GLP-1 and metabolic peptides, compared
How the incretin drugs and related metabolic compounds differ: what they target, how strong the evidence is, and the doses used on labels and in trials.
| Compound | Evidence | How it works | Doses in labels or trials | US status |
|---|---|---|---|---|
| Dulaglutide Trulicity, LY2189265 | FDA-approved | Established: dulaglutide activates the GLP-1 receptor. This raises insulin release when blood sugar is high, lowers glucagon and slows stomach emptying. Attaching the GLP-1 analog to a large antibody fragment slows its… | Starts at 0.75 mg once weekly, subcutaneous; may be raised to 1.5 mg after 4 weeks, then in 1.5 mg steps every 4+ weeks up to 4.5 mg once weekly 0.75 mg once weekly, may be raised to a maximum of 1.5 mg once weekly after at least 4 weeks | FDA-approved as Trulicity (Eli Lilly): type 2 diabetes in adults (2014), cardiovascular risk reduction (2020), and children 10 and older… |
| Exenatide exendin-4 (synthetic), Byetta, Bydureon | FDA-approved | Established: exenatide activates the GLP-1 receptor. This boosts insulin release only when blood sugar is high, lowers inappropriately high glucagon, and slows stomach emptying. | 5 mcg subcutaneously twice daily within 60 minutes before morning and evening meals; may increase to 10 mcg twice daily after 1 month 2 mg subcutaneously once every 7 days | FDA-approved (Byetta 2005; Bydureon later); US brands Byetta and Bydureon BCise discontinued October 2024 |
| Glucagon Glucagon Emergency Kit, GlucaGen, Baqsimi (nasal) | FDA-approved | Established: glucagon activates glucagon receptors in the liver, breaking down stored glycogen into glucose and raising blood sugar. It only works if the liver has enough glycogen, so it helps little in starvation,… | 1 mg by subcutaneous, intramuscular or IV injection; may repeat if no response in 15 minutes 0.5 mg, or 20–30 mcg/kg | FDA-approved (first US approval 1960); injectable, ready-to-use and nasal (Baqsimi, 2019) forms |
| Insulin (human insulin and analogs) regular human insulin, Humulin R, insulin lispro | FDA-approved | Established: insulin binds the insulin receptor on muscle, fat and liver cells. This increases glucose uptake into muscle and fat, reduces glucose output by the liver, slows fat and protein breakdown, and promotes… | Individualized — labels give no fixed dose; the prescriber sets and adjusts it by glucose monitoring, metabolic needs, route and treatment goals | FDA-approved: human insulin since 1982 (Humulin), lispro 1996, glargine 2000, once-weekly icodec (Awiqli) March 2026 for adult type 2… |
| L-carnitine (levocarnitine) levocarnitine, carnitine, Carnitor | FDA-approved | Established: carnitine acts as a shuttle that moves long-chain fatty acids across the inner membrane of mitochondria, where they are broken down for energy. When carnitine is missing, as in genetic transporter defects,… | 990 mg two or three times daily by mouth 50–100 mg/kg/day in divided doses, maximum 3 g/day | FDA-approved as levocarnitine (Carnitor tablets 1985; oral solution and injection later) for carnitine deficiency and dialysis-related… |
| Liraglutide Saxenda, Victoza, NN2211 | FDA-approved | Established: activates the GLP-1 receptor, increasing glucose-dependent insulin release, lowering glucagon, slowing stomach emptying, and reducing appetite. The fatty-acid chain binds albumin and extends its action to… | 0.6 mg daily week 1, then weekly increases to 1.2, 1.8, 2.4 mg, reaching 3 mg daily from week 5, subcutaneous 3 mg once daily (adults); pediatric 3 mg daily, may reduce to 2.4 mg if not tolerated. Stop in adults if <4% weight loss at 16 weeks. | FDA-approved as Victoza (type 2 diabetes, 2010) and Saxenda (weight management, 2014; adolescents 12+ in 2020). |
| Lixisenatide Adlyxin, Lyxumia, AVE0010 | FDA-approved | Established: lixisenatide activates the GLP-1 receptor. This raises insulin release when blood sugar is high, lowers glucagon and slows stomach emptying. Because it is cleared quickly (mean terminal half-life about 3… | 10 mcg once daily for 14 days, then 20 mcg once daily, subcutaneous 15 to 60 units once daily, subcutaneous, equal to 5 to 20 mcg lixisenatide; maximum 60 units (60 units insulin glargine + 20 mcg lixisenatide) | FDA-approved for type 2 diabetes in adults: alone as Adlyxin (July 2016) and with insulin glargine as Soliqua 100/33 (November 2016). As… |
