***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 
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    Input: BACKGROUND The cardiovascular effects of adding once‐weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown . METHODS We r and omly assigned patients with type 2 diabetes , with or without previous cardiovascular disease , to receive subcutaneous injections of extended‐release exenatide at a dose of 2 mg or matching placebo once weekly . The primary composite outcome was the first occurrence of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The co primary hypotheses were that exenatide , administered once weekly , would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy . RESULTS In all , 14,752 patients ( of whom 10,782 [ 73.1 % ] had previous cardiovascular disease ) were followed for a median of 3.2 years ( interquartile range , 2.2 to 4.4 ) . A primary composite outcome event occurred in 839 of 7356 patients ( 11.4 % ; 3.7 events per 100 person‐years ) in the exenatide group and in 905 of 7396 patients ( 12.2 % ; 4.0 events per 100 person‐years ) in the placebo group ( hazard ratio , 0.91 ; 95 % confidence interval [ CI ] , 0.83 to 1.00 ) , with the intention‐to‐treat analysis indicating that exenatide , administered once weekly , was noninferior to placebo with respect to safety ( P<0.001 for noninferiority ) but was not superior to placebo with respect to efficacy ( P=0.06 for superiority ) . The rates of death from cardiovascular causes , fatal or nonfatal myocardial infa rct ion , fatal or nonfatal stroke , hospitalization for heart failure , and hospitalization for acute coronary syndrome , and the incidence of acute pancreatitis , pancreatic cancer , medullary thyroid carcinoma , and serious adverse events did not differ significantly between the two groups . CONCLUSIONS Among patients with type 2 diabetes with or without previous cardiovascular disease , the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo . ( Funded by Amylin Pharmaceuticals ; EXSCEL Clinical Trials.gov number , NCT01144338 . Background : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events . We report the effects on heart failure ( HF ) and cardiovascular death overall , in those with and without a baseline history of HF , and in other participant subgroups . Methods : The CANVAS Program ( Canagliflozin Cardiovascular Assessment Study ) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk . Participants were r and omly assigned to canagliflozin or placebo and followed for a mean of 188 weeks . The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF . Results : Participants with a history of HF at baseline ( 14.4 % ) were more frequently women , white , and hypertensive and had a history of prior cardiovascular disease  ( all P<0.001 ) . Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system , diuretics , and & bgr;-blockers at baseline ( all P<0.001 ) . Overall , cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo ( 16.3 versus 20.8 per 1000 patient-years ; hazard ratio [ HR ] , 0.78 ; 95 % confidence interval [ CI ] , 0.67–0.91 ) , as was fatal or hospitalized HF ( HR , 0.70 ; 95 % CI , 0.55–0.89 ) and hospitalized HF alone ( HR , 0.67 ; 95 % CI , 0.52–0.87 ) . The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF ( HR , 0.61 ; 95 % CI , 0.46–0.80 ) compared with those without HF at baseline ( HR , 0.87 ; 95 % CI , 0.72–1.06 ; P interaction = 0.021 ) . The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline ( all interaction P values > 0.130 ) , except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF ( P=0.03 ) . Conclusions : In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease , canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups . Benefits may be greater in those with a history of HF at baseline . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifiers : NCT01032629 and NCT01989754 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more This September issue of AOGS is especially stimulating with a blend of articles from different sub-specialities using various method ologies : r and omized controlled trials , experimental studies , cohort studies , question naire surveys and register-based follow-up studies . The guest editorial on how to reduce obesity starts with a first fresh reference to a Swedish register study that found a dose-response dependent correlation between increase in BMI /weight gain between first and second delivery , and subsequent stillbirth and infant mortality ! Importantly , pregnancy and the time period between first and second pregnancy is both a window of opportunity and key to the outcome of the second pregnancy . We may still be challenged by wishful thinking – the observational studies make us conclude that an intervention is beneficial even though RCTs do not show the expected change . For a moment we may be disappointed , but then we reconsider and realize that the chosen outcome measures are not appropriate , but a result of the limitation of the short follow up of the RCTs . The theme of obesity is different from many other issues ; obesity may change the intrauterine environment and the future health of the offspring for generations . Also , the September issue presents the first stateof-the-art review in AOGS . At the last editorial board meeting we discussed how to categorize review s. For at least the last decade , epidemiologists have seen to that all review s are systematic : when we receive a narrative review it has usually been condensed to a commentary in its own right . However , we needed a category that combines physiological , experimental and epidemiological perspectives written in a systematic fashion : not too far from a textbook chapter , but printed years before it would have been available in a textbook . We thought of “ overview ” , but chose “ state-of-the-art ” . Although some might consider this terminology preposterous , we think that when you read the