Pancreatic Safety of Sitagliptin in the TECOS Study.

Abstract

OBJECTIVE:

We evaluated the incidence of acute pancreatitis and pancreatic cancer in patients with type 2 diabetes and cardiovascular disease who were treated with sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i).

RESEARCH DESIGN AND METHODS:

In the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study, a cardiovascular safety study of sitagliptin, all suspected cases of acute pancreatitis and pancreatic cancer were collected prospectively for 14,671 participants during a median follow-up time of 3 years, and were adjudicated blindly.

RESULTS:

Baseline differences were minimal between participants confirmed to have no pancreatic events, acute pancreatitis, or pancreatic cancer. Among those participants randomized to receive sitagliptin, 23 (0.3%) (vs. 12 randomized to receive placebo [0.2%]) had pancreatitis (hazard ratio 1.93 [95% CI 0.96-3.88], P = 0.065; 0.107 vs. 0.056/100 patient-years), with 25 versus 17 events, respectively. Severe pancreatitis (two fatal) occurred in four individuals allocated to receive sitagliptin. Cases of pancreatic cancer were numerically fewer with sitagliptin (9 [0.1%]) versus placebo (14 [0.2%]) (hazard ratio 0.66 [95% CI 0.28-1.51], P = 0.32; 0.042 vs. 0.066 events/100 patient-years). Meta-analysis with two other DPP-4i cardiovascular outcome studies showed an increased risk for acute pancreatitis (risk ratio 1.78 [95% CI 1.13-2.81], P = 0.01) and no significant effect for pancreatic cancer (risk ratio 0.54 [95% CI 0.28-1.04], P = 0.07).

CONCLUSIONS:

Pancreatitis and pancreatic cancer were uncommon events with rates that were not statistically significantly different between the sitagliptin and placebo groups, although numerically more sitagliptin participants developed pancreatitis and fewer developed pancreatic cancer. Meta-analysis suggests a small absolute increased risk for pancreatitis with DPP-4i therapy.

• Authors: John B Buse, M Angelyn Bethel, Jennifer B Green, Susanna R Stevens, Yuliya Lokhnygina, Pablo Aschner, Carlos Raffo Grado, Tsvetalina Tankova, Julio Wainstein, Robert Josse, John M Lachin, Samuel S Engel, Keyur Patel, Eric D Peterson, Rury R Holman, TECOS Study Group
• Journal: Diabetes care (Diabetes Care) Vol. 40 Issue 2 Pg. 164-170 (Feb 2017) ISSN: 1935-5548 [Electronic] United States
• PMID: 27630212 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2017 by the American Diabetes Association.

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Sitagliptin Phosphate

Topics

• Acute Disease
• Aged
• Cardiovascular Diseases (drug therapy)
• Diabetes Mellitus, Type 2 (drug therapy)
• Dipeptidyl-Peptidase IV Inhibitors (administration & dosage, adverse effects)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms (chemically induced, diagnosis)
• Pancreatitis (chemically induced, diagnosis)
• Proportional Hazards Models
• Risk Factors
• Sitagliptin Phosphate (administration & dosage, adverse effects)
• Treatment Outcome