| Orforglipron Foundayo, LY3502970 | FDA-approved | Established: activates the GLP-1 receptor like peptide GLP-1 drugs, reducing appetite, slowing stomach emptying, and improving blood sugar control. Because it is a small molecule, it is absorbed as a regular pill… | 0.8 mg once daily, then 2.5 mg, then 5.5 mg, each step at least 30 days; by mouth with or without food May increase to 9, 14.5, or 17.2 mg once daily (max 17.2 mg) at ≥30-day intervals based on response and tolerability | FDA-approved as Foundayo (April 1, 2026) for chronic weight management in adults with obesity, or overweight with a weight-related… |
| Pramlintide Symlin, SymlinPen, pramlintide acetate | FDA-approved | Established: like natural amylin, pramlintide slows stomach emptying, lowers the rise in glucagon after meals (so the liver releases less sugar), and increases fullness, which reduces food intake. | Start 15 mcg subcutaneously before major meals; increase in 15 mcg steps to 30–60 mcg as tolerated Start 60 mcg before major meals; increase to 120 mcg if tolerated | FDA-approved as Symlin (2005) as add-on to mealtime insulin in type 1 and type 2 diabetes |
| Semaglutide Wegovy, Ozempic, Rybelsus | FDA-approved | Established: semaglutide activates the GLP-1 receptor. In the pancreas this boosts insulin release and lowers glucagon when blood sugar is high. In the brain it reduces hunger and food intake, and it slows stomach… | 0.25 mg weekly weeks 1–4, 0.5 mg weeks 5–8, 1 mg weeks 9–12, 1.7 mg weeks 13–16, subcutaneous 2.4 mg (recommended) or 1.7 mg once weekly from week 17; adults may go up to 7.2 mg weekly after at least 4 weeks on 2.4 mg if more weight loss is needed. MASH maintenance 2.4 mg (may reduce to 1.7 mg). | FDA-approved: Ozempic (type 2 diabetes, 2017), Rybelsus (oral, type 2 diabetes, 2019), Wegovy injection (weight management 2021; CV risk… |
| Setmelanotide Imcivree, BIM-22493 | FDA-approved | Established: setmelanotide activates MC4 receptors in the brain, which help control hunger, fullness and energy use. In the approved conditions this signal pathway is broken upstream, and the drug restores it. It is… | 2 mg subcutaneously once daily for 2 weeks, then 3 mg once daily (target) 0.5 mg daily, stepped up every 2 weeks to a 3 mg daily target by week 7 | FDA-approved as Imcivree (2020) for POMC/PCSK1/LEPR deficiency and Bardet-Biedl syndrome (age 2+), and acquired hypothalamic obesity (age… |
| Tirzepatide Zepbound, Mounjaro, LY3298176 | FDA-approved | Established: tirzepatide activates both the GIP and GLP-1 receptors. Together these raise glucose-dependent insulin release, lower glucagon, slow stomach emptying, and reduce appetite and food intake. How much the GIP… | 2.5 mg once weekly for 4 weeks (starter dose only), then 5 mg; increase in 2.5 mg steps after at least 4 weeks on each dose, subcutaneous 5, 10, or 15 mg once weekly for weight management; 10 or 15 mg for sleep apnea; maximum 15 mg weekly | FDA-approved as Mounjaro (type 2 diabetes, 2022) and Zepbound (chronic weight management, 2023; obstructive sleep apnea in adults with… |
| Amycretin Zenagamtide (proposed INN, WHO List 133, 2025), NNC0487-0111 | Late-stage trials | Established in lab studies: amycretin is a single molecule that activates the GLP-1 receptor and the amylin receptors, and also the calcitonin receptor, at very low concentrations in cell tests, with little activity at… | Once weekly, subcutaneous, escalated from 0.3 mg to maintenance doses of 1.25, 5, 20 or 60 mg Single oral doses of 1-25 mg; once-daily oral doses up to 50 mg or 2 x 50 mg for 12 weeks | Not FDA-approved. Investigational; in phase 3 trials since February 2026. |
