Glucagon like peptide (GLP-1) receptor agonist is an effective therapy for patients with type 2 diabetes mellitus. GLP-1 agonists work by stimulating insulin secretion in hyperglycemia, suppressing glucagon secretion in hyperglycemia or euglycemia, delaying gastric emptying, reducing appetite, and losing weight.
Tirzepatide is a dual-glucose dependent insulinotropic polypeptide and GLP-1 receptor agonist. The half-life of tirzepatide is 5 days, thus allowing subcutaneous administration once a week. In a phase 2b trial in patients with type 2 diabetes, it was seen that administration of tirzepatide resulted in a reduction in hbA1c and body weight over a 26-week period. In comparison, semaglutide, a selective GLP-1 receptor agonist approved for the treatment of type 2 diabetes and administered once weekly at doses up to 1 mg, has shown significant efficacy in other trials. Patients receiving semaglutide experienced an average reduction in glycated hemoglobin levels of up to 1.8 percentage points and a weight reduction of up to 6.5 kg.
The study was a 40-week, open-label, parallel-group, randomized, active-controlled phase 3 study in 1,879 patients with a 1:1:1:1 ratio to receive tirzepatide at 5 mg, 10 mg, or 15 mg or semaglutide at 1 mg. The estimated mean changes from baseline in HbA1c values were - 2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide;the differences between the 5 mg, 10 mg, and 15 mg tirzepatide groups and the semaglutide group were -0.15 percentage points (confidence interval [CI], -0.28 to -0.03; p = 0.02), -0.39 percentage points (confidence interval, -0.51 to -0.26; p < 0.001), and -0.45 percentage points (confidence interval, -0.57 to -0.32; p < 0.001), respectively.
Tirzepatide at all doses was non-inferior and superior to semaglutide. Weight loss was greater with tirzepatide compared to semaglutide (p<0.001 for all comparisons). The most common side effects were gastrointestinal and were generally mild to moderate in both the tirzepatide and semaglutide groups (nausea, diarrhea, and vomiting). Of the patients receiving tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5 mg group), 0.2% (10 mg group), and 1.7% (15 mg group); hypoglycemia was reported in 0.4% of those receiving semaglutide. Serious adverse events were reported in 5%-7% of patients receiving tirzepatide and in 3% of those receiving semaglutide.
Conclusion:
Tirzepatide is a dual-glucose dependent insulinotropic polypeptide and GLP-1 receptor agonist that is being developed for the treatment of type 2 diabetes mellitus. Study results showed that tirzepatide was non-inferior and superior to semaglutide in terms of mean change in Hba1c level from baseline to 40 weeks. Weight loss was also greater with tirzepatide compared to semaglutide.
Image: Illustration (Source: pikisuperstar - Freepik)
Reference:
Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, et al. Tirzepatide versus once-weekly semaglutide in patients with type 2 diabetes. N Engl J Med. 2021;385:503-15
