BACKGROUND: Recent trends in use of tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonist (RA), versus other glucose-lowering medications (GLMs) and weight-lowering medications (WLMs) remain unexplored. OBJECTIVE: To describe trends in insurance claims for GLMs and WLMs after tirzepatide approval. DESIGN: Population-based cohort study. SETTING: Claims data from a large U.S. commercial database (January 2021 to December 2023). PARTICIPANTS: Adults (aged ≥18 years) with type 2 diabetes (T2D) and without diabetes with dispensations for GLMs and WLMs. Any use was defined as medication dispensation regardless of prior use. Incident use was defined as dispensation without use in the preceding year. MEASUREMENTS: Monthly trends in medication dispensations before and after tirzepatide market entry. Tirzepatide uptake was additionally compared with initial postapproval uptake of other GLMs and WLMs. RESULTS: Tirzepatide dispensations increased markedly among adults with T2D prescribed GLMs, reaching 12.3% of all GLM dispensations by December 2023. Similar patterns were observed for sodium-glucose cotransporter-2 inhibitors (14.5% to 24.4%) and GLP-1 RAs (19.5% to 28.5%). Dispensations of other GLMs, including metformin, declined. Among adults without diabetes but prescribed WLMs, tirzepatide (0.0% to 40.6%) and semaglutide (2.4 mg) (0.0% to 32.2%) dispensations increased sharply, but semaglutide (2.0 mg) was the most frequently dispensed WLM, increasing from 37.8% to 45.7%. Dispensations of other WLMs declined. Similar trends were observed among incident users. Tirzepatide uptake was more rapid and sustained compared with initial postapproval periods for other medications. LIMITATION: Generalizability to U.S. adults without commercial health insurance is uncertain. CONCLUSION: These findings highlight the sharp uptake of tirzepatide after U.S. market entry and enhance understanding of the rapidly shifting landscape of prescribing patterns for GLMs and WLMs. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases.