Orforglipron (LY-3502970) is an oral, non-peptide,

small-molecule In molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs are small molecules; t ...

GLP-1 receptor agonist Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, GLP-1RAs, or incretin mimetics, are a class of anorectic drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of ...

developed as a

weight loss drug Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control excess body fat. These medications alter one of the fundamental processes of the human body, weight regulation, by: reducing appetite and con ...

Eli Lilly and Company Eli Lilly and Company, Trade name, doing business as Lilly, is an American multinational Medication, pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 count ...

. It was discovered by Chugai Pharmaceutical Co., then was

licensed A license (American English) or licence (Commonwealth English) is an official permission or permit to do, use, or own something (as well as the document of that permission or permit). A license is granted by a party (licensor) to another part ...

to Lilly in 2018. Orforglipron is easier to produce than existing peptide GLP-1 agonists and is expected to be cheaper.

Mechanism

Orforglipron is a

, partial GLP-1 receptor agonist affecting the activity of

cyclic adenosine monophosphate Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine tri ...

(cAMP); its effects are similar to the actions of

glucagon-like peptide-1 Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and cer ...

(GLP-1) for reducing food intake and lowering

blood glucose The blood sugar level, blood sugar concentration, blood glucose level, or glycemia is the measure of glucose concentrated in the blood. The body tightly blood sugar regulation, regulates blood glucose levels as a part of metabolic homeostasis ...

levels.

Clinical trials

The results of Phase I safety and Phase II ascending-dose

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s enrolling people with

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

type 2 diabetes Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...

were published in 2023. Orforglipron has a

half-life Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''Half Life: ...

of 29 to 49 hours across the doses tested and is taken once per day by mouth without food or water restrictions. Safety and dosing trials showed that the incidence of

adverse event In pharmaceuticals, an adverse event (AE) is any unexpected or harmful medical occurrence that happens to a patient during medical treatment or a clinical trial. Unlike direct side effects, an adverse event does not necessarily mean the medicati ...

s in orforglipron-treated participants was 62–89%, mostly from

gastrointestinal discomfort Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the Human gastrointestinal tract, gastrointestinal tract, namely the esophagus, stomach, small intestine, large intestine and rectum; and the accessory or ...

(44–70% with orforglipron, 18% with placebo) having mild to moderate severity. The most common side effects of orforglipon are

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

, upset stomach, and

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...

. The ability of orforglipron to reduce blood sugar levels and body weight was judged favorable compared to

dulaglutide Dulaglutide, sold under the brand name Trulicity among others, is a medication used for the treatment of type 2 diabetes in combination with diet and exercise. It is also approved in the United States for the reduction of major adverse cardio ...

Phase III ACHIEVE-1 trial

In April 2025, results from a

Phase III clinical trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phase ...

involving 559 people with type 2 diabetes who took an oral orforglipron pill,

injectable An injection (often and usually referred to as a "shot" in US English, a "jab" in UK English, or a "jag" in Scottish English and Scots) is the act of administering a liquid, especially a drug, into a person's body using a needle (usually a hyp ...

or a

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

daily for 40 weeks showed that orforglipron produced a reduction in blood glucose levels by 1.3 to 1.6 percentage points from a starting level of 8%. More than 65% of participants taking the highest dose of orforglipron achieved a reduction of

hemoglobin A1C Glycated hemoglobin, also called glycohemoglobin, is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose, and fructose, spontaneously (that is, enzyme, non-enzymatically) bond with h ...

level by more than or equal to 1.5 percentage points, bringing them into the non-diabetic range as defined by the

American Diabetes Association The American Diabetes Association (ADA) is a United States-based nonprofit that seeks to educate the public about diabetes and to help those affected by it through funding research to manage, cure and prevent diabetes, including type 1 diabetes ...

. People taking the highest dose of the pill lost 8% of their weight, or around , on average after 40 weeks. Side effects were similar to those seen with other GLP-1 agonists, and no significant liver problems were observed.

References

External links

What to Know About Eli Lilly’s Daily Pill for Weight Loss
The New York Times, April 17, 2025 {{Oral hypoglycemics and insulin analogs Experimental anti-obesity drugs GLP-1 receptor agonists Fluoroarenes Indazoles Imidazoles Pyrazolopyridines Oxadiazoles Cyclopropanes

Mechanism

Clinical trials

Phase III ACHIEVE-1 trial

See also

References

External links