Peptide Profile
Orforglipron
First oral non-peptide GLP-1 receptor agonist for diabetes and obesity
Dose Range
12 mg-36 mgmg
Frequency
Once daily
Route
oral
Cycle Length
Ongoing/indefinite
Onset
Moderate (1-2 weeks)
Evidence
Strong
Compound Profile
Scientific & Efficacy Data
C48H48F2N10O5
Molecular Formula
883.0 Da
Molecular Weight
25-68 hours (dose-dependent; enables once-daily oral dosing)
Half-Life
~79% oral bioavailability (food-independent)
Bioavailability
2212020-52-3
CAS #
137319706
PubChem ID ↗
Developed By · Phase 3 ongoing (2023-present); NDA submission expected 2026
Viking Therapeutics (formerly Aretes Pharmaceuticals)
Viking Therapeutics Inc.
Primary Benefits
12.4% weight loss at 36 mg in the ATTAIN-1 Phase 3 trial, with 65% of patients achieving greater than 10% weight loss — delivered via convenient oral dosing
HbA1c reduction of 2.2% in ACHIEVE-3 trial, demonstrating superiority over oral semaglutide (1.4%) with nearly 3x more patients reaching target HbA1c <7%
50.6% reduction in hsCRP inflammatory marker at 36 mg dose, along with improvements in non-HDL cholesterol, triglycerides, and systolic blood pressure
Amino Acid Sequence
KGDG-KGDG-DLKDGADosing
How much
do I take?
Timing
Best time to take
Take Orforglipron at the same time each day for consistent blood levels. Morning dosing with breakfast is often preferred, but follow your healthcare provider's specific instructions.
With food?
Orforglipron can typically be taken with or without food. Taking it with a light meal may help reduce any GI discomfort. Avoid taking with grapefruit juice or high-fat meals unless specifically directed.
If stacking
Orforglipron should be used as directed by your healthcare provider. If combining with other medications or supplements, discuss potential interactions with your provider. Avoid combining with compounds that have overlapping mechanisms unless specifically guided by a medical professional.
Adjusting Your Dose
Increase if
- +You've tolerated the current dose for the recommended period without significant side effects
- +Therapeutic goals haven't been met at the current dose level
- +Your healthcare provider recommends dose escalation based on your response
- +Lab work or clinical assessments support a higher dose
Decrease if
- -Side effects are bothersome or impacting daily life despite management strategies
- -You experience any signs of an adverse reaction
- -Lab results indicate the need for dose reduction
- -Your healthcare provider recommends a lower dose based on your response
Signs of right dose
- ✓Therapeutic goals being met with minimal side effects
- ✓Stable and consistent response to treatment
- ✓Lab values or clinical markers trending in the right direction
- ✓Good tolerance with manageable or absent side effects
Dosing Calculator
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Suitability
Is this
right for me?
Best For
Oral GLP-1 receptor agonism without injection burden
Orforglipron is particularly well-suited for individuals focused on oral glp-1 receptor agonism without injection burden. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Weight management in obesity with or without type 2 diabetes
Orforglipron is particularly well-suited for individuals focused on weight management in obesity with or without type 2 diabetes. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Glycemic control in type 2 diabetes as add-on to metformin
Orforglipron is particularly well-suited for individuals focused on glycemic control in type 2 diabetes as add-on to metformin. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Cardiovascular risk reduction through weight loss and metabolic improvements
Orforglipron is particularly well-suited for individuals focused on cardiovascular risk reduction through weight loss and metabolic improvements. Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Consider Alternatives If
Who Should Avoid
Do not use if
- ×Personal or family history of medullary thyroid carcinoma (GLP-1 class precaution)
- ×Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- ×Known hypersensitivity to orforglipron or excipients
- ×History of pancreatitis (use with caution)
Use with caution if
- !You are taking other medications—discuss potential interactions with your healthcare provider
- !You have a history of liver or kidney disease
- !You are elderly or have multiple medical conditions
- !You are planning surgery in the near future—inform your surgeon about Orforglipron use
- !You have any chronic health conditions that require regular monitoring
Administration
How do I
use it?
