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Review
. 2025 Feb 3:16:1530985.
doi: 10.3389/fendo.2025.1530985. eCollection 2025.

The agony and the efficacy: central mechanisms of GLP-1 induced adverse events and their mitigation by GIP

Jonathan D Douros  1 , Jonathan N Flak  1   2 , Patrick J Knerr  1
Affiliations
Review

The agony and the efficacy: central mechanisms of GLP-1 induced adverse events and their mitigation by GIP

Jonathan D Douros et al. Front Endocrinol (Lausanne). .
No abstract available

Keywords: GIP - glucose-dependent insulinotropic peptide; GLP-1 - glucagon-like peptide-1; incretin; obesity; pharmacology.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Tirzepatide exhits lower nausea compared to GLP-1R monoagonists across clinical trials. (A) Body weight loss, (B) HbA1c reduction, and (C) nausea reported across clinical trials as outlined. (D) Body weight loss, (E) HbA1c reduction, and (F) nausea as a function of the calculated circulating drug exposure (Concentration at steady state; Css).
Figure 2
Figure 2
The effects of tirzeaptide and semaglutide are reduced in patients with obesity and diabetes compared to patients with obesity alone. (A) Body weight loss and (B) nausea reported across clinical trials as outlined. Groups in blue were treated with semaglutide while groups in red were treated with tirzepatide. Patients with obesity and T2D are shown in solid bars, while patients with obesity but not T2D are shown in the hatched bars.
Figure 3
Figure 3
Summary of the primary brain depots for semaglutide as reported by Gabery et al. (33) and neuronal populations reported to mediate GLP-1R agonist-induced satiety (green) and food aversive, avoidant or nauseating behavior (red). Neuronal populations indicated by black arrows receive projections from pre-proglucagon positive (ProG+) neurons.
Figure 4
Figure 4
Proposed model for the suppression of GLP-1R agonist-induced nausea and emesis by GIPR agonism in the AP.
See this image and copyright information in PMC

References

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