Gastroenterology

Gastroenterology

Volume 141, Issue 1, July 2011, Pages 150-156
Gastroenterology

Original Research
Clinical—Pancreas
Pancreatitis, Pancreatic, and Thyroid Cancer With Glucagon-Like Peptide-1–Based Therapies

https://doi.org/10.1053/j.gastro.2011.02.018Get rights and content

Background & Aims

Glucagon-like peptide-1−based therapy is gaining widespread use for type 2 diabetes, although there are concerns about risks for pancreatitis and pancreatic and thyroid cancers. There are also concerns that dipeptidyl peptidase-4 inhibitors could cause cancer, given their effects on immune function.

Methods

We examined the US Food and Drug Administration's database of reported adverse events for those associated with the dipeptidyl peptidase−4 inhibitor sitagliptin and the glucagon-like peptide-1 mimetic exenatide, from 2004−2009; data on adverse events associated with 4 other medications were compared as controls. The primary outcomes measures were rates of reported pancreatitis, pancreatic and thyroid cancer, and all cancers associated with sitagliptin or exenatide, compared with other therapies.

Results

Use of sitagliptin or exenatide increased the odds ratio for reported pancreatitis 6-fold as compared with other therapies (P < 2 × 10−16). Pancreatic cancer was more commonly reported among patients who took sitagliptin or exenatide as compared with other therapies (P < .008, P < 9 × 10−5). All other cancers occurred similarly among patients who took sitagliptin compared with other therapies (P =.20).

Conclusions

These data are consistent with case reports and animal studies indicating an increased risk for pancreatitis with glucagon-like peptide-1−based therapy. The findings also raise caution about the potential long-term actions of these drugs to promote pancreatic cancer.

Section snippets

Study Design

The primary goal of this analysis was to use the FDA AERS database to assess the association between treatment with exenatide (Byetta) or sitagliptin (Januvia) and an adverse event report of pancreatitis, where the drugs were listed as the primary suspect associated with a pancreatitis report in the database. A secondary goal was to examine the FDA AERS database for reported pancreatic or thyroid cancer associated with use of exenatide or sitagliptin. Third, we used the FDA AERS database to

Control Events

The validity of the analysis is predicated on a similar rate of reported control events for each drug in the analysis. For the 2 test drugs and 4 control drugs, this was found to be the case. However, one drug initially chosen for the analysis (pioglitazone) had an elevated control event reporting rate compared to the other drugs, which were otherwise similar in their control event rate. This was not driven by any one of the controls, but rather was an overall elevation in reported control

Discussion

We report a >6-fold increased reported adverse event rate for pancreatitis with either of the first two GLP-1−based drugs available on the market in the United States, exenatide and sitagliptin, in this analysis of the FDA AERS database.

Analysis of the FDA AERS database is not the ideal mechanism to compare adverse event rates between drugs. Limitations of the FDA AERS database, including incomplete data and reporting biases, are well-known.29 However, AERS has proven effective in similar

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    Conflicts of Interest The authors disclose no conflicts.

    Funding Supported by the Larry L. Hillblom Foundation.

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