GLP-1 overview — five molecules, the pivotal RCTs, and the Brazilian regulatory frame

Quick answer

The GLP-1 class in 2026 covers five molecules across two indications (type 2 diabetes and obesity) with four of them holding regulatory approval and one in phase 3. Liraglutide (Victoza for T2D; Saxenda for obesity), semaglutide (Ozempic for T2D; Wegovy for obesity; Rybelsus oral for T2D), and tirzepatide (Mounjaro for T2D and now obesity) are the registered products. Retatrutide is the triple GIP/GLP-1/glucagon agonist with phase 2 published (24.2% mean weight loss at 12 mg over 48 weeks) and the TRIUMPH phase 3 program ongoing, with no approval in any country yet. The pivotal phase 3 trials — STEP 1 for semaglutide (-14.9% over 68 weeks), SURMOUNT-1 for tirzepatide (-20.9% at 15 mg over 72 weeks), and SURMOUNT-5 (head-to-head: tirzepatide -20.2% vs semaglutide -13.7%) — define the comparative landscape. SELECT (n=17,604) added cardiovascular benefit for semaglutide 2.4 mg in obesity without diabetes (MACE HR 0.80). The Brazilian regulatory frame in 2026 includes ANVISA Technical Note 200/2025 (technical criteria for peptide APIs), RDC 973/2025 (mandatory prescription retention since June 23, 2025), and Despatch 97/2025 (semaglutide compounding ban).

Why this guide exists

Search on GLP-1 collides with three very different sources: (a) general media treating all molecules as interchangeable "weight-loss pens"; (b) compounding catalogs still circulating peptide inputs labeled as "research" despite regulatory bans; (c) dense clinical literature and ANVISA acts that separate the class into silos without giving an integrated landscape.

What's missing is editorial synthesis describing, in one read, the full ANVISA approval timeline, the practical impact of regulatory acts of 2025-2026, the pivotal RCTs supporting each indication, and the limits of what is regulatorily legitimate in Brazil today.

This guide is that synthesis. It does not direct doses, recommend choices between molecules, or advise intervention. It describes what exists in indexed literature and ANVISA acts as of April 2026. The canonical Portuguese fact-sheets at /peptideos/liraglutida and /peptideos/retatrutida carry the molecule-level detail.

The five molecules

Liraglutide — first in class

Liraglutide is a daily-injection GLP-1 receptor agonist with extended half-life via fatty acid acylation that prolongs albumin binding. It exists in two registered products in Brazil:

• Victoza — registered by ANVISA in March 2010 for type 2 diabetes in adults, doses 1.2 and 1.8 mg/day. First GLP-1 analog approved in Brazil. Followed EMA registration (2009) and ran in parallel with FDA (2010).
• Saxenda — registered February 29, 2016, for obesity (BMI ≥30 or ≥27 with weight-related comorbidity). Liraglutide 6 mg/mL escalated up to 3.0 mg/day. The regulatory basis was SCALE Obesity and Prediabetes (Pi-Sunyer 2015, NEJM, PMID 26132939) with n=3,731 — 8.4 kg loss vs 2.8 kg placebo over 56 weeks.

Cardiovascular trial: LEADER (Marso 2016, NEJM, PMID 27295427), n=9,340 with T2D and high CV risk, MACE 13.0% vs 14.9% placebo (HR 0.87, p=0.01). Cardiovascular mortality reduced (HR 0.78). The historic CV reference for the class.

Semaglutide — three products, two routes

Semaglutide is a once-weekly GLP-1 receptor agonist (subcutaneous) with structural modifications extending the half-life to ~7 days. It has three registered products in Brazil:

• Ozempic — registered by ANVISA in 2018 for T2D, doses 0.25, 0.5, and 1 mg weekly. Weekly administration vs daily liraglutide was the central pharmacokinetic differential.
• Rybelsus — registered October 2020, oral 3, 7, and 14 mg tablets for T2D. First oral GLP-1 analog, enabled by co-formulation with SNAC (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate), an excipient enabling gastric peptide absorption.
• Wegovy — registered January 2023 for weight management (BMI ≥30 or ≥27 with comorbidity, and adolescents ≥12 with obesity by percentile). Weekly 2.4 mg subcutaneous. Practical pharmacy availability in Brazil came in August 2024, with about 18 months between regulatory approval and effective supply, attributed to global production constraints.