| Avexitide Exendin (9-39), exendin-(9-39) amide, Ex-9 | Late-stage trials | Established: avexitide binds the GLP-1 receptor without switching it on, so it blocks the body's own GLP-1 from acting. Lab work in 1993 showed this truncated exendin fragment acts as a GLP-1 receptor antagonist on… | 45 mg twice daily and 90 mg once daily, subcutaneous, 14 days each 30 mg twice daily and 60 mg once daily, subcutaneous, 14 days each | Investigational; not FDA-approved. Breakthrough Therapy Designation for post-bariatric hypoglycemia and congenital hyperinsulinism, Orphan… |
| Cagrilintide (and CagriSema) NN9838, CagriSema (cagrilintide + semaglutide), long-acting amylin analog | Late-stage trials | Established in trials: cagrilintide activates amylin and calcitonin receptors, which increases feelings of fullness and slows stomach emptying. Combining it with semaglutide (a GLP-1 agonist) adds two different… | 0.3, 0.6, 1.2, 2.4, or 4.5 mg once weekly, subcutaneous, 26 weeks Cagrilintide 2.4 mg + semaglutide 2.4 mg once weekly, subcutaneous, 68 weeks | Investigational; not FDA-approved. New Drug Application for CagriSema submitted December 2025; FDA review expected in 2026 (no decision… |
| Ecnoglutide XW003, Xianyida (China, type 2 diabetes) | Late-stage trials | Established: ecnoglutide activates the GLP-1 receptor, which lowers blood sugar and promotes fullness. Proposed: it is 'cAMP-biased' — in lab tests it strongly triggered the cAMP signal (EC50 0.018 nM) but did not… | 1.2 mg, 1.8 mg or 2.4 mg once weekly, subcutaneous, vs placebo 0.6 mg or 1.2 mg once weekly vs dulaglutide 1.5 mg once weekly | Not FDA-approved; no US marketing application was found in the sources reviewed. |
| Mazdutide IBI362, LY3305677 | Late-stage trials | Established in trials as a dual GLP-1 and glucagon receptor agonist. GLP-1 action reduces appetite and improves blood sugar; glucagon action is proposed to increase energy use and reduce liver fat. In GLORY-1 people… | 4 mg or 6 mg once weekly, subcutaneous, 48 weeks | Not FDA-approved; investigational in the US. |
| Petrelintide ZP8396 | Late-stage trials | Established class mechanism: amylin is released from pancreatic beta cells together with insulin and acts in the brain as a fullness signal. Petrelintide activates amylin receptors; the companies say this leads to… | Maintenance doses of 1.0, 2.5, 5.0, 7.0 or 9.0 mg once weekly, subcutaneous, reached by stepwise dose escalation (every 4 weeks over up to 16 weeks, per company report) Single subcutaneous doses of 0.04-2.4 mg; one 0.35 mg intravenous dose | Investigational; not FDA-approved. Phase 3 trials started in 2026. |
| Retatrutide LY3437943, triple agonist, GGG agonist | Late-stage trials | Established in trials as a triple agonist of the GIP, GLP-1, and glucagon receptors. GLP-1 and GIP action reduce appetite and improve insulin release. Glucagon receptor action is proposed to raise energy use and liver… | 1, 4, 8, or 12 mg once weekly, subcutaneous (starting doses 2 or 4 mg for higher arms), 48 weeks Start 2 mg, escalate to 4, 9, or 12 mg once weekly, subcutaneous, 80 weeks | Investigational; not FDA-approved. Lilly plans to submit an application in Q1 2027. |
| Survodutide BI 456906 | Late-stage trials | Established in trials as a dual glucagon and GLP-1 receptor agonist. GLP-1 action lowers appetite; glucagon action is proposed to increase energy use and fat burning in the liver. This liver effect is why it is also… | 0.6, 2.4, 3.6, or 4.8 mg once weekly, subcutaneous; 20-week escalation then 26-week maintenance 3.6 mg or 6.0 mg once weekly, subcutaneous, 76 weeks | Investigational; not FDA-approved. No FDA submission timeline found in sources reviewed. |
| Tesofensine NS2330, NS 2330, Tesomet (combination with metoprolol) | Late-stage trials | Established: tesofensine is a triple monoamine reuptake inhibitor. It blocks the pumps that clear dopamine, noradrenaline and serotonin from the gaps between nerve cells, so more of these signals stay active. Proposed:… | 0.25 mg, 0.5 mg or 1.0 mg by mouth once daily, vs placebo 0.125, 0.25, 0.5 or 1.0 mg by mouth once daily | Not FDA-approved; investigational only. |
