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RCT STEP 9 - Semaglutide vs Placebo for Knee Osteoarthritis in Patients with Obesity, NEJM (2024) [PubMed abstract] The STEP 9 study enrolled 407 patients with BMI 30 and a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain Main inclusion criteria Age 18 years or older BMI 30 ACR diagnostic criteria for knee OA Moderate X-ray changes (Kellgren-Lawrence grade 2 or 3) in target knee Knee OA WOMAC pain score of 40 Main exclusion criteria Use of opioid medications Use of obesity medication within 90 days Knee injection within 90 days Baseline characteristics Average age - 56 years Average weight - 239 lbs (108.6 kg) Average BMI - 40.3 Female sex - 82% Average WOMAC pain score - 70.9 Randomized treatment groups Group 1 (271 patients): Semaglutide 2.4 mg once weekly Group 2 (136 patients): Placebo Semaglutide was started at 0.24 mg once weekly and titrated over 16 weeks to 2.4 mg The percentage change in body weight and the change in the WOMAC pain score (scale 0 - 100, with higher scores meaning worse outcomes) from baseline to week 68 Primary outcome: Results Among participants with obesity and knee osteoarthritis with moderate-to-severe pain, treatment with once-weekly injectable semaglutide resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis than placebo

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GSSCys and HEDS oxidoreductase assays Steady-state kinetics of wild type and mutant ScGrx7 and PfGrx in the GSSCys and HEDS assays were determined spectrophotometrically by monitoring the consumption of NADPH at 340 nm and 25 C using a thermostated Jasco V-650 UV/vis spectrophotometer 11,12,18

Two interim analyses of OS were prespecified, with the first specified at the time of analysis of the primary end point.[32][Level of evidence B1] The median PFS was 9.9 months in patients who received the combination versus 6.2 months in patients treated with vemurafenib plus placebo