Emerging and Off-Label Uses Of Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA) and Dual GIP/GLP1-RAs

Glucagon-like peptide-1 receptor agonists (GLP1-RAs) and the glucagon-dependent insulinotropic polypeptide (GIP)/GLP1-RA are approved for type 2 diabetes (T2D) and obesity given their profound impact on glycemic weight management. Additional indications include reducing cardiovascular disease risk and progression of chronic kidney disease (CKD) in T2D as well as obstructive sleep apnea in patients with obesity. These enhanced effects are likely due to their pleiotropic effects, leading to decreased inflammation and other benefits. This review explored emerging evidence for uses of GLP1-RAs and GIP/GLP1-RA that have been researched but not yet approved. Clinicians may use this information to guide treatment decisions.

PubMed and Embase literature searches were conducted using Medical Subject Heading terms. Studies referencing GLP1-RAs and GIP/GLP1-RA were included if they were published in approximately the last decade, included adults, and were either a randomized controlled trial, meta-analysis, or observational study. Of 319 articles reviewed, 27 met inclusion criteria.

Initial positive impacts have been noted for the following conditions: liver disease/liver transplant, CKD/kidney transplant, Alzheimer's disease, Parkinson's disease, substance use disorders, osteoarthritis, rheumatoid arthritis, psoriasis, COVID-19 virus, asthma, chronic obstructive pulmonary disorder, polycystic ovarian syndrome, and short bowel syndrome.

Large randomized controlled trials may lead to approvals of these conditions and are encouraged. Safety and adverse effects of these medications must be assessed when initiating or modifying doses.

GLP1-RAs and GIP/GLP1-RA have demonstrated early benefits to several conditions beyond their current approved indications. Clinicians can use this information to determine treatment options for patients, particularly in those with T2D, cardiovascular disease, and/or obesity.