In a new study, the risk of pancreatic cancer with incretins was not increased when compared with other antihyperglycemic therapies. Incretin-based drugs, the DPP-4 inhibitors and GLP-1 receptor agonists, are increasingly used in type 2 diabetes.
Despite initial concerns regarding potential increased risk of pancreatitis or pancreatic cancer with incretin use in observational studies1, several large studies, notably SAVOR-TIMI 532 and EXAMINE3, have since found no difference between therapy with DPP-4 inhibitors and placebo.
This Danish case-control study matched 6,036 incident new cases of pancreatic cancer with 60,360 population controls who were naïve to glucose-lowering therapy. The rates of pancreatic cancer were comparable for individuals who had “ever used” glucose-lowering medications and controls.
Glucose-lowering medication |
Pancreatic cancer cases (n=6,036)
|
Population controls (n=60,360)
|
Adjusted OR
|
DPP-4 inhibitors |
100 (1.66%) |
302 (0.50%) |
3.9 |
GLP-1 receptor agonists |
33 (0.55%) |
136 (0.23%) |
2.7 |
Metformin |
886 (14.7%) |
3,676 (6.09%) |
2.7 |
Insulin |
567 (9.39%) |
1,575 (2.61%) |
3.6 |
No evidence was found for a causal association between incretin-based drugs and pancreatic cancer. Incretin therapy was not associated with increased cancer risk compared with other therapies. Insulin-based therapies conferred higher risk than other glucose-lowering medications.
The authors noted that this suggested that diabetes itself is a strong risk factor for pancreatic cancer, pointing to evidence showing that type 2 diabetes confers a 1.5- to 2-fold increased risk for acute pancreatitis and a 2-fold increased risk for pancreatic cancer.4,5
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1. Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology. 2011; 141(1):150-156. 2. Scirica BM, Bhatt DL, Braunwald E, et al; for the SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317-1326. 3. White WB, Cannon CP, Heller SR, et al; for the EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327-1325. 4. Gonzalez-Perez A, Schlienger RG, Garcia Rodriguez LA. Acute pancreatitis in association with type 2 diabetes and antidiabetic drugs. A population-based cohort study. Diabetes Care. 2010; 33(12): 2580-2585. 5. Ben Q, Xu M, Ning X, et al. Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies. Eur J Cancer. 2011;47(13):1928-1937.
Thomsen R, Christensen DH, Kahlert J, et al. Risk of pancreatic cancer associated with use of incretin-based therapy and other glucose-lowering agents: a nationwide case-control study in Denmark. Presented at the 51st EASD Annual Meeting. September 14-18, 2015; Stockholm, Sweden. Abstract #17.
Any pharmacologic agents discussed are approved for use in the United States by the U.S. Food and Drug Administration (FDA) unless otherwise noted. Consult individual package inserts for use outside of the United States.
September 2015
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