Pivotal obesity RCT: STEP 1 (Wilding 2021, NEJM, PMID 33567185), n=1,961 across 16 countries, 68 weeks. Weight loss −14.9% vs −2.4% placebo — magnitude that repositioned the class above what liraglutide reached in SCALE.

Cardiovascular RCT: SELECT (Lincoff 2023, NEJM, PMID 37952131), n=17,604 with obesity and CV disease without diabetes. MACE 6.5% vs 8.0% placebo (HR 0.80, p<0.001). The first RCT to demonstrate CV benefit in obesity without diabetes.

Tirzepatide — first dual GIP+GLP-1

Tirzepatide (Mounjaro) is a synthetic 39-amino-acid peptide acting as a dual agonist at GIP and GLP-1 receptors. Registered products in Brazil:

• Mounjaro for T2D — registered September 25, 2023, weekly doses 2.5/5/7.5/10/12.5/15 mg. Regulatory basis: SURPASS program, particularly SURPASS-2 (Frías 2021, NEJM, PMID 34170647), n=1,879, demonstrating superiority over semaglutide 1 mg in T2D (HbA1c −2.30 vs −1.86 at 15 mg, all tirzepatide doses superior).
• Mounjaro for obesity/overweight — extension approved June 9, 2025 for obesity or overweight with comorbidity in adults. Regulatory basis: SURMOUNT-1 (Jastreboff 2022, NEJM, PMID 35658024), n=2,539, weight loss −20.9% at 15 mg over 72 weeks; and SURMOUNT-5 (Aronne 2025, NEJM, PMID 40353578), n=751, head-to-head with semaglutide.

Head-to-head SURMOUNT-5 result: tirzepatide (10 or 15 mg) −20.2% vs semaglutide (1.7 or 2.4 mg) −13.7% in obesity without diabetes over 72 weeks (p<0.001). Discontinuation due to GI events: 2.7% (tirzepatide) vs 5.6% (semaglutide). This is the trial defining direct hierarchy between the two molecules in obesity without diabetes in 2026.

Retatrutida — the triple agonist in development

Retatrutide (LY3437943) is a triple GIP/GLP-1/glucagon receptor agonist from Eli Lilly, without regulatory approval in any country as of April 2026.

Phase 2 results: Jastreboff 2023 (NEJM, PMID 37366315), n=338, 48 weeks. Weight loss −24.2% in the 12 mg arm vs −2.1% placebo. The TRIUMPH phase 3 program (TRIUMPH-1 to TRIUMPH-4) is ongoing with over 5,800 participants. Estimated approvals: FDA/EMA 2027-2028, ANVISA 2028-2029. Inputs labeled as retatrutide circulating in international parallel markets since 2023 represent irregular importation without audited chemical characterization.

Approval timeline (Brazil)

Pivotal RCT comparison

Obesity trials

Published head-to-head trials

• STEP 8 (Rubino 2022, JAMA, n=338) — Semaglutide 2.4 mg vs liraglutide 3.0 mg in obesity without diabetes, 68 weeks. Loss −15.8% (semaglutide) vs −6.4% (liraglutide).
• SURPASS-2 (Frías 2021, NEJM, n=1,879) — Tirzepatide 5/10/15 mg vs semaglutide 1 mg in T2D, 40 weeks. HbA1c −2.01/−2.24/−2.30 vs −1.86 — all tirzepatide doses superior.
• SURMOUNT-5 (Aronne 2025, NEJM, n=751) — Tirzepatide (10 or 15 mg) vs semaglutide (1.7 or 2.4 mg) in obesity without diabetes, 72 weeks. Loss −20.2% vs −13.7% (p<0.001). Current direct comparison reference.

Cardiovascular trials

• LEADER (Marso 2016, NEJM, n=9,340) — Liraglutide in T2D with high CV risk. MACE 13.0% vs 14.9% placebo (HR 0.87, p=0.01).
• SELECT (Lincoff 2023, NEJM, n=17,604) — Semaglutide 2.4 mg in obesity with CV disease without diabetes. MACE 6.5% vs 8.0% placebo (HR 0.80, p<0.001). First RCT to demonstrate CV benefit in obesity without diabetes.
• SURPASS-CVOT — Tirzepatide vs dulaglutide in T2D with CV disease. Top-line results disclosed in 2026; indexed publication in process at the date of this guide.

