Tirzepatide Improved Markers of Islet Cell Function (Fasting Glucagon and HOMA2-B) and Insulin Sensitivity (Fasting Insulin and HOMA2-IR) Compared to Semaglutide in People with Type 2 Diabetes

Question Does tirzepatide (TZP) improve markers of islet cell function and insulin sensitivity compared to semaglutide 1mg (SEMA) in people with type 2 diabetes (T2D)?

Methodology In a Phase 3 trial of 1879 people with T2D on background metformin (mean age 56.6 years; T2D duration 8.6 years; baseline HbA1c 8.3% [67mmol/mol]] BMI 34.2 kg/m2) (SURPASS-2), TZP achieved significantly greater HbA1c and weight reductions with all doses (5, 10 and 15mg) vs SEMA. Here we assessed the changes in fasting markers of islet cell function and insulin sensitivity by mixed model repeated measures in the modified intent-to-treat population.

Results At 40 weeks, all TZP doses improved HOMA2-B, calculated with C-peptide, as indicated by a significant increase by 97-120% on average with TZP, compared to 84% with SEMA. Fasting glucagon levels, adjusted for fasting serum glucose, significantly decreased by 53-55% on average with TZP 10 and 15mg doses compared with SEMA (48%). All TZP doses improved insulin sensitivity as reflected by a significant decrease by 16-24% on average of HOMA2-IR, calculated with insulin, compared to a decrease by 5% with SEMA. Fasting insulin levels were also significantly reduced by 9-21% on average with all TZP doses compared to an increase of 0.6% with SEMA.

Conclusion The GIP/GLP-1 receptor agonist TZP significantly improved markers of islet cell function and insulin sensitivity compared to selective GLP-1 receptor agonist SEMA in people with T2D.

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Artikel online veröffentlicht:
02. Mai 2023