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GLP-1 / Metabolic

Orforglipron Guide & Tableau de Dose

An oral small-molecule GLP-1 agonist studied for weight and glycemia.

Également appeléLY3502970
Voiesubcutaneous
Orforglipron — Tableau de dose
Chaque ligne citée
ObjectifDoseFréquenceDuréePreuveSource
Obesity treatment (weight reduction) - Phase 3 6 mg 1x/day 72 weeks Clinical PMID 40960239
Obesity treatment (weight reduction) - Phase 3 12 mg 1x/day 72 weeks Clinical PMID 40960239
Obesity treatment (weight reduction) - Phase 3 36 mg 1x/day 72 weeks Clinical PMID 40960239
Type 2 diabetes glycemic control - Phase 3 3 mg 1x/day 40 weeks Clinical PMID 40544435
Type 2 diabetes glycemic control - Phase 3 12 mg 1x/day 40 weeks Clinical PMID 40544435
Type 2 diabetes glycemic control - Phase 3 36 mg 1x/day 40 weeks Clinical PMID 40544435
Safety/tolerability/PK - Phase 1 single ascending dose 0.3–6 mg single dose per trial Clinical PMID 37344954
Safety/tolerability/PK - Phase 1 multiple ascending dose 2–24 mg 1x/day 4 weeks Clinical PMID 37344954
Obesity treatment (weight reduction) - Phase 2 12–45 mg 1x/day 36 weeks Clinical PMID 37351564
À des fins de recherche et d'éducation uniquement. Pas un avis médical.

What is Orforglipron?

Orforglipron — also called LY3502970 — is a first-of-its-kind research compound. It is a small-molecule, non-peptide GLP-1 receptor agonist designed to be taken by mouth, once a day, as a simple pill or capsule. That might sound routine, but it is actually a big deal in this field. Most GLP-1 drugs you have heard about (think semaglutide or liraglutide) are peptides — large, fragile molecules that must be injected because stomach acid would destroy them. Orforglipron is chemically different: it is small and stable enough to survive digestion and be absorbed through the gut.[6] Researchers are investigating it for two main areas: weight reduction in people with obesity and blood-sugar control in people with type 2 diabetes.[5][2] It is currently a research compound; it is not approved for medical use.

How Orforglipron Works

Think of the GLP-1 receptor like a doorbell on certain cells in your body — in the gut, brain, and pancreas. Normally, a hormone your gut releases after eating (called GLP-1) rings that doorbell. The signal tells the pancreas to release insulin, tells the brain you are full, and slows down how fast your stomach empties food into your intestine. Injectable GLP-1 drugs work by mimicking that hormone. Orforglipron does the exact same job — it rings the same doorbell — but it is a tiny synthetic molecule rather than a peptide copy of the hormone.[6] Because it is small, it can be swallowed. And because it has a long half-life (roughly 25–68 hours in early studies), it stays active in the body long enough for once-daily dosing without any special food or water restrictions.[1] That is a key practical advantage over the oral peptide GLP-1 drug semaglutide, which requires strict fasting rules before and after each dose.

What the Research Shows

Phase 1 — Safety and Early Signals

The earliest human studies tested single doses (0.3–6 mg) and then four weeks of daily dosing (2–24 mg) in healthy adults. Orforglipron was generally well tolerated. The most common side effects were gastrointestinal (nausea, etc.) — the same pattern seen with injectable GLP-1 drugs. After just four weeks of daily dosing, participants lost up to 5.4 kg compared with 2.4 kg in the placebo group.[1] A separate Phase 1 study in people with type 2 diabetes found that after 12 weeks, HbA1c (a measure of average blood sugar) dropped by 1.5%–1.8% across orforglipron doses versus only 0.4% with placebo, and body weight fell by up to 5.8 kg versus a slight gain with placebo.[3]

Phase 2 — Obesity (GZGI Trial)

A Phase 2 randomized trial enrolled 272 adults with obesity (no diabetes) and assigned them to orforglipron at doses of 12, 24, 36, or 45 mg once daily, or placebo, for 36 weeks. By week 36, average body weight fell by 9.4%–14.7% in the orforglipron groups versus 2.3% with placebo. Between 46% and 75% of participants on orforglipron lost at least 10% of their body weight by week 36.[5] Those are numbers comparable to injectable GLP-1 therapies.

Phase 3 — Obesity (ATTAIN-1 Trial)

The large ATTAIN-1 Phase 3 trial randomized over 3,100 adults with obesity (but no diabetes) to orforglipron at 6 mg, 12 mg, or 36 mg once daily, or placebo, for 72 weeks. Body weight fell by 7.5%, 8.4%, and 11.2% respectively, versus 2.1% with placebo — all statistically significant. Over half (54.6%) of participants in the 36 mg group lost 10% or more of their body weight. Beyond weight, the 36 mg group also showed meaningful improvements in waist circumference, systolic blood pressure, triglycerides, and non-HDL cholesterol. Gastrointestinal side effects were the most common adverse events and were mostly mild to moderate.[4]

Phase 3 — Type 2 Diabetes (ACHIEVE-1 Trial)

