FDA ApprovedFDA Approved

Orforglipron (Foundayo)

Oral GLP-1 Receptor Agonist | FDA-Approved for Weight Loss

Orforglipron (brand name Foundayo) is an FDA-approved oral, non-peptide GLP-1 receptor agonist and the first small-molecule GLP-1 approved for weight management. Approved April 2026 under the FDA's National Priority Voucher program, Foundayo can be taken once daily at any time without food or water restrictions. Clinical trials demonstrated up to 11.1% weight loss (24.9 lbs) at 72 weeks with the highest approved dose (17.2mg) and robust glycemic control (HbA1c reductions of 1.3-1.6%). Developed by Chugai Pharmaceutical and marketed by Eli Lilly. Available in 0.8mg, 2.5mg, 5.5mg, 9mg, 14.5mg, and 17.2mg tablets.

Daily dose

0.8-17.2mg daily

Frequency

Once daily

Cycle length

Long-term continuous therapy

Storage

Room temperature (15-30°C)

Key benefits

FDA-approved for weight loss (up to 11.1% at 72 weeks), robust diabetes control (HbA1c reduction 1.3-1.6%), once-daily oral tablet taken any time of day, no refrigeration or food/water restrictions, reduced cardiovascular risk markers, available as low as $25/month with insurance

How it works

Small-molecule GLP-1 receptor agonist with biased signaling - preferentially activates G protein/cAMP pathways (enhancing insulin secretion, suppressing glucagon, delaying gastric emptying, reducing appetite) while minimizing receptor desensitization. 79.1% oral bioavailability with 29-49 hour half-life supporting once-daily dosing.

Dosage protocols

Goal

Starting dose (first 30 days)

Dose

0.8mg daily · Once daily, any time

Route

Oral tablet

Goal

First titration (after 30 days)

Dose

2.5mg daily · Once daily, any time

Route

Oral tablet

Goal

Second titration (after 60 days)

Dose

5.5mg daily · Once daily, any time

Route

Oral tablet

Goal

Third titration (based on response)

Dose

9mg daily · Once daily, any time

Route

Oral tablet

Goal

Fourth titration (based on response)

Dose

14.5mg daily · Once daily, any time

Route

Oral tablet

Goal

Maximum approved dose

Dose

17.2mg daily · Once daily, any time

Route

Oral tablet

Research indications

weight Loss

Obesity Management Without Diabetes — FDA-approved based on ATTAIN-1 trial: 17.2mg dose achieved 11.1% weight loss (24.9 lbs) at 72 weeks in non-diabetic adults with obesity. 9mg achieved 8.3% (18.9 lbs), 5.5mg achieved 7.4% (17.2 lbs). First oral small-molecule GLP-1 approved for weight management.

Obesity Management With Type 2 Diabetes — ATTAIN-2 Phase 3 trial showed 9.6% weight loss (21.2 lbs) with 17.2mg in patients with both obesity and diabetes. 9mg achieved 7% (15.9 lbs), 5.5mg achieved 5.1% (11.7 lbs).

Cardiometabolic Risk Factor Improvement — Significant improvements in waist circumference, systolic blood pressure (8-12 mmHg reductions), triglycerides (-20-30%), and non-HDL cholesterol across Phase 3 trials. Comprehensive metabolic syndrome reversal.

Prediabetes Prevention — Among 1,127 ATTAIN-1 participants with prediabetes at baseline, up to 91% achieved near-normal blood sugar levels vs 42% with placebo, demonstrating diabetes prevention potential.

diabetes

Early Type 2 Diabetes Management — ACHIEVE-1 Phase 3 trial showed HbA1c reductions of 1.3-1.6% from 8.0% baseline over 40 weeks. 76.2% of patients achieved HbA1c <7%, 66.0% achieved ≤6.5%, positioning orforglipron as potential first-line oral therapy.

Insulin Resistance Improvement — Significant improvements in insulin sensitivity indices and fasting glucose reduction observed within 4 weeks of therapy initiation. Glucose-dependent mechanism prevents hypoglycemia risk in non-diabetic patients.

Beta Cell Function Preservation — GLP-1R agonism protects pancreatic beta cell function through multiple mechanisms including reduced glucotoxicity, enhanced glucose-responsive insulin secretion, and potential anti-apoptotic effects.

Long-term Glycemic Durability — Biased agonism profile favoring G protein over β-arrestin may reduce receptor desensitization, potentially improving sustained glycemic control compared to peptide GLP-1 agonists. Long-term studies ongoing.

cardiovascular

Cardiovascular Risk Marker Reduction — Significant improvements in blood pressure (systolic reductions 8-12 mmHg), triglycerides (-20-30%), HDL cholesterol increases, and reductions in small dense LDL particles observed across Phase 3 trials.

Obesity-Related Comorbidity Management — Being investigated for obstructive sleep apnea and hypertension in adults with obesity. GLP-1 class effects suggest potential benefits for cardiovascular event reduction, pending dedicated outcomes trials.

Metabolic Syndrome Reversal — Comprehensive improvements in all five metabolic syndrome criteria (waist circumference, blood pressure, triglycerides, HDL cholesterol, fasting glucose) demonstrated in clinical trials.

