Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes

Nov 25, 2020The Journal of clinical endocrinology and metabolism

Tirzepatide, a drug targeting two hormone receptors, may improve insulin-producing cell function and insulin sensitivity in type 2 diabetes

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Abstract

Tirzepatide improved markers of insulin sensitivity and beta-cell function more than dulaglutide in 316 subjects with type 2 diabetes.

  • Homeostatic model assessment (HOMA) 2-B increased significantly with tirzepatide at doses of 5, 10, and 15 mg compared to placebo.
  • Proinsulin/insulin and proinsulin/C-peptide ratios decreased significantly with tirzepatide at 10 and 15 mg compared to both placebo and dulaglutide.
  • Fasting insulin levels significantly decreased with tirzepatide at 10 and 15 mg compared to placebo and dulaglutide.
  • Improvements in insulin sensitivity markers such as adiponectin and IGFBP-1 were observed with tirzepatide at one or more doses.
  • Weight loss explained only 13% and 21% of the improvement in insulin resistance markers (HOMA2-IR) with tirzepatide at 10 and 15 mg, respectively.

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Key numbers

93% to 163%
Increase in HOMA2-B Indices
Percent change from baseline for tirzepatide doses at 26 weeks.
P ≤ .033
Decrease in Fasting Insulin Levels
Statistical significance for fasting insulin levels with tirzepatide 10 and 15 mg.
13% to 21%
Weight Loss Contribution
Percentage of improvement in HOMA2-IR explained by weight loss with tirzepatide.

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