A Comprehensive Review on the Pharmacokinetics and Drug−Drug Interactions of Approved GLP-1 Receptor Agonists and a Dual GLP-1/GIP Receptor Agonist DOI Creative Commons
Jee Sun Min,

Seong Jun Jo,

Sangyoung Lee

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 3509 - 3537

Published: April 1, 2025

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are peptide-derived analogs that were initially investigated to treat type 2 diabetes. Recently, a drug targeting the receptors of both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) (tirzepatide) has been introduced market, its indications have expanded include treating obesity. Here, we review pharmacokinetics, pharmacokinetic drug-drug interactions (DDIs), modeling approaches four currently available RAs (exenatide, liraglutide, dulaglutide, semaglutide) tirzepatide. To address extremely short half-life (2 min) native human GLP-1, structural modifications applied dual GLP-1/GIP RA. These amino acid sequence substitutions, fatty conjugation using linker, fusion with albumin or IgG fragment crystallizable (Fc) region, resulting in minimal metabolism renal excretion. Due their diverse structures, profiles vary, prolonged may be associated an increased risk adverse events. Clinically significant drug-metabolizing enzyme- transporter-mediated DDIs yet reported. Mechanism-of-action-mediated limited those involving delayed gastric emptying, most studies found them clinically insignificant. However, changes exposure observed for oral contraceptives levothyroxine following administration tirzepatide semaglutide, respectively, indicating need close monitoring these instances. Thirty models developed predict pharmacokinetics physiologically based can useful assessing mechanism-of-action-mediated DDIs. Alterations volume distribution clearance from other mechanisms action (eg, reduced fat mass, cytochrome P450 activity, glomerular filtration rate) key factors determining pharmacokinetics. mediated by remain poorly understood require further investigation ensure safely used concomitant medications.

Language: Английский

Glucagon-like peptide-1 receptor agonists and the eye DOI
David Zhang, Avni P. Finn

Current Opinion in Ophthalmology, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Purpose of review Glucagon-like peptide-1 receptor agonists (GLP-1RA) have gained popularity as an antidiabetic and weight loss agent with protective cardiovascular outcomes, but attention to the potential ocular side effects has grown. This aims consolidate existing evidence on GLP-1RA conditions such diabetic retinopathy (DR), nonarteritic ischemic optic neuropathy (NAION), glaucoma, age-related macular degeneration (AMD), idiopathic intracranial hypertension (IIH), dry eye disease (DED). Recent findings The effect DR is controversial likely linked rapid correction hemoglobin A1c levels. may be associated increased risk NAION, although mechanism remains elusive. Protective been shown against AMD, DED possibly due its anti-inflammatory properties, these medications decrease pressure in IIH. Summary As usage increases, further dedicated safety trials are key determining eye-related complications. Given limited prospective available proven systemic benefits medication, well certain diseases, use should generally not discouraged most patients. Regular ophthalmologic follow up important patients considered at higher adverse events.

Language: Английский

Citations

0
Real-World pharmacovigilance analysis of drug-related conjunctivitis using the FDA adverse event reporting system database DOI Creative Commons
Xiang Li, Yali Sun, Miaomiao Liu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 18, 2025

Language: Английский

Citations

0
A Comprehensive Review on the Pharmacokinetics and Drug−Drug Interactions of Approved GLP-1 Receptor Agonists and a Dual GLP-1/GIP Receptor Agonist DOI Creative Commons
Jee Sun Min,

Seong Jun Jo,

Sangyoung Lee

et al.

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 3509 - 3537

Published: April 1, 2025

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are peptide-derived analogs that were initially investigated to treat type 2 diabetes. Recently, a drug targeting the receptors of both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) (tirzepatide) has been introduced market, its indications have expanded include treating obesity. Here, we review pharmacokinetics, pharmacokinetic drug-drug interactions (DDIs), modeling approaches four currently available RAs (exenatide, liraglutide, dulaglutide, semaglutide) tirzepatide. To address extremely short half-life (2 min) native human GLP-1, structural modifications applied dual GLP-1/GIP RA. These amino acid sequence substitutions, fatty conjugation using linker, fusion with albumin or IgG fragment crystallizable (Fc) region, resulting in minimal metabolism renal excretion. Due their diverse structures, profiles vary, prolonged may be associated an increased risk adverse events. Clinically significant drug-metabolizing enzyme- transporter-mediated DDIs yet reported. Mechanism-of-action-mediated limited those involving delayed gastric emptying, most studies found them clinically insignificant. However, changes exposure observed for oral contraceptives levothyroxine following administration tirzepatide semaglutide, respectively, indicating need close monitoring these instances. Thirty models developed predict pharmacokinetics physiologically based can useful assessing mechanism-of-action-mediated DDIs. Alterations volume distribution clearance from other mechanisms action (eg, reduced fat mass, cytochrome P450 activity, glomerular filtration rate) key factors determining pharmacokinetics. mediated by remain poorly understood require further investigation ensure safely used concomitant medications.

Language: Английский

Citations

0