The class, defined
Weight-loss peptides are short protein chains that mimic or amplify the body's own metabolic hormones to reduce appetite, slow gastric emptying, and improve glycemic control. The category is dominated by glucagon-like peptide-1 (GLP-1) receptor agonists — a class that started as a type-2 diabetes treatment in 2005 and has become the fastest-growing drug class in modern pharmaceutical history. In 2026, seven GLP-1 or GLP-1-related peptides hold FDA approval for weight management, obesity, or type-2 diabetes, and more than a dozen additional compounds are in Phase 2 or Phase 3 trials for the same indications. This hub catalogs every GLP-1 and weight-loss peptide PeptaHub profiles — 20 compounds in total — ordered by clinical evidence tier, not by commercial popularity. Single-agonist GLP-1s are listed first, followed by dual and triple agonists that combine GLP-1 with GIP, glucagon, or amylin receptor activity. Experimental and research-only compounds round out the list. For each peptide, we link directly to the profile page with mechanism, dosing, side effects, and legal-status detail.
How they work
Weight-loss peptides work through three primary mechanisms: direct appetite suppression via central GLP-1 receptor activation in the hypothalamus, delayed gastric emptying that extends satiety after meals, and improved glucose-dependent insulin secretion that stabilizes post-meal blood sugar. Second- and third-generation compounds layer additional receptor targets on top of GLP-1 — GIP for enhanced insulin response, glucagon for increased energy expenditure, and amylin for further appetite control. The result is a progressively steeper weight-loss curve with each generation: semaglutide produces ~15% body-weight reduction at 68 weeks in STEP trials, tirzepatide produces ~22% at 72 weeks in SURMOUNT-1, and retatrutide produces ~24% at 48 weeks in early Phase 2 data.
GLP-1 receptor agonism
Single-agonist GLP-1s (semaglutide, liraglutide, dulaglutide, exenatide, lixisenatide, orforglipron) bind to GLP-1 receptors in the pancreas, hypothalamus, and gastrointestinal tract. Pancreatic binding increases glucose-dependent insulin secretion while suppressing glucagon. Hypothalamic binding reduces appetite. GI binding slows gastric emptying. These three effects compound into meaningful weight loss and glycemic control.
Dual GIP / GLP-1 co-agonism
Tirzepatide, VK2735, and related dual agonists activate both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. GIP amplifies insulin secretion and appears to reduce nausea compared with GLP-1-only compounds — explaining why tirzepatide users report better tolerability alongside greater weight loss. The mechanism is additive, not synergistic.
Triple agonism (GLP-1 + GIP + glucagon)
Retatrutide, survodutide, and mazdutide add glucagon receptor activity to GLP-1 or GLP-1 + GIP co-agonism. Glucagon increases resting energy expenditure — the body burns more calories at rest — producing the steepest weight-loss curve yet observed with a peptide. Triple agonists are still in Phase 3 as of 2026; approval is expected 2027–2028.
Amylin and PYY mechanisms
Cagrilintide and pramlintide target the amylin receptor, slowing gastric emptying through a different pathway than GLP-1. Peptide YY (PYY) suppresses appetite via the arcuate nucleus. CagriSema combines semaglutide with cagrilintide for additive effects; early Phase 3 data show greater weight loss than either compound alone.
The complete list
20 peptides, ordered by clinical evidence tier. Each entry links to the full profile with mechanism, dosing, side effects, and legal-status detail.
Semaglutide
FDA-approved (Wegovy, Ozempic, Rybelsus)The first long-acting GLP-1 agonist approved for chronic weight management. Once-weekly subcutaneous injection (Wegovy/Ozempic) or daily oral (Rybelsus). STEP trials produced ~15% body-weight reduction at 68 weeks. The category anchor — every other GLP-1 is benchmarked against it.
Tirzepatide
FDA-approved (Mounjaro, Zepbound)Dual GLP-1 / GIP receptor agonist approved for T2D (Mounjaro) and chronic weight management (Zepbound). SURMOUNT-1 showed ~22% weight loss at 72 weeks — the largest non-surgical weight loss ever recorded in a pivotal trial. Better nausea tolerability than single-agonist GLP-1s.
Liraglutide
FDA-approved (Saxenda, Victoza)First-generation once-daily GLP-1 agonist. Saxenda for weight management, Victoza for T2D. Largely superseded by weekly semaglutide and tirzepatide but retains a role for patients requiring shorter-acting agents or titration flexibility.
