Few classes of molecules have changed metabolic medicine as much as GLP-1 receptor agonists. To understand where we are now, it helps to look back.
The incretin effect
Since the 1960s it has been known that oral glucose triggers more insulin secretion than the same amount given intravenously. The explanation lies in gut hormones called incretins — mainly GIP and GLP-1.
The half-life problem
Native GLP-1 is broken down by the enzyme DPP-4 within minutes. The first solution came from nature: exenatide, derived from a peptide in Gila monster saliva, approved in the US in 2005. Liraglutide (daily) and semaglutide (weekly) followed, using fatty acid chains to bind albumin.
The landmark trials
- STEP-1 (2021): weekly semaglutide 2.4 mg in adults with obesity, with mean weight loss of about 15% at 68 weeks versus about 2% on placebo.
- SURMOUNT-1 (2022): tirzepatide, a dual GIP/GLP-1 agonist, with mean losses of up to about 21% at the highest dose over 72 weeks.
- SELECT (2023): semaglutide reduced major cardiovascular events by about 20% in people with obesity and cardiovascular disease, without diabetes.
Adverse effects and limitations
The most common adverse effects are gastrointestinal (nausea, vomiting, diarrhoea, constipation). Lean mass is lost alongside fat, and weight is often regained after stopping. These are medicines that require medical assessment and follow-up.
In Brazil
Semaglutide and tirzepatide are registered with ANVISA, and since 2025 their sale requires the pharmacy to retain the prescription.
See the technical profiles for semaglutide, tirzepatide and retatrutide.