Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
What is acute pancreatitis?
Acute pancreatitis is an inflammation of the pancreas which leads to leakage of pancreatic enzymes.
What causes acute pancreatitis?
Apart from certain drugs such as GLP-1 based therapies, the most common causes of pancreatitis are Gallstones and Alcohol use.
What are the main symptoms of pancreatitis?
The main symptoms are:
Why can pancreatitis be dangerous if left untreated?
If left untreated it can result in significant morbidity from sepsis, infections and respiratory failure.
What was previously known about the use of diabetes drugs and the risk of pancreatitis?
There were previous concerns about the use of the diabetes drugs Januvia (sitagliptin) and Byetta (exenatide) from animal studies and some reports submitted to the US Food and Drug Administration.
What did these reports indicate?
These reports indicated that some patients developed acute pancreatitis after taking GLP based therapies. However they were unable to rule out other causes of pancreatitis.
What are GLP-1 therapies?
These drugs, that include Byetta and Januvia, act through a variety of complementary mechanisms. GLP-1 secretion is decreased in type 2 diabetes, thus making it a logical target for treatment of type 2 diabetes. Exenatide is a GLP-1 mimetic. Januvia is a dipeptidyl peptidase IV inhibitor.
How long have GLP-1 therapies been available?
In the US they have been available since 2006.
How do GLP-1 therapies differ from other therapies for type 2 diabetes?
They have a unique mechanism of action through acting on the GLP-1 receptor and lowering blood sugar. Exenatide also causes weight loss and has less risk of hypoglycemia than other therapies for type 2 diabetes.
How many people use GLP-1 therapies?
Although the exact number is unknown, millions of patients with type 2 diabetes use GLP-1 based therapies in the US.
How did your research assess the risk of pancreatitis when using GLP-1?
We conducted a large case control study of patients with type 2 diabetes identifying cases with pancreatitis and then matched controls who did not have pancreatitis.
After adjusting for other risk factors for pancreatitis such as gallstones, obesity and alcohol use we found that the use of GLP-1 based therapies was associated with a more than 2 fold increased risk of hospitalization for acute pancreatitis compared to other therapies for type 2 diabetes.
How did your research account for other pancreatitis risk factors such as gallstones, obesity and heavy alcohol use?
We adjusted for these factors in our analysis-meaning the two fold increased risk was independent of effects of these risk factors after adjustment.
Why do you think use of GLP-1 based therapies was associated with a greater than 2 fold increased risk of hospitalization for acute pancreatitis?
This indicates that they have a significantly powerful effect on the pancreas as more than a 2 fold risk is usually considered evidence of a strong effect.
Why have concerns over the potential side effects of GLP-1, such as acute pancreatitis, only occurred after approval of the drug?
The small short term studies conducted for approval of diabetes drugs only focus on whether the drug is effective in lowering blood sugar. However these studies do not provide reliable information on serious safety concerns such as pancreatitis.
Did your research indicate the mechanism by which GLP-1 might cause acute pancreatitis?
No. However animal studies and other work has indicated these GLP-1 receptors can cause inflammation of the pancreas and even early changes in the pancreatic ducts that may potentially point to a link on the pathway from acute pancreatitis to pancreatic cancer associated with GLP-1 based therapies for type 2 diabetes.
What impact do you think your research will have on the use of GLP-1?
We hope that the research will ensure that those who intend to use GLP-1s are aware of this risk and the benefits of glucose lowering before choosing the best therapy.
What further research needs to be done on GLP-1 and acute pancreatitis?
GLPI drugs have now been shown to cause acute pancreatitis. Since most risk factors for acute pancreatitis also predispose to pancreatic cancer, studies are now needed to determine whether GLPIs also cause pancreatic cancer.
Where can readers find more information?
More information is available from our article:-
Singh S, Chang HY, Richards TM, Weiner JP, Clark JM, Segal JB. Glucagonlike Peptide 1-Based Therapies and Risk of Hospitalization for Acute Pancreatitis in Type 2 Diabetes Mellitus: A Population-Based Matched Case-Control Study. JAMA Intern Med. 2013 Feb 25:1-6. doi: 10.1001/jamainternmed.2013.2720. [Epub ahead of print] ( with an editorial by Peter Butler in JAMA Internal Medicine and Edwin Gale in the BMJ)
About Dr Sonal Singh
Dr. Singh completed his undergraduate and medical degree at Patna University, India. He trained in Internal Medicine at Unity Health System in Rochester, NY and an MPH at Johns Hopkins University.
His career includes appointments at the Wake Forest University School of Medicine and Public Health Sciences.
He is currently an Assistant Professor at Johns Hopkins Medicine with a joint appointment in the Johns Hopkins Bloomberg School of Public Health.
His research on drug safety was funded by the National Institutes of Health. Dr. Singh’s interests focus on outcomes of type 2 diabetes medications including pancreatitis, pancreatic and bladder cancer.