Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial

Background: Oral semaglutide is the first oral formulation of a glucagon-like peptide-1 (GLP-1) receptor agonist developed for the treatment of type 2 diabetes. We aimed to compare the efficacy and safety of flexible dose adjustments of oral semaglutide with sitagliptin 100 mg. Methods: In this 52-week, multicentre, randomised, open-label, phase 3a trial, we recruited patients with type 2 diabetes from 81 sites in ten countries. Patients were eligible if they were aged 18 years or older (19 years or older in South Korea), had type 2 diabetes (diagnosed ≥90 days before screening), HbA1c of 7·5–9·5% (58–80 mmol/mol), and were inadequately controlled on stable daily doses of one or two oral glucose-lowering drugs (for 90 days or more before screening). Participants were randomly assigned (1:1) by use of an interactive web-response system, stratified by background glucose-lowering medication at screening, to oral semaglutide with flexible dose adjustments to 3, 7, or 14 mg once daily or sitagliptin 100 mg once daily. To approximate treatment individualisation in clinical practice, oral semaglutide dose could be adjusted on the basis of prespecified HbA1c and tolerability criteria. Two efficacy-related estimands were prespecified: treatment policy (regardless of treatment discontinuation or use of rescue medication) and trial product (on treatment and without use of rescue medication) for participants randomly assigned to treatment. The primary endpoint was achievement of HbA1c of less than 7% (53 mmol/mol) at week 52 and the confirmatory secondary efficacy endpoint was change in bodyweight from baseline to week 52. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02849080, and European Clinical Trials Database, EudraCT number 2015-005593-38, and an open-label extension is ongoing. Findings: Between Sept 20, 2016, and Feb 7, 2017, of 804 patients assessed for eligibility, 504 were eligible and randomly assigned to oral semaglutide (n=253) or sitagliptin (n=251). Most participants were male (285 [57%] of 504) with a mean age of 57·4 years (SD 9·9). All participants were given at least one dose of their allocated study drug except for one participant in the sitagliptin group. From a mean baseline HbA1c of 8·3% (SD 0·6%; 67 mmol/mol [SD 6·4]), a greater proportion of participants achieved an HbA1c of less than 7% with oral semaglutide than did with sitagliptin (treatment policy estimand: 58% [134 of 230] vs 25% [60 of 238]; and trial product estimand: 63% [123 of 196] vs 28% [52 of 184]). The odds of achieving an HbA1c of less than 7% was significantly better with oral semaglutide than sitagliptin (treatment policy estimand: odds ratio [OR] 4·40, 95% CI 2·89–6·70, p<0·0001; and trial product estimand: 5·54, 3·54–8·68, p<0·0001). The odds of decreasing mean bodyweight from baseline to week 52 were higher with oral semaglutide than with sitagliptin (estimated mean change in bodyweight, treatment policy estimand: −2·6 kg [SE 0·3] vs −0·7 kg [SE 0·2], estimated treatment difference [ETD] −1·9 kg, 95% CI −2·6 to −1·2; p<0·0001; and trial product estimand: −2·9 kg [SE 0·3] vs −0·8 kg [SE 0·3], ETD −2·2 kg, −2·9 to −1·5; p<0·0001). Adverse events occurred in 197 (78%) of 253 participants in the oral semaglutide group versus 172 (69%) of 250 in the sitagliptin group, and nausea was the most common adverse event with oral semaglutide (53 [21%]). Two deaths occurred in the sitagliptin group during the trial. Interpretation: Oral semaglutide, with flexible dose adjustment, based on efficacy and tolerability, provided superior glycaemic control and weight loss compared with sitagliptin, and with a safety profile consistent with subcutaneous GLP-1 receptor agonists. Funding: Novo Nordisk A/S

