Quantitative Insights into Tirzepatide and Semaglutide Using Longitudinal Systems Modeling

Clicks: 10
ID: 329384
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #433 of 449 articles by views in the journal of clinical endocrinology & metabolism

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 449 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
CONTEXT: In a 28-week clinical trial of patients with type 2 diabetes (T2D), tirzepatide 15 mg (a dual GIP/GLP-1 receptor agonist) and semaglutide 1 mg (a GLP-1 receptor agonist) both improved fasting glucose, with tirzepatide showing superior efficacy. The longitudinal metabolic mechanisms underlying this difference remain incompletely defined. OBJECTIVE: To compare the longitudinal metabolic effects of tirzepatide and semaglutide using model-based analysis of fasting measures, elucidate underlying mechanisms, and explore strategies to enhance outcomes in low responders. METHODS: A mechanistic longitudinal model was developed based on the trial data from patients treated with tirzepatide or semaglutide. The model integrates fasting glucose, fasting insulin, insulin sensitivity, and beta-cell function over time, enabling quantification of hepatic glucose production (HGP) and isolation of insulin-independent drug effects on HGP. RESULTS: Beta-cell function, as assessed by HOMA-B, initially increased and then declined as insulin sensitivity improved, a reversal of the canonical T2D progression pathway. Tirzepatide's superior fasting glucose control versus semaglutide was driven primarily by greater insulin-independent suppression of HGP. Low responders exhibited deficient HGP suppression, and simulations suggested that enhancing HGP suppression improves fasting glucose without inducing β-cell stress associated with sustained hypersecretion. Simulated enhancement of weight loss accelerated early glycemic improvement but did not further reduce long-term fasting glucose levels. CONCLUSION: Greater suppression of hepatic glucose production was associated with greater efficacy of tirzepatide 15 mg versus semaglutide 1 mg in improving fasting glucose. Therapeutic strategies targeting suppression of hepatic glucose production may provide metabolic benefit beyond direct enhancement of beta-cell function or additional weight loss.
Reference Key
openalex_W7213896756 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Boya Yang, Over Cabrera, Kieren J Mather, Arthur Sherman
Are you one of these authors? Claim your profile
Journal the journal of clinical endocrinology & metabolism
Year 2026
DOI
10.1210/clinem/dgag383
URL
https://doi.org/10.1210/clinem/dgag383
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.