European journal of endocrinologyAug 1, 2026

Safety of diabetes drugs that target GLP-1 receptors in hormone-related tumors

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 3, 2026

Abstract

GLP-1 receptor expression has been observed in neuroendocrine tumors (NETs) and various nonneoplastic tissues.

GLP-1 receptor agonists (GLP-1RAs) have been used for twenty years, but safety concerns exist for patients with neuroendocrine neoplasms (NENs).
Rodent studies have shown that GLP-1R can drive the proliferation of C-cell neoplasms, leading to a black-box warning for use in certain conditions.
Preclinical studies indicate that GLP-1RAs may promote cell growth in pancreatic and small intestinal NETs.
Conflicting data from retrospective studies, randomized trials, and cancer registries do not support a widespread increase in NENs with GLP-1RA use.
Some epidemiological studies suggest potential survival benefits associated with the use of GLP-1RAs.
Significant evidence gaps remain, particularly regarding specific tumor subtypes and long-term outcomes in patients with multiple endocrine neoplasia type 1 (MEN1).

Simplified

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been in use for twenty years. There have been concerns about their safety in patients with neuroendocrine neoplasms (NENs). The reports of GLP-1 receptor (GLP-1R)-driven proliferation of C-cell neoplasms in rodent studies had led to the black-box warning against their use in patients with medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2). In this review, we have attempted to evaluate the physiological and pathological expression of GLP-1 receptors (GLP-1R) in various endocrine organs and summarise the preclinical and clinical evidence regarding the effect of GLP-1RA exposure and risk of NENs. GLP-1R expression has not only been found in nonneoplastic tissues such as neurohypophysis, duodenal glands and pancreatic islets but also in neuroendocrine tumours (NETs). Preclinical studies have demonstrated the proliferative effects of GLP-1RA in cell lines representing pancreatic NETs (panNETs) and small intestinal NETs. The available data from retrospective studies, randomized trials and cancer registries provide conflicting data and does not support a generalized increase in NENs with the use of GLP-1RA. Some epidemiological studies have even shown survival benefits associated with GLP-1RA use. In addition, significant gaps in evidence remain, such as lack of data regarding certain tumour subtypes, long-term prospective studies with NENs as the clinical endpoint and uncertainty regarding patients with multiple endocrine neoplasia type 1 (MEN1). Hence, the initiation of GLP-1RA therapy in patient with predisposition to NEN where a contraindication does not exist, should be approached cautiously with careful monitoring for long-term adverse effects.

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Safety of diabetes drugs that target GLP-1 receptors in hormone-related tumors

Abstract

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