Affinity of Staphylococcus epidermidis to various prosthetic graft materials

yerdel, mehmet ali/0000-0002-4044-076XWOS: 000169838100010PubMed: 11421606Background. Abdominal wall hernias have always been a major problem for general surgeons. The techniques of repairing primacy, recurrent, and incisional hernias have evolved throughout the years at an accelerating trend, especially after production of prosthetic graft materials. Although looked upon with suspicion due to infection, fistula formation, and foreign body reaction, prosthetic graft materials are used deliberately in primary and recurrent hernias. The present study was,designed to evaluate bacterial adherence to frequently used prosthetic graft materials. Materials and methods. The study was carried out in five different groups with each group consisting of 10 identical samples of the same kind of prosthetic graft material. The prosthetic graft materials used in the study were polypropylene, polyglactin 910, polyester fibers, steel, and polytetrafluoroethylene (PTFE). These prosthetic graft materials were incubated in vitro with a Staphylococcus epidermidis strain which was ++++ adhesion positive. The degree of adhesion of S. epidermidis to prosthetic graft materials was assessed by the ELISA. method. Results. Vicryl grafts showed significantly minimal bacterial adhesion whereas PTFE grafts tended to have more adhesion but this did not reach a statistical significance. Other graft materials did not show any difference for bacterial adhesion (Table 3). Conclusion. These results suggest that in vitro S. epidermidis adhesion to Vicryl grafts is less than other types of prosthetic graft materials (P 2001 Academic press

Assessing the risk of asymptomatic dysplasia in parents of children with developmental hip dysplasia

The aim of this study was to investigate whether being the parents of children with developmental hip dysplasia (DDH) is a risk factor for asymptomatic dysplasia

Procalcitonin: a Novel Cardiac Marker with Prognostic Value in Acute Coronary Syndrome

Procalcitonin (PCT) is implicated as an inflammatory marker in early atherosclerosis. In order to investigate the clinical consequences of increased PCT levels in acute coronary syndrome (ACS), 77 patients (29 with non-ST-elevation myocardial infarction [MI], 34 with ST-elevation MI and 14 with unstable angina pectoris) were included and followed up for 6 months. The PCT levels were determined at initial presentation and within 48 h of admission. Five patients died during hospitalization and their PCT levels within 48 h of admission were significantly higher than survivors (n = 72) (0.588 +/- 0.56 versus 0.399 +/- 1.33 ng/ml, respectively). The PCT levels within 48 h post-admission in the nine patients who died within 6 months were also significantly higher compared with the survivors (0.451 +/- 0.44 versus 0.406 +/- 1.37 ng/ml, respectively). It is concluded that higher PCT levels within 48 h post-admission may reflect an inflammatory state that is associated with increased early and 6-month mortality

Role of Enoxaparin Resistance in Recurrent Chest Pain in the Intensive Care Unit

To investigate the relationship between anticoagulation treatment and drug resistance in chest pain, levels of factor Xa residual activity were determined in patients seen in intensive care with recurrent chest pain and compared with levels in patients who had no ischaemic events during hospitalization. A total of 122 patients aged 18 - 75 years who were admitted to hospital with acute coronary syndrome and treated with enoxaparin were included. Of these, 62 patients had recurrent chest pain while hospitalized (group A) and 60 patients had an uneventful follow-up period (group B). Patients requiring primary percutaneous transluminal coronary angioplasty and/or treatment with glycoprotein IIb/IIIa inhibitors, and those with renal failure, a high risk of bleeding or receiving anti-inflammatory drugs were excluded from the study. Median levels (+/- interquartile range) of factor Xa residual activity were significantly higher in group A compared with group B (0.68 +/- 0.29 IU/ml versus 0.34 +/- 0.33 IU/ml). It is concluded that enoxaparin resistance, resulting in high levels of factor Xa residual activity, should be considered in patients with recurrent ischaemia

Role of Enoxaparin Resistance in Recurrent Chest Pain in the Intensive Care Unit

To investigate the relationship between anticoagulation treatment and drug resistance in chest pain, levels of factor Xa residual activity were determined in patients seen in intensive care with recurrent chest pain and compared with levels in patients who had no ischaemic events during hospitalization. A total of 122 patients aged 18 - 75 years who were admitted to hospital with acute coronary syndrome and treated with enoxaparin were included. Of these, 62 patients had recurrent chest pain while hospitalized (group A) and 60 patients had an uneventful follow-up period (group B). Patients requiring primary percutaneous transluminal coronary angioplasty and/or treatment with glycoprotein IIb/IIIa inhibitors, and those with renal failure, a high risk of bleeding or receiving anti-inflammatory drugs were excluded from the study. Median levels (+/- interquartile range) of factor Xa residual activity were significantly higher in group A compared with group B (0.68 +/- 0.29 IU/ml versus 0.34 +/- 0.33 IU/ml). It is concluded that enoxaparin resistance, resulting in high levels of factor Xa residual activity, should be considered in patients with recurrent ischaemia