Metabolic & Fat Loss FDA Phase 3

Orforglipron

Also known as: LY3502970, OWL833

Molecular Identifiers

Molecular Formula

C48H48F2N10O5

CAS Number

2212020-52-3

PubChem CID

137319706

Molecular Weight

882.97 Da

Overview

Non-peptide oral GLP-1 receptor agonist, with a molecular weight of approximately 883 Da. Represents a new class of small molecule GLP-1 agonists administered orally, overcoming the bioavailability limitations of peptide analogs. In advanced clinical development for type 2 diabetes and obesity.

In phase 3 clinical trials for type 2 diabetes and obesity, developed by Eli Lilly. First non-peptide oral GLP-1 agonist with promising results of up to 14.7% weight loss in phase 2.

The main clinical interest in orforglipron is GLP-1 receptor agonism in a small-molecule format administered orally, eliminating the need for weekly injections. Sought effects include weight loss, glycemic control in type 2 diabetes, appetite reduction, and delayed gastric emptying. Phase 2 studies reported up to 14.7% weight loss at 36 weeks, with gastrointestinal adverse effects similar to those of injectable GLP-1 agonists.

It is in phase 3 clinical trials, developed by Eli Lilly, and is not yet approved by the FDA, EMA, or ANVISA. Current availability is restricted to research settings. Administration is oral, once daily, with gradual dose escalation (12-36 mg) to mitigate nausea, vomiting, and diarrhea.

It represents the first generation of oral non-peptide GLP-1 agonists to reach phase 3 — a milestone that could redefine the treatment logistics of obesity and diabetes, currently dominated by injectable peptide analogs such as semaglutide and tirzepatide.

Within the subset of oral GLP-1 agonists, its core difference compared with oral semaglutide (Rybelsus) is structural: while Rybelsus is the same peptide as Ozempic formulated with an absorption enhancer (SNAC) and requires strict fasted administration, orforglipron is a non-peptide small molecule with more predictable oral bioavailability independent of fasting, at least in the published phase 2 protocols.

Small molecule — non-peptide oral GLP-1 receptor agonist

Half-life

~29-49 hours

Administration Route

Oral

Mechanism of Action

GLP-1 receptor agonism as a non-peptide oral small molecule
Stimulation of glucose-dependent insulin secretion
Suppression of postprandial glucagon secretion
Reduction of appetite and caloric intake via central signaling
Delayed gastric emptying
Improved insulin sensitivity in peripheral tissues

Dosage Protocol

Data compiled from the literature. This does not constitute medical advice.

Parameter	Value
Dose	12-36 mg per day (oral)
Frequency	Once daily
Timing	Morning, with or without food
Duration	Continuous use (with gradual dose escalation)

Reported Side Effects

Adverse effects described in the literature. Severity and frequency vary between individuals.

Nausea
Vomiting
Diarrhea
Decreased appetite
Constipation

Product Properties

Purity	>99%
Appearance	White to off-white powder or oral tablet/capsule
Solubility	Not applicable — oral solid dosage form
Source	Chemical synthesis
Storage	Room temperature (15-25°C) in a dry place for up to 2 years. Protect from moisture. Keep in original packaging.