***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: Sodium‐glucose co‐transporter‐2 ( SGLT2 ) inhibitors and glucagon‐like peptide‐1 receptor agonists ( GLP‐1RAs ) are antihyperglycaemic agents with weight‐lowering effects . The efficacy and safety of the SGLT2 inhibitor canagliflozin as add‐on therapy in Japanese patients with type 2 diabetes mellitus ( T2DM ) and inadequate glycaemic control with a GLP‐1RA ( ≥12 weeks ) were evaluated in this phase IV study . Patients received canagliflozin 100 mg once daily for 52 weeks . Efficacy endpoints included change in glycated haemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) , body weight , systolic blood pressure ( SBP ) and HDL cholesterol from baseline to week 52 . Safety endpoints included adverse events ( AEs ) , hypoglycaemia and laboratory tests . Of the 71 patients treated with canagliflozin , 63 completed the study . At 52 weeks , HbA1c was significantly reduced from baseline ( −0.70 % ; paired t test , P < .001 ) . Significant changes were also observed in FPG ( −34.7 mg/dL ) , body weight ( −4.46 % ) , SBP ( −7.90 mm Hg ) , and HDL cholesterol ( 7.60 % ; all P < .001 ) . The incidence of AEs , adverse drug reactions and hypoglycaemia was 71.8 % , 32.4 % and 9.9 % , respectively . All hypoglycaemic events were mild . These findings suggest that the long‐term combination of canagliflozin with a GLP‐1RA is effective and well tolerated in Japanese patients with T2DM BACKGROUND Glucagon-like peptide-1 ( GLP-1 ) receptor agonists and sodium-glucose co-transporter-2 ( SGLT2 ) inhibitors improve glycaemic control and reduce bodyweight in patients with type 2 diabetes through different mechanisms . We assessed the safety and efficacy of the addition of the once-weekly GLP-1 receptor agonist dulaglutide to the ongoing treatment regimen in patients whose diabetes is inadequately controlled with SGLT2 inhibitors , with or without metformin .  METHODS AWARD-10 was a phase 3b , double-blind , parallel-arm , placebo-controlled , 24-week study done at 40 clinical sites in Austria , Czech Republic , Germany , Hungary , Israel , Mexico , Spain , and the USA . Eligible adult patients ( ≥18 years ) with inadequately controlled type 2 diabetes ( HbA1c concentration ≥7·0 % [ 53 mmol/mol ] and ≤9·5 % [ 80 mmol/mol ] ) , a BMI of 45 kg/m2 or less , and taking stable doses ( > 3 months ) of an SGLT2 inhibitor ( with or without metformin )  were r and omly assigned ( 1:1:1 ) via an interactive web-response system to subcutaneous injections of either dulaglutide 1·5 mg , dulaglutide 0·75 mg , or placebo once per week for 24 weeks . Patients and investigators were masked to dulaglutide and placebo assignment , and those assessing outcomes were masked to study drug assignment . The primary objective was to test for the superiority of dulaglutide ( 1·5 mg or 0·75 mg ) versus placebo for change in HbA1c concentration from baseline at 24 weeks . All analyses were done in the intention-to-treat population , defined as all r and omly assigned patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT02597049 . FINDINGS Between Dec 7 , 2015 , and Feb 3 , 2017 , 424 patients were r and omly assigned to dulaglutide 1·5 mg ( n=142 ) , dulaglutide 0·75 mg ( n=142 ) , and placebo ( n=140 ) . One patient in the dulaglutide 0·75 mg group was excluded from the analysis because they did not receive any dose of the study drug . The reduction in HbA1c concentration at 24 weeks was larger in patients receiving dulaglutide ( least squares mean [ LSM ] for dulaglutide 1·5 mg -1·34 % [ SE 0·06 ] or -14·7 mmol/mol [ 0·6 ] ; dulaglutide 0·75 mg -1·21 % [ 0·06 ] or -13·2 mmol/mol [ 0·6 ] ) than in patients receiving placebo ( -0·54 % [ 0·06 ] or -5·9 mmol/mol [ 0·6 ] ; p<0·0001 for both groups vs placebo ) . The LSM differences were -0·79 % ( 95 % CI -0·97 to -0·61 ) or -8·6 mmol/mol ( -10·6 to -6·7 ) for dulaglutide 1·5 mg and -0·66 % ( -0·84 to -0·49 ) or -7·2 mmol/mol ( -9·2 to -5·4 ) for dulaglutide 0·75 mg ( p<0·0001 for both ) . Serious adverse events were reported for five ( 4 % ) patients in the dulaglutide 1·5 mg group , three ( 2 % ) patients in the dulaglutide 0·75 mg group , and five ( 4 % ) patients in the placebo group . Treatment-emergent adverse events were more common in patients treated with dulaglutide than in patients who received placebo , mainly because of an increased incidence of gastrointestinal adverse events . Nausea ( 21 [ 15 % ] patients in the dulaglutide 1·5 mg group vs seven [ 5 % ] in the dulaglutide 0·75 mg group vs five [ 4 % ] in the placebo group ) , diarrhoea ( eight [ 6 % ] vs 14 [ 10 % ] vs four [ 3 % ] ) , and vomiting ( five [ 4 % ] vs four [ 3 % ] vs one [ 1 % ] ) were more common with dulaglutide than with placebo . One episode of severe hypoglycaemia was reported in the dulaglutide 0·75 mg group . Two ( 1 % ) patients receiving dulaglutide 1·5 mg died , but these deaths were not considered to be related to study drug ; no deaths occurred in the other groups . INTERPRETATION Dulaglutide as add-on treatment to SGLT2 inhibitors ( with or without metformin ) result ed in significant and clinical ly relevant improvements in glycaemic control , with acceptable tolerability that is consistent with the established safety profile of dulaglutide . FUNDING Eli Lilly and Company ABSTRACT Review of : Neal B , Perkovic V , Mahaffey K , et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes . N Engl J Med . 2017;377:644–657 . The report combines the data from two trials , CANVAS and CANVAS-Renal , which were design ed to evaluate the safety and effect of canagliflozin , an SGLT-2 inhibitor , on the appearance of cardiovascular and renal events in patients with type 2 diabetes . Enrollees were patients with type 2 diabetes of at least 30 years of age , with a glycated hemoglobin of > or equal to 7.0 % and < or equal to 10.5 % . Patients either had to have preexisting cardiovascular disease or to be at elevated risk for cardiovascular disease , and to have an estimated glomerular filtration rate ( eGFR ) of > 30 ml/min . Patients were r and omized to canagliflozin at doses of either 100 mg or 300 mg or matching placebo in CANVAS , and to canagliflozin 100 mg with a possible increase to 300 mg , or placebo , in CANVAS-Renal . Physicians were instructed to continue appropriate diabetic management and other therapies in accordance with the best practice s in their community . There was a significant 14 % reduction in the combined endpoint of cardiovascular events of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke in the canagliflozin treated patients . There was also a pattern of improvement in markers of renal disease , including the change in the level and nature of albuminuria , a 40 % decrease in the glomerular filtration rate , the need for renal replacement therapy , or death from renal causes . This study exp and s the scope of SGLT-2 inhibitor therapy to prevent cardiovascular disease in diabetic patients beyond those with preexisting cardiovascular disease studied in the previous empagliflozin study , raising the question as to whether SGLT-2 inhibitor therapy should be considered appropriate for most , if not all , type 2 diabetes patients , not only to control hyperglycemia but also to reduce cardiovascular and renal events BACKGROUND Despite a broad range of pharmacological options for the treatment of type 2 diabetes , optimum glycaemic control remains challenging for many patients and new therapies are necessary . Semaglutide is a glucagon-like peptide-1 ( GLP-1 ) analogue in phase 3 development for type 2 diabetes . We assessed the efficacy , safety , and tolerability of semaglutide monotherapy , compared with placebo , in treatment-naive patients with type 2 diabetes who had insufficient glycaemic control with diet and exercise alone . METHODS We did a double-blind , r and omised , parallel-group , international , placebo-controlled phase 3a trial ( SUSTAIN 1 ) at 72 sites in Canada , Italy , Japan , Mexico , Russia , South Africa , UK , and USA ( including hospitals , clinical research units , and private offices ) . Eligible participants were treatment-naive individuals aged 18 years or older with type 2 diabetes treated with only diet and exercise alone for at least 30 days before screening , with a baseline HbA1c of 7·0%-10·0 % ( 53 - 86 mmol/mol ) . We r and omly assigned participants ( 2:2:1:1 ) to either once-weekly subcutaneously injected semaglutide ( 0·5 mg or 1·0 mg ) , or volume-matched placebo ( 0·5 mg or 1·0 mg ) , for 30 weeks via prefilled PDS290 pen-injectors . Participants did their own injections and were encouraged to administer them on the same day of each week in the same area of their body ; the time of day and proximity of meal times was not specified . We did the r and omisation with an interactive voice or web response system . Investigators , participants , and the funder of the study remained masked throughout the trial . The primary endpoint was the change in mean HbA1c from baseline to week 30 , and the confirmatory secondary endpoint was the change in mean bodyweight from baseline to week 30 . We assessed efficacy and safety in the modified intention-to-treat population ( ie , all participants who were exposed to at least one dose of study drug ) ; both placebo groups were pooled for assessment . This trial was registered with Clinical Trials.gov , number NCT02054897 . FINDINGS Between February 3 , 2014 , and August 21 , 2014 , we r and omly assigned 388 participants to treatment ; 387 received at least one dose of study medication ( 128 0·5 mg semaglutide , 130 1·0 mg semaglutide , 129 placebo ) . 17 ( 13 % ) of those assigned to 0·5 mg semaglutide , 16 ( 12 % ) assigned to 1·0 mg semaglutide , and 14 ( 11 % ) assigned to placebo discontinued treatment ; the main reason for discontinuation was gastrointestinal adverse events such as nausea . Mean baseline HbA1c was 8·05 % ( SD 0·85 ) ; at week 30 , HbA1c significantly decreased by 1·45 % ( 95 % CI -1·65 to -1·26 ) with 0·5 mg semaglutide ( estimated treatment difference vs placebo -1·43 % , 95 % CI -1·71 to -1·15 ; p<0·0001 ) , significantly decreased by 1·55 % ( -1·74 to -1·36 ) with 1·0 mg semaglutide ( estimated treatment difference vs placebo -1·53 % , -1·81 to -1·25 ; p<0·0001 ) , and non-significantly decreased by 0·02 % ( -0·23 to 0·18 ) with placebo . Mean baseline bodyweight was 91·93 kg ( SD 23·83 ) ; at week 30 , bodyweight significantly decreased by 3·73 kg ( 95 % CI -4·54 to -2·91 
    Output:
    
Conclusions SGLT2 inhibitors and GLP-1 agonists combination treatment improved glycemic control , reduced body weight , and decreased SBP without an increase in total adverse events or genital and urinary infections in patients with T2DM or obesity