The Brazilian regulatory layer

The regulation of GLP-1 in Brazil rests, in 2026, on three pillars built in 2025-2026, applied on top of decades of standard ANVISA framework for peptide medicines.

Technical Note No. 200/2025

ANVISA's Technical Note No. 200/2025/SEI/GIMED/GGFIS/DIRE4/ANVISA, published in 2025, is the central regulatory document for compounded peptides in Brazil. It defines minimum quality assays for imported peptide APIs that compounding pharmacies must meet:

• HPLC/UV identification — confirms molecular identity of received API.
• Peptide mapping — reference standard comparison via enzymatic digestion and chromatographic separation, ensuring expected amino acid sequence.
• Assay by validated method — active principle quantification per pharmacopeial or validated method.
• Impurity analysis — including truncated peptides, dimers, and degradation products.
• Sterility and endotoxins — specific requirement for injectable forms, per USP <71> and <85>.
• Origin from supplier with audited chain — restricted to authorized distributors.

In practice, few compounding pharmacies meet all these criteria with the technical depth required. The Technical Note has become the central reference in ANVISA enforcement actions throughout 2025-2026.

RDC No. 973/2025 — prescription retention

In force since June 23, 2025, the ANVISA Resolution No. 973/2025 established new criteria for prescription, dispensing, control, packaging, and labeling of GLP-1 receptor agonist medicines.

What changed in practice:

• Two-copy prescription — physician issues prescription in two copies; one stays at the pharmacy, the other with the patient.
• 90-day validity — prescription expires after this period.
• SNGPC registration — National System for Management of Controlled Products tracks each box dispensed, similar to medicines under retention (psychotropics, antimicrobials).
• Applies to the entire industrialized class — Victoza, Saxenda, Ozempic, Wegovy, Rybelsus, and Mounjaro are subject to the RDC.

The RDC was an institutional response to growth of off-label use, increase in adverse events reported in pharmacovigilance, and reaction to expansion into the obesity market.

Despatch 97/2025 — semaglutide compounding ban

In August 2025, by Despatch 97/2025, ANVISA expressly prohibited magistral compounding of semaglutide in all its commercial formulations (Ozempic, Wegovy, and Rybelsus). The basis: availability of registered industrialized product, sanitary risk, large-scale compounding in pharmacies with very different technical capacity, and discrepancy between imported volume and legitimate market.

ANVISA reported that imports of peptide APIs in the second half of 2025 exceeded 100 kg — quantity sufficient for approximately 20 million doses, disproportionate to the legitimate compounding market and signaling direct-to-consumer use without valid prescription at scale.

Tirzepatide compounding is not categorically banned in 2026, but is under rigorous monitoring. With Mounjaro for obesity registered (06/2025), the regulatory environment applied to tirzepatide tends to converge with that of semaglutide. For retatrutide (no registration in any country), magistral compounding is not endorsed by ANVISA — the molecule has no API registration in any sanitary reference country.

2026 enforcement actions

In an institutional communication in April 2026, ANVISA reported executive actions concentrated in the first quarter of the year:

• 11 inspections in compounding pharmacies and importers
• 8 facility shutdowns for technical problems and lack of quality control
• 10 prohibition actions on importation, commerce, and use of irregular GLP-1 products since January 2026

The aggregated communication did not nominally detail the 8 shutdowns or the 10 prohibition actions with specific portaria numbers.

Evidence hierarchy by compound

Most robust — liraglutide. Over 15 years of post-marketing pharmacovigilance (Victoza since 2010, Saxenda since 2014/2016). Dedicated cardiovascular trial (LEADER). Broad SCALE base in obesity. Consolidated adverse event profile.

Robust and growing — semaglutide. Complete STEP program in obesity (STEP 1-8), SUSTAIN program in T2D, PIONEER program for the oral version, and SELECT as cardiovascular trial in obesity without diabetes with median follow-up of 39.8 months. Post-marketing pharmacovigilance since 2018 (Ozempic) and 2023 (Wegovy).