Dulaglutide
FDA-approved (Trulicity)Weekly GLP-1 agonist approved for T2D with cardiovascular outcomes data from the REWIND trial. Weight loss is modest (~3kg) compared with semaglutide or tirzepatide; dulaglutide's strength is its mature CVD dataset rather than its weight-loss curve.
Exenatide
FDA-approved (Byetta, Bydureon)The first FDA-approved GLP-1 agonist (2005), derived from Gila monster saliva. Twice-daily (Byetta) or weekly (Bydureon) formulations. Largely obsolete for new prescriptions but maintains a small user base and is historically important as the class prototype.
Lixisenatide
FDA-approved (Adlyxin)Short-acting once-daily GLP-1 agonist. Limited commercial uptake in the US due to dosing inconvenience and similar indication overlap with liraglutide. Useful primarily for post-prandial glucose control.
Orforglipron
FDA-approved 2026 (oral non-peptide)Lilly's oral small-molecule GLP-1 agonist approved in 2026 — the first non-peptide GLP-1 that doesn't require fasted dosing or complex bioavailability tricks. ACHIEVE and ATTAIN trials show weight-loss efficacy approaching semaglutide with pill-form convenience.
Retatrutide
Phase 3 (triple GLP-1 / GIP / glucagon)Lilly's triple-receptor agonist activates GLP-1, GIP, and glucagon receptors simultaneously. Early Phase 2 data showed ~24% weight loss at 48 weeks. Phase 3 TRIUMPH trials ongoing; expected FDA submission 2027.
Survodutide
Phase 3 (dual GLP-1 / glucagon)Boehringer Ingelheim / Zealand dual GLP-1 / glucagon agonist in Phase 3 for obesity and MASH (metabolic dysfunction-associated steatohepatitis). Promising liver-fat reduction data alongside conventional weight-loss endpoints.
Mazdutide
Phase 3 (dual GLP-1 / glucagon)Innovent / Lilly dual GLP-1 / glucagon agonist approved in China as IBI362. Phase 3 global trials ongoing. Competes directly with survodutide in the dual-mechanism space and offers the first approved glucagon co-agonist in any major market.
CagriSema
Phase 3 (GLP-1 + amylin)Novo Nordisk's fixed-dose combination of cagrilintide (amylin analog) and semaglutide (GLP-1). REDEFINE trials show weight loss exceeding semaglutide monotherapy. The first amylin-GLP-1 combination in Phase 3.
Cagrilintide
Phase 3 (amylin analog)Long-acting amylin analog studied both alone and as the amylin half of CagriSema. Targets the amylin receptor for satiety and slowed gastric emptying through a different pathway than GLP-1.
VK2735
Phase 2 (dual GLP-1 / GIP)Viking Therapeutics' dual GLP-1 / GIP agonist in Phase 2 for obesity. Early data show competitive efficacy with tirzepatide at comparable doses. Both injectable and oral formulations in parallel development.
Pramlintide
FDA-approved (Symlin)Short-acting synthetic amylin analog approved for type-1 and insulin-dependent type-2 diabetes. Reduces post-meal glucose excursions and provides modest weight benefit. Hypoglycemia risk requires concurrent insulin dose reduction.
AOD-9604
Research-only (GH fragment)Fragment of growth hormone (amino acids 176-191) originally developed for obesity. Failed Phase 2 trials in the 2000s; survives in the research peptide market as an adjunct to more effective compounds. Weak clinical evidence compared with GLP-1s.
Peptide YY
Research (endogenous)Endogenous 36-amino-acid peptide released by the ileum after meals. Suppresses appetite via the arcuate nucleus and is studied as a target for next-generation satiety agents. Not commercially available.
GIP
Research (endogenous incretin)Glucose-dependent insulinotropic polypeptide — the second incretin hormone alongside GLP-1. Native GIP is studied mechanistically; pharmacological use is via dual-agonist peptides like tirzepatide that include GIP activity.
Amylin
Research (endogenous)Pancreatic beta-cell co-hormone released with insulin. Slows gastric emptying and suppresses glucagon. Pharmacological use is via stable analogs (pramlintide, cagrilintide) since native amylin aggregates and is unsuitable for injection.
Nesfatin-1
Early researchHypothalamic peptide fragment of NUCB2. Preclinical and early-phase studies suggest appetite-suppressing effects independent of the leptin pathway. No human efficacy data yet.
