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

Association between tryptophan hydroxylase gene polymorphism and painful non-osseous temporomandibular disorders

[Abstract not Available

Three-Dimensional Stress State Around Corrosive Cavities on Pressure Vessels

Internal surfaces of pressure vessels used in many industrial sectors are subjected to corrosive effects leading to cavities. In this study, corrosive cavities on investigated pressure vessels are classified according to their shapes and dimensions. Distribution of stress was experimentally investigated around regions of different types of cavities using three-dimensional photoelastic models. An empirical expression is proposed to determine where maximum stress occurs in type of ellipsoidal cavity in the case of uniaxial loading. The obtained results show quite high stress levels around the cavity regions in pressure vessels, which increase the risk of crack formation.</jats:p

ROMATOID ARTRITLI HASTALARDA GOZ BULGULARI

Ophthalmic findings of 31 patients (22 female, 9 male, age range 16-58) with rheumatoid arthritis (RA) were evaluated. The incidence of ocular pathology was found 45.16%, 32.25% of patients had keratoconjunctivitis sicca, 6.45% had filamantary keratitis and 3.23% had nodular scleritis. The probability of ocular pathology was found to be higher in patients with longer duration of (RA). The mean duration of the disease in patients with ocular pathology (13.30+4.32) was significantly higher than the mean duration in patients without ocular pathology (7.29+3.31) (p<0.001)

Periodontal treatment of two siblings with juvenile hyaline fibromatosis

Background and Aim: Juvenile hyaline fibromatosis (JHF) is an autosomal recessive disease that presents with multiple subcutaneous nodular tumours, gingival fibromatosis, flexion contractures of the joint and hyaline material accumulation in extracellular area. Recently, the causative gene for JHF, capillary morphogenesis protein 2 (CMG2) was identified. In this case report, periodontal status, treatment and follow-up together with histopathologic evaluation of gingival tissue specimens and mutation screening of two JHF cases are presented. Case Reports: A 10-year-old female (case 1) and her 3-year-old brother (case 2) were first examined in our department with a complaint of gingival hyperplasia in 1991. Symptoms of the disease were detected in two of four siblings in the family. Several gingivectomy operations were carried out over 11 years with hygiene motivation and initial phase therapy. After the last gingivectomy operation in 2002, the patients were reviewed frequently. Results and Conclusions: Although there was linear marginal gingival inflammation, no remarkable enlargement was noted at last appointment. Histopathological findings showed increased amounts of subepithelial nodular connective tissue, thinned epithelial mucosa, separated inter-cellular bridges and decreased numbers of connective tissue cells in gingival tissue samples. Electron microscopic examinations supported the histopathological findings. Mutation screening of CMG2 demonstrated that the siblings were homozygous for a pathogenic missense mutation, V386F. Our clinical findings demonstrate that gingivectomy is useful and frequent periodontal visits are important for maintaining oral hygiene and decreasing growth rate of gingiva in JHF