ; P < 0.0001 ) . Significantly more subjects treated with semaglutide ( 67 % ) achieved HbA1c < 7.0 % ( < 53 mmol/mol ) versus those taking exenatide ER ( 40 % ) . Both treatments had similar safety profiles , but gastrointestinal adverse events were more common in semaglutide-treated subjects ( 41.8 % ) than in exenatide ER – treated subjects ( 33.3 % ) ; injection-site reactions were more frequent with exenatide ER ( 22.0 % ) than with semaglutide ( 1.2 % ) . CONCLUSIONS Semaglutide 1.0 mg was superior to exenatide ER 2.0 mg in improving glycemic control and reducing body weight after 56 weeks of treatment ; the drugs had comparable safety profiles . These results indicate that semaglutide treatment is highly effective for subjects with type 2 diabetes who are inadequately controlled on oral antidiabetic drugs Background — Dipeptidyl-peptidase 4 ( DPP-4 ) inhibitors are increasingly used to accomplish glycemic targets in patients with type II diabetes mellitus . Because DPP-4 is expressed in inflammatory cells , we hypothesized that its inhibition will exert favorable effects in atherosclerosis . Methods and Results — Male LDLR−/− mice ( 6 weeks ) were fed a high-fat diet or normal chow diet for 4 weeks and then r and omized to vehicle or alogliptin , a high-affinity DPP-4 inhibitor ( 40 mg · kg−1 · d−1 ) , for 12 weeks . Metabolic parameters , blood pressure , vascular function , atherosclerosis burden , and indexes of inflammation were obtained in target tissues , including the vasculature , adipose , and bone marrow , with assessment of global and cell-specific inflammatory pathways . In vitro and in vivo assays of DPP-4 inhibition ( DPP-4i ) on monocyte activation/migration were conducted in both human and murine cells and in a short-term ApoE−/− mouse model .  DPP-4i improved markers of insulin resistance and reduced blood pressure . DPP-4i reduced visceral adipose tissue macrophage content ( adipose tissue macrophages ; CD11b+ , CD11c+ , Ly6Chi ) concomitant with upregulation of CD163 . DPP-4 was highly expressed in bone marrow – derived CD11b+ cells , with DPP-4i downregulating proinflammatory genes in these cells . DPP-4i  decreased aortic plaque with a striking reduction in plaque macrophages .  DPP-4i  prevented monocyte migration and actin polymerization in in vitro assays via Rac-dependent mechanisms and prevented in vivo migration of labeled monocytes to the aorta in response to exogenous tumor necrosis factor-&agr ; and DPP-4 . Conclusion — DPP-4i exerts antiatherosclerotic effects and reduces inflammation via inhibition of monocyte activation/chemotaxis . These findings have important implication s for the use of this class of drugs in atherosclerosis Aims To evaluate the safety and efficacy of once‐weekly dulaglutide 1.5 mg , a long‐acting glucagon‐like peptide‐1 receptor agonist , compared with placebo in patients with type 2 diabetes ( T2D ) on glimepiride monotherapy . Methods This phase III , r and omized ( 4 : 1 ; dulaglutide  : placebo ) , double‐blind , placebo‐controlled , 24‐week study compared the safety and efficacy of once‐weekly dulaglutide 1.5 mg with placebo in  sulphonylurea‐treated ( ≥half‐maximal dose , stable ≥3 months ) patients ( N = 300 ) with T2D and inadequate glycaemic control [ glycated haemoglobin ( HbA1c ) ≥7.5 and ≤9.5 % ( ≥58 mmol/mol and ≤80 mmol/mol ) ] . Analysis was carried out according to intention‐to‐treat . Results At baseline , the mean participant age was 58 years ; mean HbA1c was 8.4 % ( 68 mmol/mol ) and mean weight was 85.5 kg . Dulaglutide 1.5 mg was superior to placebo at 24 weeks for HbA1c reduction from baseline