Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective therapies for the treatment of type 2 diabetes and are all currently available as an injection. Objectives: To compare the effects of oral semaglutide with placebo (primary) and open-label subcutaneous semaglutide (secondary) on glycemic control in patients with type 2 diabetes. Design, Setting, and Patients: Phase 2, randomized, parallel-group, dosage-finding, 26-week trial with 5-week follow-up at 100 sites (hospital clinics, general practices, and clinical research centers) in 14 countries conducted between December 2013 and December 2014. Of 1106 participants assessed, 632 with type 2 diabetes and insufficient glycemic control using diet and exercise alone or a stable dose of metformin were randomized. Randomization was stratified by metformin use. Interventions: Once-daily oral semaglutide of 2.5 mg (n = 70), 5 mg (n = 70), 10 mg (n = 70), 20 mg (n = 70), 40-mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-week dose escalation (slow escalation; n = 70), 40-mg 2-week dose escalation (fast escalation, n = 70), oral placebo (n = 71; double-blind) or once-weekly subcutaneous semaglutide of 1.0 mg (n = 70) for 26 weeks. Main Outcomes and Measures: The primary end point was change in hemoglobin A1c (HbA1c) from baseline to week 26. Secondary end points included change from baseline in body weight and adverse events. Results: Baseline characteristics were comparable across treatment groups. Of the 632 randomized patients (mean age, 57.1 years [SD, 10.6]; men, 395 (62.7%); diabetes duration, 6.3 years [SD, 5.2]; body weight, 92.3 kg [SD, 16.8]; BMI, 31.7 [SD, 4.3]), 583 (92%) completed the trial. Mean change in HbA1c level from baseline to week 26 decreased with oral semaglutide (dosage-dependent range, -0.7% to -1.9%) and subcutaneous semaglutide (-1.9%) and placebo (-0.3%); oral semaglutide reductions were significant vs placebo (dosage-dependent estimated treatment difference [ETD] range for oral semaglutide vs placebo, -0.4% to -1.6%; P = .01 for 2.5 mg, Conclusions and Relevance: Among patients with type 2 diabetes, oral semaglutide resulted in better glycemic control than placebo over 26 weeks. These findings support phase 3 studies to assess longer-term and clinical outcomes, as well as safety. Trial Registration: clinicaltrials.gov Identifier: NCT01923181

Programmable Photocatalytic Activity of Multicomponent Covalent Organic Frameworks Used as Metallaphotocatalysts

The multicomponent approach allows to incorporate several functionalities into a single covalent organic framework (COF) and consequently allows the construction of bifunctional materials for cooperative catalysis. The well-defined structure of such multicomponent COFs is furthermore ideally suited for structure-activity relationship studies. We report a series of multicomponent COFs that contain acridine- and 2,2’-bipyridine linkers connected through 1,3,5-benzenetrialdehyde derivatives. The acridine motif is responsible for broad light absorption, while the bipyridine unit enables complexation of nickel catalysts. These features enable the usage of the framework materials as catalysts for light-mediated carbon−heteroatom cross-couplings. Variation of the node units shows that the catalytic activity correlates to the keto-enamine tautomer isomerism. This allows switching between high charge-carrier mobility and persistent, localized charge-separated species depending on the nodes, a tool to tailor the materials for specific reactions. Moreover, nickel-loaded COFs are recyclable and catalyze cross-couplings even using red light irradiation