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Diabet Med. 2019 Apr;36(4):491-498. doi: 10.1111/dme.13835. Epub 2018 Oct 25.

Treatment with incretins does not increase the risk of pancreatic diseases compared to older anti-hyperglycaemic drugs, when added to metformin: real world evidence in people with Type 2 diabetes.

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Statistics Unit, QIMR Berghofer Medical Research Institute.
School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
Division of Endocrinology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
Cardiology Department, Royal Brisbane and Women's Hospital and University of Queensland School of Medicine, Brisbane.
Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia.



In people with metformin-treated diabetes, to evaluate the risk of acute pancreatitis, pancreatic cancer and other diseases of the pancreas post second-line anti-hyperglycaemic agent initiation.


People with Type 2 diabetes diagnosed after 2004 who received metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4i, n = 50 095), glucagon-like peptide-1 receptor agonist (GLP-1RA, n = 12 654), sulfonylurea (n = 110 747), thiazolidinedione (n = 17 597) or insulin (n = 34 805) for at least 3 months were identified in the US Centricity Electronic Medical Records. Time to developing acute pancreatitis, other diseases of the pancreas and pancreatic cancer was estimated, balancing and adjusting anti-hyperglycaemic drug groups for appropriate confounders.


In the DPP-4i group, the adjusted mean time to acute pancreatitis was 2.63 [95% confidence intervals (CI) 2.38, 2.88] years; time to pancreatic cancer was 2.70 (2.19, 3.21) years; and time to other diseases of the pancreas was 2.73 (2.33, 3.12) years. Compared with DPP-4i, the insulin group developed acute pancreatitis 0.48 years (P < 0.01) earlier and the GLP-1RA group developed pancreatic cancer 3 years later (P < 0.01). However, with the constraint of no event within 6 months of insulin initiation, the risk of acute pancreatitis in the insulin group was insignificant. No other significant differences were observed between groups.


No significant differences in the risk of developing pancreatic diseases in those treated with various anti-hyperglycaemic drug classes were found.


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