Risk of Malignant Neoplasia with Glucagon-Like Peptide-1 Receptor Agonist Treatment in Patients with Type 2 Diabetes: A Meta-Analysis

Abstract

Background. Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs, but there is concern that they may increase the risk of malignant neoplasia. The present meta-analysis examined the safety of GLP-1 receptor agonists with regard to malignant neoplasia. Methods. We analyzed data from randomized controlled trials with a minimum duration of 24 weeks that assessed the incidence of neoplasms in type 2 diabetes patients receiving GLP-1 receptor agonists compared with placebo or other hypoglycemic drugs. We searched the MEDLINE, Embase, and Cochrane databases with a language restriction of English through October 1, 2018, and carried out a meta-analysis of the available trial data using a fixed effects model to calculate odds ratios (ORs) for neoplasia. Results. Thirty-four relevant articles, providing data for 50452 patients, were included in the meta-analysis. Compared with the incidence of malignant neoplasia with placebo or other interventions, no increase in malignant neoplasm formation was observed with the use of GLP-1 receptor agonists (OR 1.04, 95% confidence interval (CI) 0.94–1.15; p=0.46), liraglutide (OR 1.08, 95% CI 0.91–1.27; p=0.38), exenatide (OR 1.00, 95% CI 0.86–1.16; p=1.00), semaglutide (OR 0.89, 95% CI 0.35–2.22; p=0.80), or albiglutide (OR 1.07, 95% CI 0.23–4.88; p=0.93). A subanalysis of trials lasting longer than 3 years also showed no increase in the neoplasia risk with GLP-1 receptor agonist use (OR 1.03, 95% CI 0.92–1.15; p=0.60). Between-trial statistical heterogeneity was low for all comparisons. Conclusion. GLP-1 receptor agonists can be used without safety concerns related to malignant neoplasia in patients with type 2 diabetes.

Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52-week, randomized, open-label extension of the PIONEER 7 trial

“… 3 A meta-analysis including 3446 patients treated with subcutaneous semaglutide for up to 104 weeks and 419 patients treated with oral semaglutide for 26 weeks concluded that there was no increased risk of malignant neoplasms with semaglutide when compared with placebo or other glucose-lowering treatments (OR (95% CI) 0.89 (0.35 to 2.22); p=0.80). 19 Consistent with other studies of oral semaglutide, 1–10 no clustering of malignancies to specific organ systems was observed.…”

GLP-1 and Intestinal Diseases

“…Furthermore, in a large interventional study of 9341 participants with type 2 diabetes, liraglutide treatment did not increase neoplasm incidence [ 82 ]. This conclusion was supported by a meta-analysis including 50,453 patients from randomized controlled trials, assessing the incidence of neoplasms in type 2 diabetic patients receiving GLP-1 receptor agonists compared with placebo or other hypoglycemic drugs; in this study, there was no increase in malignant neoplasm formation upon GLP-1 agonist use [ 83 ].…”

Oral semaglutide in patients with type 2 diabetes and cardiovascular disease, renal impairment, or other comorbidities, and in older patients

“…Meta-analyses, as well as information collected from CVOTs involving long-term follow-up of thousands of patients, have consistently found insufficient evidence to support an increased risk of acute pancreatitis or cancer (including thyroid cancers) associated with GLP-1RAs as a class [48][49][50]. This was also suggested by data from PIONEER 6, in which acute pancreatitis was confirmed in one patient treated with oral semaglutide, and three patients receiving placebo [25].…”