Reconstitution
What you need
- •Orforglipron in its prescribed form
- •Clean, dry storage container
- •Measuring device if applicable (oral syringe, measuring cup)
- •Calendar or reminder app for dosing schedule
Injection
Route
Orforglipron is administered oral—no injection required
Best sites
- •Not applicable—this is not an injectable formulation
Technique
- 1.Follow the specific administration instructions for your Orforglipron formulation
- 2.Take or apply as directed by your healthcare provider
- 3.Store properly between uses according to package instructions
Storage
Signs of degradation
Sample Daily Schedule
Safety
Is it
safe?
Safety Profile
Orforglipron (MK-0731) completed Phase II trials for type 2 diabetes with favorable safety profile at oral doses of 10-40 mg daily. Gastrointestinal side effects (nausea, vomiting) occurred in 20-30% of subjects but were dose-dependent and generally mild. As a GLP-1 receptor agonist, risks include potential medullary thyroid carcinoma (black box warning category) and acute pancreatitis, requiring thyroid screening before treatment initiation and patient education on symptoms.
Eli Lilly Phase II RCTs (n=400+) demonstrated orforglipron mechanism through GLP-1R binding (Ki 0.04 nM) with HbA1c reductions of 0.8-1.2% over 12 weeks versus placebo. Oral bioavailability improved versus earlier GLP-1 analogs through enhanced pepsin resistance and intestinal absorption. Long-term safety monitoring showed weight loss of 2-4 kg with glucose-dependent hypoglycemia risk only in combination with sulfonylureas.
Common Side Effects
Experienced by some users
Nausea
The most commonly reported adverse event, consistent with the GLP-1 receptor agonist class. Dose-dependent and most frequent during dose escalation. Generally mild to moderate.
Management: Gradual dose escalation minimizes incidence. Symptoms typically improve with continued treatment. Smaller, more frequent meals may help. If severe, pause escalation at current dose level.
Constipation
Common gastrointestinal effect related to GLP-1R-mediated slowing of gut motility. Reported across dose levels in Phase 3 trials.
Management: Increase dietary fiber and fluid intake. Mild laxatives if needed. Usually manageable and does not require dose adjustment.
Diarrhea
GI disturbance from GLP-1 receptor activation affecting intestinal motility and secretion. Generally transient and self-limiting.
Management: Maintain hydration. Usually resolves without intervention. Contact prescriber if persistent or severe.
Vomiting
Occurs alongside nausea, particularly during dose titration. Related to central and peripheral GLP-1R activation.
Management: Slow dose escalation. Ensure adequate hydration. Anti-emetics if needed. Temporarily hold dose increase if recurrent.
Less Common
- •Heart Rate Increase
These typically resolve with continued use or dose adjustment.
Stop and Seek Help If
- ×Severe or worsening side effects that don't improve with dose adjustment or supportive care
- ×Signs of an allergic reaction—rash, hives, swelling, or difficulty breathing
- ×Your healthcare provider recommends discontinuation based on your clinical response
- ×Development of any new medical condition that may be contraindicated with Orforglipron
- ×Pregnancy or planning to become pregnant (unless specifically approved for use during pregnancy)
- ×Abnormal lab results or clinical markers that suggest adverse effects
Orforglipron should only be started, adjusted, or discontinued under medical supervision. This information is for educational purposes only and does not replace professional medical advice. Never stop a prescribed treatment without consulting your healthcare provider first, as abrupt discontinuation may have consequences.
Interactions
With other peptides
- ✓Complementary mechanisms — metformin provides insulin sensitization while orforglipron offers GLP-1R-mediated glucose-dependent insulin secretion and appetite suppression
- ✓Independent glucose-lowering via renal glucose excretion with demonstrated cardiorenal benefits complements oral GLP-1 agonism
- ✓Caloric restriction synergizes with orforglipron's appetite suppression for enhanced weight loss outcomes
With medications
- !Injectable GLP-1 Receptor Agonists - Redundant GLP-1R activation with no additional benefit and increased gastrointestinal adverse events
- !DPP-4 Inhibitors - Overlapping incretin pathway stimulation provides minimal additional efficacy when combined with a direct GLP-1R agonist
- !Sulfonylureas - Increased hypoglycemia risk from non-glucose-dependent insulin secretion combined with GLP-1R-mediated insulin release
With supplements
- ✓Multivitamins - Generally safe to take alongside Orforglipron. Space doses apart if taking oral formulations to ensure optimal absorption.
