GLP-1–Based Therapy for Diabetes: What You Do Not Know Can Hurt You

  1. Peter C. Butler, MD,
  2. Sarah Dry, MD and
  3. Robert Elashoff, PHD
  1. From the Larry L. Hillblom Islet Research Center, Department of Pathology and Department of Biomathematics, University of California, Los Angeles, Los Angeles, California.
  1. Corresponding author: Peter Butler, pbutler{at}

According to the Oxford Dictionary of Proverbs, the oldest written version of the saying “What you don't know can't hurt you” comes from Petit Palace, written in 1576 by G. Pettie: “So long as I know it not, it hurteth mee not.”

In this issue of Diabetes Care, Drucker et al. (1) conclude that the safety profile of the newly available glucagon-like peptide 1 (GLP-1) class of drugs is favorable in comparison to their benefits as therapy, and the class of drugs might be considered as next in line after metformin for treatment for type 2 diabetes. The purpose of this counterpoint is to suggest such a conclusion is premature. History has taught us that enthusiasm for new classes of drugs, heavily promoted by the pharmaceutical companies that market them, can obscure the caution that should be exercised when the long-term consequences are unknown. Of perhaps greatest concern in the case of the GLP-1–based drugs, including GLP-1 agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, is preliminary evidence to suggest the potential risks of asymptomatic chronic pancreatitis and, with time, pancreatic cancer.

The GLP-1–related drugs arrived in clinical practice with much fanfare and anticipation. As summarized in the article by Drucker et al., it is a class of drugs that has potential benefits in the treatment of type 2 diabetes. The concept of gut-related factors that enhance glucose-mediated insulin secretion, the incretin effect, has been recognized for many years (2). Once it was demonstrated that an intravenous infusion of GLP-1 could decrease blood glucose concentrations in patients with type 2 diabetes, the race was on to exploit the properties of this action. Many millions of dollars have been invested by the pharmaceutical industry in developing products, the first of which are now in clinical practice. Many millions of dollars …

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