Experts Raise Concerns about JAMA Study and Pancreatitis Risk of Diabetes Medications

Aaron Lohr
Director, Media Relations
Phone: (240) 482-1380
Email: alohr@endo-society.org

Endocrine Society issues statement on pancreatitis risk associated with certain diabetes medications

Chevy Chase, MD— The Endocrine Society released today a statement highlighting multiple concerns regarding a recent study published in JAMA Internal Medicine by Singh et al. that suggests that treatment of type 2 diabetes with sitagliptin (Januvia®) – a DPP-4 inhibitor - or exenatide (Byetta®) – a GLP-1 analog - may be associated with an increased risk of developing acute pancreatitis severe enough to require hospitalization, a condition with potentially significant morbidity.

Singh et al. examined a large administrative U.S. database of 1.1 million persons with Type 2 diabetes mellitus and found a two-fold relative increased risk of acute pancreatitis, after adjusting for confounders and metformin use, in those taking sitagliptin or exenatide as compared with those diabetics not using these medications.  However, the crude data indicate that the absolute incidence of acute pancreatitis is quite low in both groups: 2.7 per thousand in the control group not taking the medications as compared to 4.1 per thousand in those on the medications.  It should be kept in mind that the patients in this study had other risk factors for pancreatitis and that diabetes itself is associated with an almost two-fold increase in the incidence of acute pancreatitis.

All retrospective database analyses, including that by Singh et al., suffer from common flaws:  inability to verify the diagnosis and inability to include data from individual medical records in order to adjust for important confounding factors.  In particular, the individual medical records contain key relevant quantitative information that is often not coded into an administrative database.  For example, an administrative database like that used by Singh et al. may include a qualitative diagnosis of obesity rather than a quantitative estimate of BMI, as well as a qualitative diagnosis of alcohol abuse rather than a quantitative estimate of alcohol consumption. Similarly, important quantitative information about glycemic control (HbA1C and frequency of hypoglycemia) is not included in Singh’s study. 

Such quantitative information is extremely important in the delicate process of adjusting crude statistical results for confounding clinical factors.  Also of concern is that Singh’s statistical analysis did not adjust for use of anti-diabetic medications other than metformin nor for duration and severity of diabetes.

Finally, clinical application of these findings would require an assessment not only of hazards of a particular treatment paradigm but also the potential benefits of such a program. Estimation of risk/benefit for one treatment protocol can then be compared with risk/benefit for alternatives in order to select appropriate treatment for each individual patient.

The Endocrine Society believes that patients should be made aware of this potential side effect of incretins and the symptoms of pancreatitis.  In addition, we recommend that diabetes care providers consider this possible adverse effect as they balance risk and benefit of particular treatment paradigms, especially in patients with other risk factors for pancreatitis.

The Endocrine Society encourages patients with concerns about this report or about their diabetes treatment to contact their diabetes care provider. Many classes of medications are available that, when combined with healthy eating and physical activity, help achieve and maintain glucose control in type 2 diabetes.

In addition, The Endocrine Society discourages patients with diabetes from stopping medications on their own, without consulting their health care provider, since this can lead to higher levels of blood glucose that may cause serious short-term health problems and, if prolonged, could increase the risk of long term diabetes-related complications.

The Society’s full statement can be accessed online here.

 

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Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 16,000 scientists, physicians, educators, nurses and students in more than 100 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Md. To learn more about the Society, and the field of endocrinology, visit our web site at www.endo-society.org.