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The metabolism of semaglutide occurs through proteolytic cleavage, a process whereby enzymes break down the peptide structure into smaller amino acid components, and beta-oxidation

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Obesity Pharmacotherapy update: OASIS 4 Once-daily Oral Semaglutide 25 mg for Weight Loss (NEJM 2025) Population: BMI 30 or 27 + comorbidity | N=307 | Randomization: 2:1 | Duration: 64 wks on-treatment Intervention: Oral semaglutide 25 mg daily + lifestyle Comparator: Placebo + lifestyle Primary outcome (wk 64): Weight change: 13.6% vs 2.2% 11.4 pp (P 40 High purine diet (red meat, seafood) Alcohol (especially beer) Obesity Hypertension, diabetes, CKD Diuretics (thiazides, loop diuretics) Genetics (enzyme defects like HGPRT deficiency) Clinical Features Acute gout attack Sudden onset, often at night Severe pain, redness, swelling Usually affects first metatarsophalangeal joint (podagra) Fever and malaise may occur Chronic gout / tophaceous gout Tophi (urate crystal deposits) in ears, fingers, toes Joint deformities Chronic arthritis Renal involvement Uric acid nephrolithiasis Chronic urate nephropathy Investigations Serum uric acid: may be elevated (not always during acute attack) Joint aspiration: monosodium urate crystals (needle-shaped, negatively birefringent under polarized light) gold standard Renal function tests Imaging: X-ray shows punched-out erosions with overhanging edges (chronic gout) Management Acute attack NSAIDs (first-line, e.g., indomethacin) Colchicine (if NSAIDs contraindicated) Corticosteroids (oral or intra-articular) Long-term / urate-lowering therapy Indicated for recurrent attacks, tophi, or renal involvement Allopurinol (xanthine oxidase inhibitor) Febuxostat (alternative) Lifestyle: reduce alcohol, high-purine foods, maintain hydration Prophylaxis during urate-lowering therapy initiation Low-dose colchicine or NSAIDs to prevent flare Acute monoarthritis of the big toe classic gout Tophi in chronic gout Joint aspiration confirms diagnosis Avoid rapid urate-lowering during acute attack (can precipitate flare) To view or add a comment, sign in Big news in obesity treatment: Wegovy now in a pill and its a game changer