337-OR: Tirzepatide Improved Markers of Islet-Cell Function (Fasting Glucagon and HOMA2-B) and Insulin Sensitivity (Fasting Insulin and HOMA2-IR) Compared with Semaglutide in People with Type 2 Diabetes
Abstract
Tirzepatide (TZP) achieved significantly greater HbA1c and weight reductions with all doses (5, and 15 mg) vs. semaglutide 1 mg (SEMA) in a Phase 3 trial of 1879 people with type 2 diabetes (T2D) on background metformin (mean age 56.6 years; T2D duration 8.6 years; baseline HbA1c 8.3% [67 mmol/mol]; BMI 34.2 kg/m2) (SURPASS-2) . Changes in fasting markers of islet cell function and insulin sensitivity were assessed by mixed model repeated measures in the modified intent-to-treat population. 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 and 15 mg 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. Dual GIP/GLP-1 receptor agonist TZP significantly improved markers of islet cell function and insulin sensitivity compared to selective GLP-1 RA SEMA in people with T2D. Disclosure K. Brown: Employee; Eli Lilly and Company. L. Fernandez Lando: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. B. Bergman: Employee; Eli Lilly and Com…
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In SURPASS-2 on background metformin therapy, tirzepatide treatment resulted in greater reductions in HOMA2-IR and improvements in HOMA2-B than active comparator semaglutide 1 mg in conjunction with substantial improvements in HbA1c and body weight.
“Similarly, in SURPASS-2 on background metformin therapy, tirzepatide treatment resulted in greater reductions in HOMA2-IR and improvements in HOMA2-B than active comparator semaglutide 1 mg in conjunction with substantial improvements in HbA1c and body weight [2, 13].”
From Tirzepatide as monotherapy improved markers of beta-cell function and insulin sensitivity in type 2 diabetes (SURPASS-1). (2023) · cites this paper as [13]
HOMA2-B improvements have also been observed with tirzepatide treatment combined with metformin in independent studies.
“HOMA2-B improvements have also been observed with tirzepatide treatment combined with metformin in independent studies [13, 14].”
From Tirzepatide as monotherapy improved markers of beta-cell function and insulin sensitivity in type 2 diabetes (SURPASS-1). (2023) · cites this paper as [13]
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Lee, C. J., Mao, H., Thieu, V. T., Landó, L. F., & Thomas, M. K. (2023) · Journal of the Endocrine Society · doi:10.1210/jendso/bvad056 · Cited by 48 · see citing works
Self-citation
- Authors
- BROWN, K., LANDO, L. F., BERGMAN, B., THOMAS, M. K., LIU, B., & LEE, C.
- Affiliations
- Indianapolis, IN
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2022-06-01
- Volume
- 71
- Issue
- Supplement_1
- ISSN
- 0012-1797 (ISSN-L)
- OpenAlex
- W4281992279
- Cited by
- 4
- References
- 0
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- tirzepatide, semaglutide, type 2 diabetes, islet function, insulin sensitivity, HOMA2-IR, HOMA2-B, fasting insulin, GIP/GLP-1 receptor agonist, GLP-1 receptor agonists, metformin, weight loss, glycemic control, C-peptide
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