Welcome reassurance about GLP-1 drugs--but they are still young and not fully grown.

Abstract

An excellent article in this issue of Diabetes Care by Yu et al. (1) provides reassurance about the safety of therapies related to GLP-1. This is welcome because of the current uncertainty and anxiety about the use of these agents, which appear very promising yet not without potential risks. To understand the study’s relevance at this stage of development of these agents, consider the process of development of new therapies in general. Like people, therapeutic agents come in families with individual members and a typical life history. A new class of drugs begins as a pathophysiological insight, a gleam in a scientist’s eye. A new drug’s childhood consists of testing in animal (preclinical) studies and small human (phase 1 and 2) studies. Moving into larger clinical studies (phase 3), an adolescent drug must show consistent therapeutic effects and a lack of alarming side effects over 6 to 12 months of use in a broader population of people. Good results can lead to approval for clinical practice after which further (phase 4) studies and observation of clinical experience may explore specific clinical indications and safety during more prolonged use. Because drugs are, by necessity, launched when young and without long-term experience, there can be distressing surprises that lead to later restriction of usage. Full understanding of any drug’s best uses requires years of experience after its introduction. The family of antidiabetes agents based on the actions of GLP-1 emerged from studies of this hormone that began just over 20 years ago (2,3). About 10 years ago, drugs designed to exploit the metabolic and weight-regulating effects of the native hormone entered clinical evaluation. The first were peptides capable of activating GLP-1 receptors (GLP-1 receptor agonists, or GLP-1RAs) (4–7). These peptide drugs significantly improve glucose control and favor weight …