Core Viewpoint - The article discusses the dual agonist therapy of Tirzepatide, which targets both GIP and GLP-1 receptors, highlighting its effectiveness in managing blood sugar levels and aiding weight loss in patients with type 2 diabetes [5][12]. Mechanism of Action - Tirzepatide mimics the actions of GLP-1 and GIP, promoting insulin secretion when blood sugar levels are elevated and suppressing glucagon secretion when blood sugar is normal, thus maintaining glucose balance [5][7]. - The glucose-dependent mechanism of Tirzepatide ensures that it does not induce hypoglycemia in individuals with normal blood sugar levels, making it a safer option for treating type 2 diabetes and obesity [7]. Clinical Efficacy - Clinical studies indicate that Tirzepatide significantly improves insulin sensitivity and beta-cell function in type 2 diabetes patients, with a reduction in HbA1c levels by an average of 2.0%-2.5% [10]. - In head-to-head studies, Tirzepatide demonstrated superior efficacy in lowering HbA1c compared to Semaglutide, with a reduction of 2.46% in the 15mg group versus 1.86% in the 1mg Semaglutide group [11]. Benefits of Dual Targeting - The dual action of Tirzepatide on both GIP and GLP-1 receptors enhances its effectiveness in weight loss and blood sugar control, as GIP plays a crucial role in insulin secretion [12][14]. - Research shows that GIP contributes to approximately 44% of insulin secretion post-glucose intake, while GLP-1 accounts for only 22%, emphasizing the importance of GIP in diabetes treatment [12]. Administration and Safety - Tirzepatide has a half-life of 5 days, allowing for once-weekly administration, which improves patient adherence to treatment [14][15]. - The safety profile of Tirzepatide is comparable to other GLP-1 receptor agonists, with common gastrointestinal side effects such as nausea and diarrhea [15].

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].

Core Viewpoint - Tirzepatide is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, effectively lowering blood sugar levels by mimicking the actions of GLP-1 and GIP [2][4] Mechanism of Action - Tirzepatide's glucose-lowering effect is glucose-dependent, promoting insulin release only when blood sugar levels are elevated, thus minimizing the risk of hypoglycemia in healthy individuals [4] - Traditional diabetes medications have limitations such as weight gain and hypoglycemia risk, leading to a focus on developing new drugs like tirzepatide and semaglutide, which show promising applications in type 2 diabetes treatment [5] - Clinical studies indicate that tirzepatide significantly improves insulin sensitivity and beta-cell function in type 2 diabetes patients, with an average reduction in HbA1c levels of 2.0%-2.5% [7] Clinical Efficacy - In head-to-head studies, tirzepatide demonstrated superior HbA1c reduction compared to semaglutide, with the SURPASS-2 trial showing a 2.46% reduction in the 15mg tirzepatide group versus a 1.86% reduction in the 1mg semaglutide group [7] - Tirzepatide also exhibits better control over fasting and postprandial blood glucose levels [7] Dual Target Benefits - The dual-target mechanism of tirzepatide enhances weight loss and glucose-lowering effects, with GIP playing a crucial role in insulin secretion, accounting for approximately 44% of insulin release after oral glucose intake [8][10] - GIP receptor agonists can restore insulin secretion in type 2 diabetes patients and may help reduce appetite, thereby aiding weight loss [11] Administration and Safety - Tirzepatide has a half-life of 5 days due to modifications, allowing for once-weekly administration, which improves patient adherence [10][11] - The safety profile of tirzepatide is favorable, with gastrointestinal side effects similar to other GLP-1 receptor agonists, indicating a high level of safety due to its mimicking of the body's natural weight regulation system [11]