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Core Viewpoint - GIP (Gastric Inhibitory Polypeptide) plays a crucial role in insulin secretion and glucose metabolism, especially in the context of type 2 diabetes (T2D), where its function is often impaired. Recent studies highlight the significance of GIP in enhancing the efficacy of diabetes treatments, particularly through the development of dual receptor agonists like Tirzepatide [2][4]. Group 1: GIP and Its Role in Diabetes - GIP is secreted by intestinal K cells and, along with GLP-1, is classified as an incretin hormone that stimulates insulin secretion, helping to clear approximately 80% of glucose absorbed from food. In T2D patients, the function of incretins is nearly lost, making the restoration of this function vital for treatment [2]. - After oral glucose intake, GIP is responsible for about 44% of insulin secretion, while GLP-1 accounts for only 22% [2]. Group 2: Tirzepatide Overview - Tirzepatide is a modified peptide based on the GIP sequence and is recognized as a leading GLP-1/GIP dual receptor agonist. It has a half-life of 5 days, allowing for weekly administration [4]. - Clinical trials indicate that Tirzepatide outperforms GLP-1 single receptor agonists, such as Semaglutide, in controlling blood sugar and reducing weight [4]. Group 3: Efficacy of Tirzepatide - In the SURMOUNT-1 study, patients treated with Tirzepatide (5mg, 10mg, and 15mg) experienced significant weight loss of 15.4%, 19.9%, and 22.9% respectively, compared to a mere 2.1% in the placebo group over 176 weeks. Additionally, Tirzepatide reduced the risk of diabetes progression by 88% [6]. - The SURMOUNT-2 study confirmed that higher doses of Tirzepatide led to an average weight loss of 15.7% (15.6kg) in obese patients with T2D over 72 weeks, with 81.6% and 86.4% of patients in the 10mg and 15mg groups losing over 5% of their body weight, respectively [8]. - The SURMOUNT-3 trial showed a weight reduction of up to 26.6% after 12 weeks of lifestyle intervention and 72 weeks of Tirzepatide treatment [10]. - In the SURMOUNT-4 trial, participants lost an average of 26.0% of their body weight over 88 weeks, with a 21.1% reduction during the initial 36 weeks [11]. Group 4: Side Effects and Tolerability - Approximately 80% of Tirzepatide users report at least one side effect, primarily nausea, diarrhea, constipation, or vomiting, similar to those experienced with Semaglutide. Notably, 33% of patients on the highest dose of Tirzepatide reported nausea, compared to 44% for Semaglutide [12]. - Tirzepatide may have a lower frequency and milder symptoms of side effects compared to Semaglutide due to its dual action mechanism, which can mitigate some of the central nervous system-related side effects associated with GLP-1 [14].