publication on “ Fetal movements ” you will know what we mean . We present a high level review beyond the scope of a limited systematic literature search , including clinical experience and a large spread of references covering decades of relevant publications . Many articles in this issue are not obstetric . The first original research paper is a Danish population -based survey on gynecological cancer symptoms showing that in women who experienced one of five symptoms that might be associated with gynecologic cancer , only 20 % mentioned it to their general practitioner and of these 40 % were referred to or seen by a specialist . Among most women in Norway with leiomyosarcoma the diagnosis was not suspected prior to surgery , and since most women were menopausal the authors argue that morcellation could still be used in premenopausal women with fibromas . The authors present a balanced discussion of the use of a mechanical morcellator in laparoscopic hysterectomy , including the fear of spread of tumor cells in very few as opposed to the advantages of laparoscopic surgery . Mats Br€annstr€ om was the first to perform a successful uterus transplantation in the world . You may re-read his intriguing story of how he pursued the idea based on an urge to help a young woman , who had been hysterectomized ( 1 ) . Now , Japanese research ers have performed experimental studies on technical issues : for how long can a uterus of the cynomolgus monkey “ survive ” warm ischaemia ? ( Answer : about four hours ) . A Swedish study on antenatal lifestyle intervention to reduce weight gain in pregnancy compared st and ard antenatal care with a composite of monitoring , personalized graph and specific education . The study shows that the intervention was actually associated with a reduced weight gain shortly after delivery . However , the difference disappeared within a year ! Observational data within the trial showed that excessive weight gain shortly after delivery was associated with an even higher increase in body weight after one year . The short presentation of remaining articles in the following will illustrate the impressive coverage of this issue and may serve as appetizers : An Australian observational study of the effect of a hemostatic matrix used for hysterectomies was inconclusive , yet the authors still consider the matrix to be useful . See for yourself if you agree . Fertility manuscripts increasingly find their way to AOGS : A paper on Nordic ovarian tissue cryopreservation and transplantation report 20 years of experience . A BACKGROUND Glucagon-like peptide 1 receptor agonists differ in chemical structure , duration of action , and in their effects on clinical outcomes . The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown . We aim ed to determine the safety and efficacy of albiglutide in preventing cardiovascular death , myocardial infa rct ion , or stroke . METHODS We did a double-blind , r and omised , placebo-controlled trial in 610 sites across 28 countries . We r and omly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease ( at a 1:1 ratio ) to groups that either received a subcutaneous injection of albiglutide ( 30 - 50 mg , based on glycaemic response and tolerability ) or of a matched volume of placebo once a week , in addition to their st and ard care . Investigators used an interactive voice or web response system to obtain treatment assignment , and patients and all study investigators were masked to their treatment allocation . We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death , myocardial infa rct ion , or stroke , which was assessed in the intention-to-treat population . If non-inferiority was confirmed by an upper limit of the 95 % CI for a hazard ratio of less than 1·30 , closed testing for superiority was prespecified . This study is registered with Clinical Trials.gov , number NCT02465515 . FINDINGS Patients were screened between July 1 , 2015 , and Nov 24 , 2016 . 10 793 patients were screened and 9463 participants were enrolled and r and omly assigned to groups : 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo . On Nov 8 , 2017 , it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued , and participants returned for a final visit and discontinuation from study treatment ; the last patient visit was on March 12 , 2018 . These 9463 patients , the intention-to-treat population , were evaluated for a median duration of 1·6 years and were assessed for the primary outcome . The primary composite outcome occurred in 338 ( 7 % ) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 ( 9 % ) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group ( hazard ratio 0·78 , 95 % CI 0·68 - 0·90 ) , which indicated that albiglutide was superior to placebo ( p<0·0001 for non-inferiority ; p=0·0006 for superiority ) . The incidence of acute pancreatitis ( ten patients in the albiglutide group and seven patients in the placebo group ) , pancreatic cancer ( six patients in the albiglutide group and five patients in the placebo group ) , medullary thyroid carcinoma ( zero patients in both groups ) , and other serious adverse events did not differ between the two groups . There were three ( < 1 % ) deaths in the placebo group that were assessed by investigators , who were masked to study drug assignment , to be treatment-related and two ( < 1 % ) deaths in the albiglutide group . INTERPRETATION In patients with type 2 diabetes and cardiovascular disease , albiglutide was superior to placebo with respect to major adverse cardiovascular events . Evidence -based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes . FUNDING GlaxoSmithKline BACKG 
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The meta-regression analysis of all 12 trials showed no association of reductions of hemoglobin A1C with HF risk .
Conclusion In T2D , SGLT-2i can reduce the risk of HF that is unrelated to improved glycemic control ; DPP-4i and GLP-1 RAs behave as neutral