Obestatin
Early research (controversial)23-amino-acid peptide encoded by the same gene as ghrelin. Initially reported to oppose ghrelin's appetite-stimulating effects; subsequent studies have been inconsistent. Scientific consensus on its physiological role remains unsettled.
Compared at a glance
The 20 GLP-1 and weight-loss peptides in PeptaHub's directory span a 20-year evolution from first-generation twice-daily injectables to 2026's oral non-peptide agonists and triple-receptor Phase 3 candidates. The table below orders them by FDA status (approved first), then by clinical development stage. The takeaway line at the bottom names which compound currently produces the greatest weight-loss response — that's a matter of trial data, not commercial promotion.
| Peptide | Mechanism | Primary use | FDA status | Route | Half-life |
|---|---|---|---|---|---|
| Semaglutide | GLP-1 | T2D / obesity | Approved | SC weekly / oral daily | ~7 days |
| Tirzepatide | GLP-1 + GIP | T2D / obesity | Approved | SC weekly | ~5 days |
| Liraglutide | GLP-1 | T2D / obesity | Approved | SC daily | ~13 hours |
| Dulaglutide | GLP-1 | T2D (CVD) | Approved | SC weekly | ~5 days |
| Orforglipron | GLP-1 (oral) | T2D / obesity | Approved (2026) | Oral daily | ~29–49 hours |
| Retatrutide | GLP-1 + GIP + glucagon | Obesity | Phase 3 | SC weekly | ~6 days |
| Survodutide | GLP-1 + glucagon | Obesity / MASH | Phase 3 | SC weekly | ~6 days |
| CagriSema | GLP-1 + amylin | Obesity | Phase 3 | SC weekly | ~7 days |
| VK2735 | GLP-1 + GIP | Obesity | Phase 2 | SC / oral | ~6 days |
| AOD-9604 | GH fragment | Obesity (failed) | Research | SC | ~0.5 hours |
As of 2026, tirzepatide produces the greatest weight-loss response among FDA-approved options (~22% body weight at 72 weeks). Retatrutide — still in Phase 3 — has produced ~24% at 48 weeks in early data and will likely replace tirzepatide as the efficacy leader upon approval, with CagriSema and survodutide competing in the dual-mechanism space. Semaglutide remains the most-studied option with the deepest cardiovascular outcomes dataset; orforglipron is the first oral-pill option approaching injectable efficacy.
Safety, side effects & legal status
GLP-1 receptor agonists share a common side-effect profile: nausea, vomiting, constipation, and diarrhea are the most frequent complaints, typically worst during dose escalation and improving over 4–8 weeks. Rare but serious risks include pancreatitis, gallbladder disease, medullary thyroid cancer (animal-model signal; human risk is unclear but contraindicates use in patients with personal or family history of MEN2 or MTC), and diabetic retinopathy worsening in patients with pre-existing retinopathy. Gastroparesis — delayed gastric emptying severe enough to impair surgery or aspiration prevention — is a newer emerging concern with long-acting GLP-1s. All FDA-approved GLP-1s require a prescription. Compounded versions from 503A pharmacies exist in a gray area: the FDA's bulk-drug-list rules permit compounding during shortages but enforce aggressively once shortages end. Research-only peptides (AOD-9604, peptide YY, obestatin) are not approved for human use in any jurisdiction and carry unquantified safety risks when acquired from research chemical suppliers. PeptaHub's methodology for assessing legal status is documented at /methodology.
How to think about this class
The evidence stratification on GLP-1 peptides is clearer than for any other peptide category PeptaHub profiles. FDA-approved options have peer-reviewed Phase 3 data, years of post-marketing surveillance, and accepted prescribing guidelines. Phase 3 candidates (retatrutide, survodutide, mazdutide, CagriSema) have strong interim data but lack long-term safety follow-up and real-world outcomes. Phase 2 and early-phase compounds (VK2735, nesfatin-1, obestatin) are speculative; users taking them are participating in uncontrolled self-experimentation. The rational approach is to use FDA-approved options when access permits, consider compounded versions during legitimate shortage periods, and defer research-only peptides until they accumulate meaningful human trial data. The weight-loss peptide field is moving fast enough that most users asking 'which is best' today will have a different answer 12 months from now — the right strategy is clinician-supervised, evidence-tiered, and patient about the pipeline.