| VK2735 VK-2735, Oral VK2735 (tablet form) | Late-stage trials | Established class mechanism: VK2735 activates both the GLP-1 receptor and the GIP receptor, two hormone receptors that help control blood sugar, appetite and fullness. In company data cited in the phase 2 paper, it… | 2.5, 5, 10 or 15 mg once weekly, subcutaneous, with dose escalation at the start 0.5 to 10 mg once weekly, subcutaneous, some cohorts escalating weekly | Investigational; not FDA-approved. Phase 3 trials of the injection (VANQUISH) and tablet (SUNRISE) are under way. |
| AOD-9604 AOD9604, Tyr-hGH 177-191, anti-obesity drug 9604 | Early human data | Proposed: the fragment was designed to keep growth hormone's fat-breakdown (lipolytic) effect without its effects on growth or blood sugar. In human studies it did not raise IGF-1 or worsen glucose tolerance,… | 25–400 µg/kg (phase 1) and 25–100 µg/kg (phase 2a) intravenous, single doses 9, 27, or 54 mg oral, single doses or daily for 7 days | Not FDA-approved for any use. |
| Eloralintide LY3841136 | Early human data | Established for the drug class, proposed for this molecule: natural amylin is released with insulin after meals and acts on amylin receptors (the calcitonin receptor paired with RAMP helper proteins) in the brainstem… | 1, 3, 6 or 9 mg once weekly by subcutaneous injection; also step-up arms of 6→9 mg and 3→6→9 mg | Investigational; not FDA-approved (phase 3 trials ongoing as of Oct 2026). |
| O-304 (ATX-304) O304, ATX-304, ATX-304 sodium salt | Early human data | Established in lab studies: O-304 is a 'pan-AMPK' activator, meaning it acts on AMPK complexes in general rather than one subtype. In test-tube work it protected AMPK's activating phosphate from being removed by the… | 1,000 mg per day by mouth, as a suspension | Not FDA-approved; investigational. Human trials so far have been in Europe. |
| Oxyntomodulin OXM, Proglucagon (33-69), Glicentin (33-69) | Early human data | Established: oxyntomodulin activates both the GLP-1 receptor and the glucagon receptor, making it a natural co-agonist. In lab tests it is about 10 to 100 times weaker at each receptor than GLP-1 or glucagon… | 3.0 pmol/kg/min intravenous infusion 3.0 pmol/kg/min intravenous infusion | Not FDA-approved. Native oxyntomodulin has been used only in research studies. |
| Pemvidutide ALT-801, SP-1373 | Early human data | Proposed, based on company and trial descriptions: pemvidutide activates both the GLP-1 receptor and the glucagon receptor in a balanced 1:1 ratio. The glucagon part is meant to act directly on the liver to lower liver… | 1.2 mg or 1.8 mg once weekly, subcutaneous, without dose titration, vs placebo 1.2 mg, 1.8 mg or 2.4 mg once weekly, subcutaneous (2.4 mg reached after a 4-week titration), vs placebo | Investigational; not FDA-approved. Has FDA Breakthrough Therapy designation for MASH (announced January 2026) and Fast Track designation… |
| Peptide YY (PYY 3-36) PYY3-36, PYY(3-36), peptide YY3-36 | Early human data | Established in animals: PYY 3-36 cuts food intake by acting on the Y2 receptor; the effect disappears in mice lacking Y2 receptors. In humans, IV PYY 3-36 lowers appetite and food intake, and in one study it also… | 0.2, 0.4 or 0.8 pmol/kg/min by IV infusion vs saline 200 µg or 600 µg intranasal, three times daily before meals | Not FDA-approved. PYY 3-36 and its analogs are investigational only. |
| Adipotide FTPP, Prohibitin-targeting peptide 1, Prohibitin-TP01 | Preclinical only | Proposed (animal data only): the CKGGRAKDC part binds prohibitin, a protein found on the inner lining of blood vessels in white fat. Once bound, the attached D-(KLAKLAK)2 peptide is thought to enter the cells and… | No human dosing data | Not FDA-approved. Studied under an IND in one Phase 1 trial (NCT01262664), which was terminated in 2019. |
| MOTS-c mitochondrial open reading frame of the 12S rRNA-c, MOTSc, CB4211 (related analog) | Preclinical only | Proposed, mostly from mouse and cell studies: MOTS-c acts mainly on skeletal muscle. It interferes with the folate cycle, which raises the level of a natural molecule (AICAR) that activates AMPK, a cellular energy… | No human dosing data | Not FDA-approved for any use. |
Doses are reported, not recommended. Label doses are started low and increased step by step under a prescriber to limit side effects. See each compound page for the full schedule and sources.