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Original Investigation |

Glucagonlike Peptide 1–Based Therapies and Risk of Hospitalization for Acute Pancreatitis in Type 2 Diabetes Mellitus:  A Population-Based Matched Case-Control Study

Sonal Singh, MD, MPH; Hsien-Yen Chang, PhD; Thomas M. Richards, MS; Jonathan P. Weiner, DrPH; Jeanne M. Clark, MD, MPH; Jodi B. Segal, MD, MPH
JAMA Intern Med. 2013;173(7):534-539. doi:10.1001/jamainternmed.2013.2720.
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Importance  Acute pancreatitis has significant morbidity and mortality. Previous studies have raised the possibility that glucagonlike peptide 1 (GLP-1)–based therapies, including a GLP-1 mimetic (exenatide) and a dipeptidyl peptidase 4 inhibitor (sitagliptin phosphate), may increase the risk of acute pancreatitis.

Objective  To test whether GLP-1–based therapies such as exenatide and sitagliptin are associated with an increased risk of acute pancreatitis. We used conditional logistic regression to analyze the data.

Design  Population-based case-control study.

Setting  A large administrative database in the United States from February 1, 2005, through December 31, 2008.

Participants  Adults with type 2 diabetes mellitus aged 18 to 64 years. We identified 1269 hospitalized cases with acute pancreatitis using a validated algorithm and 1269 control subjects matched for age category, sex, enrollment pattern, and diabetes complications.

Main Outcome Measure  Hospitalization for acute pancreatitis.

Results  The mean age of included individuals was 52 years, and 57.45% were male. Cases were significantly more likely than controls to have hypertriglyceridemia (12.92% vs 8.35%), alcohol use (3.23% vs 0.24%), gallstones (9.06% vs 1.34), tobacco abuse (16.39% vs 5.52%), obesity (19.62% vs 9.77%), biliary and pancreatic cancer (2.84% vs 0%), cystic fibrosis (0.79% vs 0%), and any neoplasm (29.94% vs 18.05%). After adjusting for available confounders and metformin hydrochloride use, current use of GLP-1–based therapies within 30 days (adjusted odds ratio, 2.24 [95% CI, 1.36-3.68]) and recent use past 30 days and less than 2 years (2.01 [1.37-3.18]) were associated with significantly increased odds of acute pancreatitis relative to the odds in nonusers.

Conclusions and Relevance  In this administrative database study of US adults with type 2 diabetes mellitus, treatment with the GLP-1–based therapies sitagliptin and exenatide was associated with increased odds of hospitalization for acute pancreatitis.

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Grahic Jump Location

Figure. Selection of cases and control subjects. Some cases and controls met more than 1 exclusion criterion. BCBS indicates Blue Cross Blue Shield Association; DCSI, Diabetes Complication Severity Index.

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