Spotlight on GLP-1 receptor agonists
Cost and access issues were the focus of multiple recent articles about glucagon-like peptide-1 (GLP-1) and dual glucose-dependent insulinotropic polypeptide receptor agonists, while the latest research on these drug classes highlighted their clinical benefits.
Glucagon-like peptide-1 (GLP-1) receptor agonists were addressed by recent studies and statements.
On Dec. 2, the American Diabetes Association (ADA) put out a statement on use of compounded GLP-1 or dual glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. The statement notes that shortages of these drugs have led to increased production and marketing of compounded versions, but the ADA does not recommend patients use non-FDA-approved compounded incretin products “due to uncertainty about their content and resulting concerns about safety, quality, and effectiveness.” In case of a shortage, it is preferable to switch to a different FDA-approved medication and then reassess the appropriateness of resuming the original medication when the shortage is resolved, the ADA said. However, the statement does also offer guidance for individuals who are considering using a compounded product, including discussing the idea with their usual health care professional. The statement, published in Diabetes Care, also offers a list of key warning signs that an online pharmacy or distributor of compounded products may be unsafe.
Another article addressed the challenge of how much it would cost to provide GLP-1/GIP receptor agonists to all who could benefit from their weight-management effects. The article, published by Annals of Internal Medicine as an Ideas and Opinions piece on Nov. 26, reviewed the ethics of several possible approaches, including exclusion, tiering, capped reimbursements, formulary reevaluation, subscription model payment, and patent reform. “For smaller plans, formulary reevaluation is the most ethical path forward. For governments and larger plans that can leverage market power, alternative payment models and regulatory reforms should be actively pursued,” it concluded.
A Viewpoint article, published by JAMA on Nov. 13, discussed the problem of frequent discontinuation of GLP-1 receptor agonists, noting that it's particularly problematic for this medication class given the “high cost, large treatment-eligible population (approximately 140 million US adults), and potential for worsening cardiovascular risk after discontinuation.” The article discusses the issues of side effects, costs, coverage, and shortages and calls for qualitative and quantitative research to understand and combat treatment discontinuation. “Both equitable initiation and persistence are necessary to optimize the societal return on the massive economic investment in GLP-1 [receptor agonist] therapies,” the article concludes.
Finally, in the latest research on the subject, a meta-analysis of 11 trials with 85,373 patients, published by The Lancet Diabetes & Endocrinology on Nov. 25, found evidence that GLP-1 receptor agonists significantly reduce clinically important kidney events, kidney failure, and cardiovascular events, even in patients without diabetes. An accompanying editorial noted that such data will only increase demand for the drugs and called on those in power to “decide on a reasonable, fair value for the cost of these treatments, especially when used at scale and over the long term, and find ways to provide equitable access to individuals, with the most potential for health improvement.” An industry-funded trial, published by the New England Journal of Medicine on Nov. 13, found that, for patients with obesity and prediabetes, three years of tirzepatide, a GLP-1/GIP receptor agonist, substantially lowered weight and risk of progression to type 2 diabetes compared to placebo.