GLP-1 agonists for people living with HIV and obesity, is there a potential?

• Published in: HIV medicine 2023-10, Vol.24 (10), p.1029-1034
• Main Authors: Zino, L, Tack, C J, Richel, O, Burger, D M
• Format: Article
• Language: English
• Subjects: Agonists; Antiviral agents; Clinical trials; Diabetes mellitus; Diabetes Mellitus, Type 2; Drug interaction; Drugs; Glucagon; Glucagon-Like Peptide 1 - therapeutic use; Heart rate; HIV; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Hypoglycemic Agents - adverse effects; Liraglutide - adverse effects; Obesity; Obesity - complications; Obesity - drug therapy; Pharmacology; Prolongation; Protease inhibitors; Proteinase inhibitors; Risk factors; Safety; Weight control; Weight Loss
• ISSN: 1464-2662; 1468-1293; 1468-1293
• DOI: 10.1111/hiv.13521

Obesity trends and metabolic dysregulation are rising in people living with HIV using antiretrovirals (ARVs). Underlying causes and preventive strategies are being investigated. Two glucagon like-peptide 1 (GLP-1) agonists, liraglutide and semaglutide, were formerly approved as glucose-lowering drugs and have been recently approved for long-term weight loss in people with obesity. Due to the lack of therapeutic guidelines or clinical trials in people with HIV, we discuss the potential benefits, safety aspects and pharmacological considerations of prescribing liraglutide and semaglutide in people with HIV. Clinical experience is limited to two clinical cases of diabetic people with HIV using liraglutide after which a successful weight loss and glycaemic control were observed. None of the adverse events associated with liraglutide and semaglutide usage indicate an additional risk for people with HIV. Extra caution showed be warranted when initiating GLP-1 agonist therapy in people with HIV taking protease inhibitors who have pre-existing risk factors for heart rate variability to reduce the incidence of RP interval prolongation. GLP-1 agonists are metabolized by endopeptidases, and thus do not generate major drug-drug interactions with most drugs, including ARVs. GLP-s agonists are known to inhibit gastric acid secretion, which warrants caution and close monitoring when combined with atazanavir and oral rilpivirine, two ARVs that require low gastric pH for an optimal absorption. Theoretical considerations and a few available clinical observations support semaglutide and liraglutide prescription in people with HIV, with, thus far, no indications of concern regarding efficacy, safety or pharmacological interactions with ARVs.