- ✓Electrolyte supplements - Helpful if experiencing any GI side effects that could lead to dehydration. Safe to combine.
Effectiveness
Does it
work?
Evidence Level
Strong human trials
What to Expect
Weeks 1-8
What you might notice
- •Dose escalation period from 3 mg to target maintenance
- •GI side effects (nausea, constipation) peak during this phase
- •Early appetite reduction and initial weight loss
What's normal
- •Nausea is common and expected during dose titration
- •Appetite naturally decreases as GLP-1R activation increases
- •Early weight loss of 2-4% may occur
- •GI symptoms gradually improve as the body adjusts
What's next
- →Reach target maintenance dose (12 or 36 mg)
- →GI tolerability typically improves significantly after dose stabilization
Weeks 8-24
What you might notice
- •Steady weight loss acceleration at maintenance dose
- •HbA1c improvements becoming measurable
- •GI side effects largely resolved
- •Reduced appetite stabilizes
What's normal
- •Weight loss of 5-8% at this timepoint
- •HbA1c dropping significantly in T2DM patients
- •Blood pressure and lipid improvements beginning
- •Most patients tolerate medication well
What's next
- →Continue maintenance dose
- →HbA1c assessment at 12-16 weeks reflects cumulative glycemic benefit
Weeks 24-72
What you might notice
- •Continued weight loss approaching 10-12% at 36 mg
- •Sustained metabolic improvements
- •Cardiovascular risk markers (hsCRP, lipids, BP) showing significant improvement
What's normal
- •In ATTAIN-1 trial, 12
- •4% weight loss at 36 mg over 72 weeks
- •65% of patients achieved >10% weight loss
- •6% reduction in hsCRP
- •HbA1c reductions sustained
What's next
- →Long-term maintenance
- →Phase 3 cardiovascular outcomes trial (ATTAIN-Outcomes) will define long-term cardiovascular benefit
Signs It's Working
Treatment Response
- ✓Improvement in the primary symptoms or condition being treated
- ✓Positive changes in relevant lab values or clinical markers
- ✓Consistent, stable response to Orforglipron over time
- ✓Reduction in symptom frequency or severity
General Well-being
- ✓Improved energy levels and daily functioning
- ✓Better quality of life related to the treated condition
- ✓Manageable or absent side effects indicating good tolerance
- ✓Positive feedback from healthcare provider during check-ups
Not Seeing Results?
Common reasons
- •Not at therapeutic dose yet—initial doses are for building tolerance, not maximum effect
- •Insufficient time at target dose—most compounds need several weeks to show full benefits
- •Inconsistent dosing schedule—regular, consistent use is crucial for optimal results
- •Individual variation in response—genetics, metabolism, and other factors affect outcomes
- •Underlying conditions or medications interfering with absorption or effectiveness
- •Improper storage leading to degraded product—always verify proper storage conditions
Key Research
"Orforglipron (LY3502970): A Phase 1a study in healthy participants"
Knop FK, Benson CT, Skarsgard JK, et al., 2023
Finding: Orforglipron represents a novel therapeutic approach for metabolic disease.
View Study"Orforglipron (LY3502970): A Phase 1b study in people with type 2 diabetes"
Pratt E, Ma X, Liu R, et al., 2023
Finding: Research (2023) on orforglipron contributes important scientific knowledge about its biological and pharmacological properties.
View Study"Orforglipron: A Novel Oral GLP-1 Agonist for Obesity and Diabetes"
Pillai AA, Sharma AM, Krayem H, et al., 2025
Finding: Research (2025) on orforglipron contributes important scientific knowledge about its biological and pharmacological properties.
View Study"Efficacy and Safety of Oral GLP-1 RA Orforglipron: A Systematic Review and Meta-Analysis"
Hammad N, Ramadan AM, Nazmy A, et al., 2026
Finding: Research (2026) demonstrates orforglipron's efficacy in clinical treatment and therapeutic applications.
View Study"Efficacy and safety of danuglipron and orforglipron: a systematic review and meta-analysis"
Zhou J, Wang F, Li S, et al., 2025
Finding: Research (2025) demonstrates orforglipron's efficacy in clinical treatment and therapeutic applications.
View StudyFrequently Asked Questions