Do Glucagon-like peptide-1 (GLP-1) analogs, such as exenatide (Byetta) and liraglutide (Victoza), increase the risk of cancer in patients with type 2 diabetes?

From the Guidelines

GLP-1 analogs like exenatide (Byetta) and liraglutide (Victoza) do not appear to significantly increase cancer risk in patients with type 2 diabetes, as evidenced by the most recent and highest quality study available 1.

Key Points to Consider

• Initial concerns about cancer risk with GLP-1 analogs arose from animal studies, but long-term human studies and meta-analyses have not shown a consistent increased risk of cancer with these medications.
• The LEADER trial, which followed patients taking liraglutide for over 3 years, showed no increased cancer risk compared to placebo, and similarly, the EXSCEL trial for exenatide showed no cancer signal 1.
• These medications work by mimicking the incretin hormone GLP-1, improving insulin secretion and reducing glucagon release, with theoretical concerns about potential effects on cell proliferation pathways, but clinical data has been reassuring.
• Patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 should avoid these medications as a precaution, and regular monitoring during treatment follows standard diabetes care protocols without additional cancer-specific screening requirements.

Important Considerations for Clinical Practice

• GLP-1 receptor agonists have been shown to reduce major adverse cardiovascular events and have benefits in patients with type 2 diabetes and high cardiovascular risk 1.
• Common adverse effects of GLP-1 receptor agonists include nausea, vomiting, and diarrhea, which are dose-dependent and can be managed with slow titration and other strategies 1.
• The use of GLP-1 receptor agonists in the peri-operative management of hyperglycemia has been investigated, showing an insulin-sparing effect and significant decreases in plasma glucose 1.

From the FDA Drug Label

Papillary thyroid carcinoma In adult glycemic control trials of liraglutide injection, there were 7 reported cases of papillary thyroid carcinoma in patients treated with liraglutide injection and 1 case in a comparator-treated patient (1.5 vs. 0. 5 cases per 1,000 patient-years).

The GLP-1 analog liraglutide may increase the risk of papillary thyroid carcinoma in patients with type 2 diabetes, as suggested by the higher incidence of this type of cancer in patients treated with liraglutide compared to those receiving a comparator treatment 2. However, the clinical significance of this finding is unclear. Key points to consider:

• The incidence of papillary thyroid carcinoma was higher in liraglutide-treated patients (1.5 cases per 1,000 patient-years) compared to comparator-treated patients (0.5 cases per 1,000 patient-years).
• Most of the reported papillary thyroid carcinomas were small (<1 cm in greatest diameter) and were diagnosed after thyroidectomy prompted by findings on protocol-specified screening. It is essential to weigh the potential benefits of GLP-1 analogs against the possible risks, including the uncertain risk of cancer, when making treatment decisions for patients with type 2 diabetes.

From the Research

GLP-1 Receptor Agonists and Cancer Risk

• The provided studies do not directly address the question of whether GLP-1 receptor agonists, such as exenatide and liraglutide, increase the risk of cancer in patients with type 2 diabetes 3, 4, 5, 6, 7.
• These studies focus on the efficacy, safety, and mechanisms of action of GLP-1 receptor agonists in the treatment of type 2 diabetes, as well as their potential benefits in reducing cardiovascular risk and weight loss.
• None of the studies mention a significant association between GLP-1 receptor agonists and an increased risk of cancer.

Key Findings on GLP-1 Receptor Agonists

• GLP-1 receptor agonists have been shown to be effective in reducing HbA1c levels, promoting weight loss, and reducing the risk of cardiovascular events in patients with type 2 diabetes 3, 4, 5, 6.
• The choice of GLP-1 receptor agonist depends on individual patient factors, such as dosing frequency, administration requirements, and cost 4, 5, 6.
• Fixed-ratio combinations of basal insulin and GLP-1 receptor agonists are available and may be beneficial for patients who require basal insulin and a GLP-1 receptor agonist 7.

Limitations of Current Evidence

• The current evidence does not provide a clear answer to the question of whether GLP-1 receptor agonists increase the risk of cancer in patients with type 2 diabetes.
• Further studies are needed to investigate the potential association between GLP-1 receptor agonists and cancer risk.