Letters Safety of GLP-1 drugs

Report all increases in serum amylase in patients starting incretins

BMJ 2013; 347 doi: http://dx.doi.org/10.1136/bmj.f5333 (Published 05 September 2013) Cite this as: BMJ 2013;347:f5333

Re: Report all increases in serum amylase in patients starting incretins

To the editor

The introduction of incretin therapies into clinical practice has led to debate over whether they increase pancreatic enzymes. Dr Lengyel and other investigators1,2 have recommended caution when starting incretin therapy to avoid unexpected pancreatitis and pancreatic cancer by maintaining continuous clinical observation and performing appropriate laboratory tests. In recent years, elevated pancreatic enzymes, which vary considerably among individuals without clinical symptoms, have been sporadically reported.2,3 Tokuyama et al.3 reported low-grade increases in pancreatic amylase and lipase (up to 20 U/L and 30 U/L, respectively) after starting dipeptidyl peptidase-4 inhibitor therapy in patients with type 2 diabetes mellitus. For this reason, some physicians may withdraw incretin therapy in patients with a slight increase in serum amylase of 10–20 IU/ml, for example, interpreting this as a sign of pancreatitis.

In our previous study, we found low serum amylase levels in patients with diabetes, metabolic syndrome, and obesity.4 Theoretically, a mild increase in serum amylase levels within the normal range or from low to normal levels might represent a potential beneficial effect of incretin therapy on glucose homeostasis and on the endocrine–exocrine relationship, especially in individuals with appreciable weight loss. However, it is unknown whether the improvement in the endocrine–exocrine relationship is mediated by improvements in insulin action and/or via glucagon-like peptide-1 receptors expressed in the exocrine pancreas. In patients stating incretin therapy, measurement of pancreatic enzymes before and after several months of treatment will help to distinguish between unwanted outcomes, including the future development of pancreatitis, and the desired effects of incretin therapy. Unfortunately, there is currently inadequate evidence to determine the likely range of the increase in pancreatic enzymes that reflects the development of pancreatitis.

It is also essential to consider other relevant confounding factors, especially alcohol consumption and renal function, which contribute to the development of pancreatitis and affect serum amylase levels. Clearly, it is important to accumulate further data from patients worldwide to examine the clinical relevance of increases in pancreatic enzymes during incretin therapy in patients with type 2 diabetes mellitus.

Kei Nakajima
Internal Physician
Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
E-mail: keinaka@josai.ac.jp

References
1. Lengyel Z. Report all increases in serum amylase in patients starting incretins. BMJ 2013;347:f5333.
2. Lando HM, Alattar M, Dua AP. Elevated amylase and lipase levels in patients using glucagonlike peptide-1 receptor agonists or dipeptidyl-peptidase-4 inhibitors in the outpatient setting. Endocr Pract 2012;18:472-7.
3. Tokuyama H, Kawamura H, Fujimoto M, Kobayashi K, Nieda M, Okazawa T, Takemoto M, Shimada F. A low-grade increase of serum pancreatic exocrine enzyme levels by dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes. Diabetes Res Clin Pract 2013;100:e66-9.
4. Nakajima K, Nemoto T, Muneyuki T, Kakei M, Fuchigami H, Munakata H. Low serum amylase in association with metabolic syndrome and diabetes: A community-based study. Cardiovasc Diabetol 2011;10:34.

Competing interests: No competing interests
06 November 2013
Kei Nakajima
Internal Physician
Josai University
1-1 Keyakidai, Sakado, Saitama
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