The ACHIEVE-1 trial enrolled 559 adults with early type 2 diabetes (managed only by diet and exercise) and randomized them to 3 mg, 12 mg, or 36 mg of orforglipron once daily, or placebo, for 40 weeks. All three doses significantly outperformed placebo on the primary goal: lowering HbA1c. Average HbA1c dropped by 1.24–1.48 percentage points with orforglipron versus 0.41 points with placebo, landing final average HbA1c values in the 6.5%–6.7% range — close to or within the normal range. Body weight also fell, by 4.5%–7.6% depending on dose versus 1.7% with placebo. No episodes of severe hypoglycemia (dangerous low blood sugar) were reported.[2]

What Orforglipron Is Being Studied For

  • Weight reduction in adults with obesity — multiple Phase 2 and Phase 3 trials[5][4]
  • Glycemic (blood sugar) control in type 2 diabetes — Phase 1 through Phase 3 trials[3][2]
  • Pharmacokinetics and tolerability — understanding how the drug moves through the body and what doses are safe[1]

How Orforglipron Is Dosed in Research

Research doses have ranged from sub-milligram single doses in the earliest safety work all the way up to 45 mg per day in Phase 2. Phase 3 trials have focused on once-daily oral doses of 3 mg, 6 mg, 12 mg, and 36 mg, delivered over periods of 40 to 72 weeks depending on the indication.[2][4] For the full breakdown by study phase and indication, see the dosage chart on this page. To explore how doses scale or compare across studies, use the calculator also found on this page. Remember: these are research reference figures only and do not constitute medical dosing advice.

Mixing and Storing Orforglipron

Orforglipron is a small-molecule oral compound, which means it does not require the reconstitution steps needed for peptide-based research compounds. In clinical trials it has been administered as a standard oral formulation — no mixing with bacteriostatic water, no syringes, no vials. For research purposes, follow the specific storage and handling instructions provided by your supplier or the relevant study protocol. In general, small-molecule compounds like this are stored at controlled room temperature away from light and moisture unless the supplier specifies otherwise. Always check the certificate of analysis (CoA) for your specific batch. As with all research compounds, handling should follow institutional guidelines for research chemicals.

Sources

  1. Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1a, blinded, placebo-controlled, randomized, single- and multiple-ascending-dose study in healthy participants. — Diabetes, obesity & metabolism, 2023. PMID 37344954.
  2. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes. — The New England journal of medicine, 2025. PMID 40544435.
  3. Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1b, multicentre, blinded, placebo-controlled, randomized, multiple-ascending-dose study in people with type 2 diabetes. — Diabetes, obesity & metabolism, 2023. PMID 37264711.
  4. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. — The New England journal of medicine, 2025. PMID 40960239.
  5. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. — The New England journal of medicine, 2023. PMID 37351564.
  6. Emerging pharmacotherapies for obesity: A systematic review. — Pharmacological reviews, 2025. PMID 39952695.

Orforglipron FAQ

What is Orforglipron?
Orforglipron (LY3502970) is a small-molecule, non-peptide GLP-1 receptor agonist taken by mouth once daily. Unlike injectable GLP-1 drugs, it does not need to be injected. It is a research compound being studied for weight reduction in obesity and blood-sugar control in type 2 diabetes — it is not currently approved for medical use.[6][5]
How does Orforglipron work?
Orforglipron activates the GLP-1 receptor — the same target as injectable GLP-1 drugs like semaglutide. This signals the pancreas to release insulin, tells the brain to reduce appetite, and slows stomach emptying. Because it is a small synthetic molecule rather than a peptide, it survives digestion and can be swallowed. Its long half-life of roughly 25–68 hours supports once-daily dosing without food or water restrictions.[1]
What is Orforglipron used for in research?
Researchers are studying orforglipron primarily for two purposes: (1) reducing body weight in adults with obesity, where Phase 3 trials showed up to 11.2% average weight loss over 72 weeks,[4] and (2) lowering blood sugar (HbA1c) in adults with type 2 diabetes, where Phase 3 data showed average HbA1c reductions of roughly 1.2–1.5 percentage points over 40 weeks.[2]
How is Orforglipron dosed in research studies?
Doses in research have ranged from 0.3 mg (single-dose Phase 1 safety work) up to 45 mg per day (Phase 2 obesity trial). Phase 3 trials use once-daily oral doses of 3 mg, 6 mg, 12 mg, or 36 mg for 40–72 weeks depending on the condition being studied.[1][2][4] See the dosage chart on this page for the full breakdown.
How do you reconstitute Orforglipron?
Orforglipron does not require reconstitution. It is a small-molecule oral compound administered as a standard oral formulation in clinical research — no mixing, no syringes, no bacteriostatic water needed. This is one of its practical advantages over peptide-based GLP-1 compounds. For research use, follow your supplier's storage instructions and check the batch certificate of analysis.
Is Orforglipron safe based on current research?
In Phase 1–3 trials, the most common side effects were mild-to-moderate gastrointestinal effects (nausea, etc.), typically occurring during dose escalation — consistent with other GLP-1 receptor agonists.[4] No severe hypoglycemia was reported in the type 2 diabetes Phase 3 trial.[2] Treatment discontinuation due to adverse events ranged from roughly 5–10% across Phase 3 groups. This is a research compound; safety in broader populations has not been fully established.