with a between‐group HbA1c difference of −1.3 % [ 95 % confidence interval ( CI ) −1.6 , −1.0 ] or ‐14 mmol/mol ( 95 % CI −17 , −11 ) ; p < 0.001 . A greater proportion of participants in the dulaglutide group reached an HbA1c level of < 7.0 % ( 53 mmol/mol ) compared with placebo ( 55.3 % vs 18.9 % ; p < 0.001 ) . Dulaglutide significantly decreased fasting serum glucose from baseline compared with placebo ( between‐group difference −1.86 mmol/l ( 95 % CI −2.58 , −1.14 ) or −33.54 mg/dl ( 95 % CI −46.55 , −20.53 ) ; p < 0.001 . Weight was decreased significantly from baseline in the dulaglutide group ( p < 0.001 ) ; the between‐group difference was not significant . The most common treatment‐emergent adverse events for dulaglutide 1.5 mg were gastrointestinal : nausea ( 10.5 % ) , diarrhoea ( 8.4 % ) and eructation ( 5.9 % ) . Total hypoglycaemia was higher with dulaglutide 1.5 mg vs placebo ( 2.37 and 0.07 events/participant/year , respectively ; p = 0.025 ) . No severe hypoglycaemia was reported . Conclusions Once‐weekly dulaglutide 1.5 mg had a favourable benefit/risk profile when added to glimepiride monotherapy OBJECTIVE To examine the efficacy and safety of lixisenatide ( 20 μg once daily , administered before the morning or evening meal ) as add-on therapy in patients with type 2 diabetes insufficiently controlled with metformin alone . RESEARCH DESIGN AND METHODS This was a 24-week , r and omized , double-blind , placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes ( HbA1c 7–10 % [ 53−86 mmol/mol ] ) . Patients were r and omized to lixisenatide morning ( n = 255 ) , lixisenatide evening ( n = 255 ) , placebo morning ( n = 85 ) , or placebo evening ( n = 85 ) injections . RESULTS Lixisenatide morning injection significantly reduced mean HbA1c versus combined placebo ( mean change −0.9 % [ 9.8 mmol/mol ] vs. −0.4 % [ 4.4 mmol/mol ] ; least squares [ LS ] mean difference vs. placebo −0.5 % [ 5.5 mmol/mol ] , P < 0.0001 ) . HbA1c was significantly reduced by lixisenatide evening injection ( mean change –0.8 % [ 8.7 mmol/mol ] vs. –0.4 % [ 4.4 mmol/mol ] ; LS mean difference –0.4 % [ 4.4 mmol/mol ] , P < 0.0001 ) . Lixisenatide morning injection significantly reduced 2-h postpr and ial glucose versus morning placebo ( mean change −5.9 vs. −1.4 mmol/L ; LS mean difference −4.5 mmol/L , P < 0.0001 ) . LS mean difference in fasting plasma glucose was significant in both morning ( –0.9 mmol/L , P < 0.0001 ) and evening ( –0.6 mmol/L , P = 0.0046 ) groups versus placebo . Mean body weight decreased to a similar extent in all groups . Rates of adverse events were 69.4 % in both lixisenatide groups and 60.0 % in the  placebo group . Rates for nausea and vomiting were 22.7 and 9.4 % for lixisenatide morning and 21.2 and 13.3 % for lixisenatide evening versus 7.6 and 2.9 % for placebo , respectively . Symptomatic hypoglycemia occurred in 6 , 13 , and 1 patient for lixisenatide morning , evening , and placebo , respectively , with no severe episodes . CONCLUSIONS In patients with type 2 diabetes inadequately controlled on 
    Output:
    
The safety profile of all the agents as compared to placebo or control were similar , with no or slight increase in the occurrence of adverse events ( AEs ) but no fatal reaction was reported .
The most common AEs of all the antidiabetic agents were gastrointestinal in nature , with several cases of hypoglycemic events .
However , among all these agents , semaglutide seems to be the most efficacious drug to improve glycemic control in terms of HbA1c .
Alogliptin has the least overall frequency of AEs compared to other treatment groups