Frequently asked questions
Every FDA-approved weight-loss peptide as of 2026 includes GLP-1 receptor activity as its primary or one of its primary mechanisms. 'GLP-1 agonist' is the narrower term — it refers specifically to compounds binding the GLP-1 receptor. 'Weight-loss peptide' is the broader category that also includes dual and triple agonists adding GIP, glucagon, or amylin activity on top of GLP-1, plus experimental compounds like PYY, nesfatin-1, and obestatin that target different pathways entirely. In practice, 'GLP-1 agonist' and 'weight-loss peptide' are used interchangeably by most clinicians because the non-GLP-1 options haven't produced meaningful clinical weight loss in humans.
Among FDA-approved options as of 2026, tirzepatide (Zepbound/Mounjaro) produces the greatest weight loss at around 22% of body weight over 72 weeks in SURMOUNT-1. Semaglutide (Wegovy/Ozempic) produces around 15% over 68 weeks in STEP trials. Retatrutide, still in Phase 3 as of 2026, has produced around 24% in Phase 2 data and is expected to replace tirzepatide as the efficacy leader upon approval (expected 2027–2028). Individual responses vary widely; body-weight reduction is dose-dependent and strongly influenced by diet and exercise adherence alongside the medication.
Compounded GLP-1s from 503A pharmacies are legal when FDA-approved brand-name versions are officially on the FDA drug shortage list. When a shortage ends, compounding is no longer permitted and FDA enforcement begins. Safety is a separate question: compounded GLP-1s bypass the brand manufacturer's sterility, potency, and impurity controls. The FDA has issued warnings about adverse events from compounded semaglutide and tirzepatide, including dosing errors (compounders sometimes use different units than the brand products). Peptides sold as 'research-only' from gray-market vendors are not compounded medications — they're unregulated chemicals and should not be injected into humans.
The most common side effects are gastrointestinal: nausea (30–50% of users), vomiting, diarrhea, and constipation. These are typically worst during dose escalation and improve over 4–8 weeks as tolerance develops. Less common but serious risks include pancreatitis, gallbladder disease, diabetic retinopathy worsening (in patients with pre-existing retinopathy), and gastroparesis severe enough to complicate surgery. GLP-1s carry a boxed warning for medullary thyroid carcinoma based on rodent data; they are contraindicated in patients with personal or family history of MEN2 or medullary thyroid cancer. Low-glucose events (hypoglycemia) are uncommon as monotherapy but increase when GLP-1s are combined with insulin or sulfonylureas.
Yes, but less well than when combined with lifestyle modification. All major GLP-1 trials (STEP, SURMOUNT, REDEFINE) pair the medication with a reduced-calorie diet and increased physical activity — the quoted weight-loss numbers (15% for semaglutide, 22% for tirzepatide) are combined diet-plus-medication outcomes, not medication alone. That said, real-world data show meaningful weight loss even in users who don't follow a structured diet, because GLP-1s suppress appetite directly. The best outcomes combine the medication's appetite-suppressing effect with a protein-forward diet and resistance training to preserve lean mass during weight loss.
Current FDA labeling and clinical practice treat GLP-1s as chronic medications for obesity, similar to how blood pressure or cholesterol medications are treated as chronic therapies. Stopping a GLP-1 typically results in weight regain — the STEP-4 trial showed users who stopped semaglutide regained about two-thirds of their lost weight within one year. The emerging consensus among obesity medicine specialists is that indefinite use is appropriate for most users achieving their weight goals. Some users taper to a lower maintenance dose rather than stopping outright.
Appetite returns to pre-treatment levels within days to weeks. Weight regain follows gradually, typically averaging two-thirds of lost weight within 12 months per STEP-4 trial data. Cardiovascular risk reduction benefits may persist longer than weight effects, though long-term discontinuation data are still accumulating. The practical takeaway: users who cannot commit to indefinite therapy should set realistic expectations about maintaining results, pair the medication with aggressive lifestyle change, and discuss maintenance dosing with their prescriber before stopping abruptly.
Sources & further reading
External citations underpinning this page. PeptaHub's full sourcing methodology is documented at /methodology — every claim on this page traces back to one of these references or a linked profile.
- GLP-1 Receptor Agonists — review — NEJM
- The expanding landscape of GLP-1 medicines — Nature Medicine
- Glucagon-Like Peptide-1 Receptor Agonists — NCBI StatPearls
- Postmarket Drug Safety Information for Patients and Providers — FDA
- GLP-1 Agonists — drug class reference — Cleveland Clinic
See also: glossary, FAQ, about PeptaHub.