糖尿病进展风险降低94%！替尔泊肽不仅治疗，更可预防糖尿病

Core Viewpoint - Lifestyle interventions can effectively reduce the risk of progressing to type 2 diabetes in prediabetic patients, especially those who are overweight or obese. Additionally, drug treatments, particularly the dual receptor agonist tirzepatide, have gained attention for their potential in diabetes prevention [1]. SURMOUNT-1 Trial Results - The SURMOUNT-1 trial demonstrated that after 176 weeks, the proportion of participants developing type 2 diabetes in the tirzepatide group was 1.2%, compared to 12.6% in the placebo group, indicating a 94% reduction in diabetes progression risk [3]. - Even after a 17-week treatment cessation, the diabetes development rate in the tirzepatide group was 2.4%, versus 13.7% in the placebo group, showing an 88% risk reduction [3]. - Weight loss contributed over half (55.2%) to the reduction in diabetes risk [3]. Efficacy of Tirzepatide - Among patients receiving any dose of tirzepatide, 94.5% reverted from prediabetes to normal blood glucose levels, while only 60.4% in the placebo group achieved the same [5]. - In the 15 mg dose group, no participants progressed to diabetes, with only 2.8% remaining in the prediabetes category [5]. - Tirzepatide significantly reduced HbA1c levels by an average of 0.5% to 0.65% [5]. - Weight loss in the tirzepatide groups was significantly higher than in the placebo group, with average weight reductions of 12.3%, 18.7%, and 19.7% for the 5 mg, 10 mg, and 15 mg groups, respectively, compared to 1.3% in the placebo group [5]. Participant Demographics and Trial Design - The SURMOUNT-1 trial involved 1,032 participants randomly assigned to different doses of tirzepatide or placebo, with treatment lasting 176 weeks followed by a 17-week non-treatment period [8]. - All participants received lifestyle interventions, including dietary guidance and at least 150 minutes of exercise weekly, aiming for a daily caloric reduction of 500 kcal [8]. - Baseline characteristics included an average HbA1c of 5.8%, weight of approximately 236 pounds, and a BMI of 38.8 [8]. Health Improvements - The tirzepatide group showed significant improvements in various health metrics, including waist circumference reductions of 7.9 inches (15 mg), 7.2 inches (10 mg), and 5.1 inches (5 mg), compared to 1 inch in the placebo group [9]. - Blood pressure improvements were also notable, with systolic pressure decreasing by 5.9 to 8.5 mmHg and diastolic pressure by 4.2 to 5.9 mmHg in the tirzepatide group, compared to minimal changes in the placebo group [11]. - Lipid profiles improved, with HDL cholesterol increasing by an average of 14% and triglycerides decreasing by 32.4% in the tirzepatide group, compared to 2.5% and 4.2% in the placebo group, respectively [11]. Safety and Adverse Events - The mortality rate and incidence of serious adverse events were similar between the tirzepatide and placebo groups, with serious adverse event rates of 13.4%, 14.5%, 12.6%, and 11.9% for the 15 mg, 10 mg, 5 mg, and placebo groups, respectively [12]. - The most common adverse events were gastrointestinal, with nausea rates of 31.6% (15 mg), 32.8% (10 mg), and 24.3% (5 mg), compared to 11.9% in the placebo group [12]. - A notable concern was the occurrence of acute pancreatitis in the 5 mg group, leading to treatment discontinuation [13]. Innovation and Future Research - The SURMOUNT-1 trial is significant as it is the first Phase 3 clinical trial to utilize the GIP/GLP-1 dual receptor agonist tirzepatide for weight loss and diabetes prevention, with a long follow-up period [14]. - The trial results indicated an average weight loss of 20.9%, which is 2 to 5 times greater than previous diabetes prevention trials, alongside a 94% reduction in new type 2 diabetes cases [14]. - Further research is needed to determine whether weight loss reduces diabetes risk solely through improved insulin sensitivity or glucose-dependent insulin secretion [15].