Administration

oral

Interactions

Avoid Combination

Semaglutide — Both are GLP-1 agonists - combining increases risk of severe hypoglycemia and excessive GI side effects including intractable nausea and vomiting

Avoid Combination

Tirzepatide — Dual GIP/GLP-1 agonist overlaps with GLP-1 mechanism - combination contraindicated due to additive hypoglycemic effects and severe GI toxicity

Avoid Combination

Liraglutide — Another GLP-1 agonist - concurrent use contraindicated due to overlapping mechanisms and compounded adverse effects

Monitor Combination

Insulin — Orforglipron enhances insulin sensitivity - may require significant insulin dose reduction to prevent hypoglycemia, requires close monitoring

Synergistic

Metformin — Complementary mechanisms for diabetes management - Phase 3 trials combining orforglipron with metformin showed enhanced efficacy without increased adverse events

Compatible

Dapagliflozin — SGLT-2 inhibitor with distinct mechanism - combination being evaluated in Phase 3 ACHIEVE-2 trial for potential additive metabolic benefits

Compatible

CJC-1295 — Growth hormone secretagogue may help preserve lean muscle mass during GLP-1-induced weight loss without interaction concerns

Compatible

Ipamorelin — May help maintain metabolic rate and muscle preservation during caloric restriction from orforglipron therapy

Compatible

BPC-157 — No known interactions - may theoretically support gut health and potentially mitigate GI side effects common with GLP-1 agonists

Compatible

5-Amino-1MQ — NNMT inhibition mechanism is distinct from GLP-1 pathway - may complement metabolic effects for enhanced optimization

Safety notes

BOXED WARNING: May cause thyroid C-cell tumors including medullary thyroid carcinoma (MTC). Contraindicated in patients with personal/family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)

Start at 0.8mg daily, titrate to 2.5mg after 30 days, then 5.5mg after 60 days - gradual titration minimizes GI side effects

Do not use with other GLP-1 receptor agonist medicines

Monitor for signs of acute pancreatitis (severe, persistent abdominal pain with or without nausea/vomiting) - stop taking Foundayo immediately if suspected

Common side effects: nausea, constipation, diarrhea, vomiting, indigestion, abdominal pain, headache, bloating, fatigue, belching, heartburn, gas, and hair loss

May cause dehydration leading to kidney problems - drink fluids to reduce risk, especially with nausea/vomiting/diarrhea

May affect oral contraceptive efficacy - use alternative birth control for 30 days after starting and after each dose increase

May require adjustment of insulin or sulfonylurea doses to prevent low blood sugar (hypoglycemia)

Not safe during pregnancy (may harm unborn baby) or breastfeeding - pregnancy exposure registry available at 1-800-LillyRx

Gallbladder problems reported - monitor for upper abdominal pain, fever, jaundice, or clay-colored stools

Tell healthcare providers you take Foundayo before any surgery or procedure using anesthesia (aspiration risk)

If doses missed for 7+ consecutive days, contact healthcare provider about how to restart treatment

Research studies

ATTAIN-1 Phase 3 Trial (Obesity) - 2025

3,127 adults with obesity without diabetes | 72-week study | FDA-approved doses: 5.5mg, 9mg, 17.2mg daily

Highest approved dose (17.2mg) achieved 11.1% weight loss (24.9 lbs) vs 2.1% placebo. 9mg achieved 8.3% (18.9 lbs), 5.5mg achieved 7.4% (17.2 lbs). First oral small-molecule GLP-1 to complete Phase 3. Significant improvements in waist circumference, blood pressure, triglycerides, and non-HDL cholesterol.

ATTAIN-2 Phase 3 Trial (Obesity + T2DM) - 2025

1,613 adults with obesity and type 2 diabetes | 72-week study | FDA-approved doses: 5.5mg, 9mg, 17.2mg daily

Highest approved dose (17.2mg) achieved 9.6% weight loss (21.2 lbs). 9mg achieved 7% (15.9 lbs), 5.5mg achieved 5.1% (11.7 lbs). Demonstrated efficacy extends to patients with comorbid diabetes and obesity.

ACHIEVE-1 Phase 3 Trial (Type 2 Diabetes) - 2025

559 adults with T2DM | 40-week study | 3mg, 12mg, 36mg daily doses

All doses significantly reduced HbA1c by 1.3-1.6% from 8.0% baseline vs 0.4% placebo. 76.2% achieved HbA1c <7%, 66.0% achieved ≤6.5%. 36mg dose produced 7.9% weight loss (16 lbs). First oral GLP-1 with no food/water restrictions to complete Phase 3.

Phase 2 Obesity Study - 2023

272 adults with obesity | 36-week study | Multiple dose escalations to 45mg

Achieved up to 14.7% mean weight reduction at 36 weeks with 45mg dose. Established dose-response relationship and optimal dosing ranges for Phase 3 development.

Phase 2 Type 2 Diabetes Study - 2023

Adult T2DM patients | 26-week study | Doses 3-45mg vs placebo and dulaglutide 1.5mg comparator

Demonstrated superior HbA1c reduction and body weight reduction compared to injectable dulaglutide across multiple dose levels, establishing proof-of-concept for oral efficacy matching injectables.

Phase 1 Safety and Pharmacokinetics Studies - 2023

92 healthy adults | Single and multiple ascending dose studies

Established 79.1% oral bioavailability, 29-49 hour half-life supporting once-daily dosing, and safety profile consistent with GLP-1 class. Confirmed no food effect on absorption, allowing unrestricted dosing.

Related compounds

Semaglutide Tirzepatide Retatrutide Mazdutide