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Cited by 5Metabolism, Diabetes, and CancerRenal cell carcinoma treatmentPancreatic function and diabetes

The Early Effect of Sunitinib on Insulin Clearance in Patients with Metastatic Renal Cell Carcinoma

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Thijs, Anna Maria J., Tack, Cees J., van der Graaf, Winette T. A., Rongen, Gerard A., van Herpen, Carla M. L.·2016·British Journal of Clinical Pharmacology
DOI 10.1111/bcp.12797PMC PMC4799938
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Abstract

Aims: In patients with diabetes treated with sunitinib symptomatic hypoglycaemia has been reported. To explore the mechanism of this adverse effect we performed a prospective study to investigate the effect of sunitinib on insulin concentration, insulin clearance and insulin sensitivity. Methods: We studied the early effects of sunitinib on insulin sensitivity and insulin clearance with a hyperinsulinaemic euglycaemic clamp (insulin infusion rate 60 mU m−2 min−1; steady‐state 90–120 min) in patients with renal cell carcinoma before and 1 week after the start of sunitinib 50 mg day−1. Insulin sensitivity index (S I) was defined as steady‐state glucose disposal divided by the steady‐state plasma insulin. Results: Ten patients (one with diabetes, treated with metformin) were included in the study protocol. Steady‐state insulin concentrations during the clamp increased after 1 week of sunitinib (from 128.9 ± 9.0 mU l−1 to 170.8 ± 12.8 mU l−1, P < 0.05; 95% CI on difference − 64.3, −19.6). The calculated insulin sensitivity index decreased from 0.22 ± 0.04 before to 0.18 ± 0.02 μmol kg−1 min−1 per mU l−1 insulin (P < 0.05; 95% CI on difference 0.07, 0.08). As the insulin infusion rate was similar for both clamps, the increased steady‐state insulin concentration indicates reduced insulin clearance. Conclusion: Sunitinib affects insulin clearance which could possibly lead to overexposure to insulin in patients using insulin or insulin‐secretion stimulating agents.

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  • Sunitinib stabilized tumor growth after two years of treatment but worsened hypoglycemia, an effect attributed to enhanced glucose-dependent insulin secretion and reduced insulin clearance.

    “In one published by Chen and colleagues, sunitinib stabilized tumor growth after two years of treatment but was noted to worsen hypoglycemia, an effect attributed to the drug's ability to enhance glucosedependent insulin secretion and reduce insulin clearance [96-98].”

    From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [98]

    The Results and Discussion (pages unavailable in our copy) show reduced insulin clearance after one week of sunitinib and suggest that this could cause hypoglycemia in patients using insulin or insulin-secretion-stimulating drugs. The paper does not report tumor stabilization after two years or attribute hypoglycemia to enhanced glucose-dependent insulin secretion; its Discussion instead proposes compensatory reduction in pancreatic insulin release. (LLM, conf=0.90)

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Authors
Thijs, A. M. J., Tack, C. J., van der Graaf, W. T. A., Rongen, G. A., & van Herpen, C. M. L.
Affiliations
  • Radboud University Nijmegen (NL)
  • Radboud University Medical Center (NL)
  • Department of Medical Oncology Radboudumc Nijmegen
Corresponding author
Thijs, Anna Maria J.
ORCID
Venue
British Journal of Clinical Pharmacology
Publisher
Wiley
Published
2016-01-14
Volume
81
Issue
4
Pages
768-772
ISSN
  • 0306-5251 (ISSN-L)
  • 1365-2125
DOI
10.1111/bcp.12797
PMC
PMC4799938
OpenAlex
W2179366724
Cited by
5
References
1
Citations by year
2025: 1 · 2024: 1 · 2021: 1 · 2016: 2
FWCI
0.29
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • British Journal of Clinical Pharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
sunitinib, insulin clearance, insulin sensitivity, insulin resistance, metastatic renal cell carcinoma, hypoglycemia, hyperinsulinemic-euglycemic clamp, insulin secretion, drug-drug interactions, diabetes mellitus
MeSH terms
Sunitinib, Adult, Aged, Antineoplastic Agents, Blood Glucose, Carcinoma, Renal Cell, Female, Humans, Hypoglycemia, Indoles, Insulin, Male, Middle Aged, Neoplasm Metastasis, Prospective Studies, Pyrroles, Time Factors, Glucose Clamp Technique

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