Consolidating — tirzepatide. SURPASS program in T2D, SURMOUNT program in obesity, head-to-head SURMOUNT-5 vs semaglutide. Post-marketing pharmacovigilance since 2022 (FDA) and 2023 (ANVISA).

Initial — retatrutide. Phase 2 published (Jastreboff 2023). TRIUMPH phase 3 program ongoing, no peer-reviewed publication of pivotal trials as of April 2026.

The hierarchy does not mean one molecule is "better" than another — it means published evidence base and post-marketing pharmacovigilance duration are unequal, with direct implication for clinical decision in specific populations (older adults, people with CV disease, prolonged use).

What we know

1. Liraglutide, semaglutide, and tirzepatide produce mean weight losses of 8-21% in obesity over 56-72 weeks, with magnitude scaling by molecule and dose.
2. Semaglutide 2.4 mg reduces MACE by 20% in adults with obesity and CV disease without diabetes (SELECT, n=17,604).
3. Tirzepatide is superior to semaglutide in head-to-head obesity (SURMOUNT-5: −20.2% vs −13.7%) and T2D (SURPASS-2: HbA1c −2.30 vs −1.86 at 15 mg).
4. Retatrutide phase 2 produced −24.2% weight loss at 12 mg over 48 weeks, with phase 3 results pending.
5. ANVISA banned magistral semaglutide compounding in August 2025; prescription retention is mandatory class-wide since June 23, 2025.
6. GLP-1 weight regain after discontinuation is documented (STEP 4, Rubino 2021).

What we don't yet know

• Head-to-head between tirzepatide and retatrutide.
• Head-to-head between semaglutide and retatrutide.
• Published phase 3 trials of retatrutide — TRIUMPH-1 to TRIUMPH-4 in progress, top-line readouts expected from 2026, peer-reviewed publications expected in 2027.
• Long-term cardiovascular outcomes of retatrutide and tirzepatide in obesity without diabetes (ongoing SURPASS-CVOT for tirzepatide; TRIUMPH-3 for retatrutide).
• Optimal long-term maintenance strategy after initial weight-loss phase.
• Pediatric and adolescent long-term safety beyond the indications already approved.

When it makes sense to ask the endocrinologist

The choice to start GLP-1 therapy — and which molecule — is an individualized clinical decision depending on variables this page cannot determine. pephealth does not direct intervention.

For someone researching the class from media, forum, or commercial catalog reading, bringing concrete questions to the endocrinology visit makes a difference:

• What is the proposed indication — type 2 diabetes, obesity, overweight with comorbidity, CV prevention — and which specific RCT supports the proposal for my case?
• What is the proposed molecule, and why over alternatives? Is there a published head-to-head supporting the choice?
• What is the product — registered industrialized (Victoza, Saxenda, Ozempic, Wegovy, Rybelsus, Mounjaro) or compounded? In a pharmacy with prescription retention per RDC 973/2025?
• What is the monitoring plan for efficacy (weight, A1c, metabolic parameters) and safety (GI, biliary, pancreatic events)?
• What is the strategy for discontinuation or long-term maintenance, given that weight regain after interruption is described in literature (STEP 4, Rubino 2021)?
• What is the position on cost and coverage — the registered industrialized product has high price and limited SUS coverage for obesity indication.

Editorial closing

The GLP-1 class is, in 2026, the most robust and most scrutinized case of peptide pharmacology in obesity in Brazil. Published phase 3 evidence covers five molecules across different regulatory statuses. SURMOUNT-5 (2025) is the direct comparison reference. SELECT (2023) is the CV base in obesity without diabetes. LEADER (2016) is the historical CV base in T2D.

ANVISA regulation, built in layers since 2010, reached its most restrictive phase in 2025-2026 — Technical Note 200/2025 (technical criteria for peptide APIs), RDC 973/2025 (prescription retention since June 23, 2025), Despatch 97/2025 (semaglutide compounding ban), and 2026 executive actions with 8 facility shutdowns and 10 importation prohibitions. The current regulatory environment positions registered industrialized product as the only legitimate route for GLP-1 intervention in Brazil for most indications.

pephealth neither recommends nor discourages any molecule in the class. The function of this guide is to describe, with transparency about what exists in indexed literature and ANVISA acts of 2026: what is approved, what is banned, what is in development, and what supports each regulatory decision.