GLP-1 and GLP-1/GIP Incretin Agonists and Related Therapies in Metabolic Obesity: A Narrative Review of Pivotal Trials, Pathophysiological Foundations, and Practical Management of Complications

Abstract

The rapid adoption of glucagon-like peptide-1 receptor

agonists,

GLP-1/glucose-dependent

insulinotropic

polypeptide coagonists and related incretin-based therapies

has reshaped the management of obesity, type 2 diabetes and

cardiometabolic complications. Nevertheless, widespread

use outside appropriate medical settings has raised concerns

about prescribing by untrained personnel, non-regulated

magnitud absoluta del efecto, eventos adversos

y

products,

inadequate

titration

and

insufficient

gastrointestinal, renal, nutritional and glycemic follow-up.

This narrative review summarizes the pivotal trials and major

real-world evidence supporting current prescriptions of

liraglutide, dulaglutide, semaglutide, tirzepatide and

emerging therapies. A standardized clinical framework is

used across studies: population, intervention, comparator,

primary endpoint, absolute effect size, safety and

applicability. The review also expands the mechanistic

rationale by which weight loss and potentially weight-

independent pharmacologic actions may influence

cardiovascular disease, heart failure with preserved ejection

fraction, chronic kidney disease, obstructive sleep apnea,

osteoarthritis, polycystic ovary syndrome and metabolic

dysfunction-associated steatotic liver disease. Practical

recommendations are provided for hypoglycemia prevention,

dehydration, acute kidney injury, lean mass preservation and

gastrointestinal adverse event management, including

insulin/sulfonylurea

adjustment,

hydration,

protein

prescription and resistance training.