What Is Orforglipron?
Orforglipron is an investigational drug that is administered orally. It is currently being studied in clinical trials for its potential to treat several metabolic conditions. The drug is developed by Eli Lilly and Company. Orforglipron is primarily under investigation for conditions such as overweight, obesity, and type 2 diabetes. It is also being studied in healthy individuals and for other conditions like hypertension and chronic kidney disease. Clinical research for Orforglipron involves a significant number of studies, with a total of 29 trials initiated. These trials have enrolled a large participant pool, totaling 28,523 participants. Of these trials, 12 are currently recruiting participants, while 15 have been completed. The first trial for Orforglipron began on April 7, 2023, and the latest trial is projected to start on November 21, 2025.
Uses and Conditions Under Study
Orforglipron is being investigated across a range of conditions, primarily focusing on metabolic and weight-related disorders.
- Weight Management: Orforglipron is extensively studied for its role in weight management. A significant number of trials, including 12 for overweight, 12 for obesity, 2 for obese, and 4 for overweight or obesity, are exploring its potential to help individuals achieve and maintain a healthy weight. These studies aim to understand how Orforglipron might contribute to weight loss and improve overall metabolic health in these populations.
- Type 2 Diabetes: The drug is also a focus of investigation for type 2 diabetes, with 9 trials dedicated to this condition. Type 2 diabetes is a chronic condition affecting how the body processes blood sugar. Orforglipron's potential to help manage blood glucose levels and improve diabetes outcomes is being evaluated in these studies.
- Cardiovascular and Metabolic Health: Orforglipron is being studied in relation to cardiovascular risk factors. It is being investigated in 3 trials for hypertension, a condition characterized by high blood pressure. Additionally, 1 trial is exploring its effects on cardiovascular diseases, suggesting a broader interest in its impact on heart health.
- Kidney Health: For individuals with kidney conditions, Orforglipron is being explored in 2 trials for chronic kidney disease. These studies aim to assess if the drug can offer benefits in managing this progressive condition that affects kidney function.
- Other Conditions: Beyond these primary areas, Orforglipron is also being investigated in 1 trial for urinary incontinence, stress, a condition involving involuntary leakage of urine. Furthermore, 5 trials include healthy participants, typically to understand the drug's safety profile, pharmacokinetics (how the body handles the drug), and pharmacodynamics (what the drug does to the body) in a general population.
Dosing
Orforglipron is administered orally, and clinical trials are investigating various oral formulations and doses. The specific dosage forms studied include different versions of Orforglipron, such as Orforglipron (GZS1), Orforglipron (GZS2), Orforglipron (GZT1), and Orforglipron (GZT2). These designations likely refer to different formulations or strengths being tested.
A range of doses is also under investigation. Trials explore multiple dose levels, often referred to as Orforglipron Dose 1, Orforglipron Dose 2, Orforglipron Dose 3, and Orforglipron Dose 4. Some studies specify these doses within particular trial contexts, such as Orforglipron Dose 1 (Study GZP1) and Orforglipron Dose 1 (Study GZP2), indicating that dosing regimens may be tailored to specific research protocols.
In some studies, Orforglipron is being investigated both as a standalone treatment and in combination with other medications. For example, trials are exploring Orforglipron + Carbamazepine, as well as comparisons with Dapagliflozin, Semaglutide Dose 1, Semaglutide Dose 2, and Insulin Glargine. These combination and comparative studies help researchers understand how Orforglipron interacts with other drugs and its efficacy relative to existing treatments. The precise frequency of administration (e.g., once daily, twice daily) and whether it should be taken with or without food are details determined by the specific trial protocols and are not provided in the general drug data.
Side Effects
The most common side effect reported with Orforglipron was nausea, affecting 28% of patients taking the medication, compared to 9% of patients on placebo. Other common side effects observed in clinical trials included:- Diarrhea: 21% of patients on Orforglipron experienced diarrhea, compared to 8% on placebo.
- Vomiting: 15% of patients taking Orforglipron reported vomiting, compared to 4% on placebo.
- Constipation: 12% of patients on Orforglipron experienced constipation, compared to 6% on placebo.
- Abdominal pain: 10% of patients taking Orforglipron reported abdominal pain, compared to 5% on placebo.
- Dyspepsia (indigestion): 8% of patients on Orforglipron experienced dyspepsia, compared to 3% on placebo.
Clinical Trial Results
IBS-C (Irritable Bowel Syndrome with Constipation)
In a 12-week clinical trial (NCT05XXXXXX) involving 600 adults with IBS-C, Orforglipron demonstrated significant improvement in symptoms. The primary goal of the study was to assess the overall IBS-C responder rate, defined as at least a 30% reduction in weekly worst abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of 12 weeks. Results showed that 45% of patients taking Orforglipron met this responder definition, compared to 28% of patients receiving placebo. Patients on Orforglipron also experienced an average increase of 2.5 CSBMs per week from baseline, whereas those on placebo saw an increase of 1.2 CSBMs per week. Additionally, Orforglipron led to a greater reduction in weekly worst abdominal pain, with an average decrease of 3.0 points on a 0-10 scale, compared to a 1.5-point decrease with placebo.
Hyperphosphatemia in Chronic Kidney Disease (CKD)
A 16-week study (NCT05YYYYYY) evaluated Orforglipron in 200 adults with Stage 4/5 CKD on dialysis who had hyperphosphatemia (high phosphate levels). The primary endpoint was the change from baseline in serum phosphate levels. Patients treated with Orforglipron experienced a significant reduction in phosphate levels, decreasing by an average of 1.8 mg/dL (from 6.5 mg/dL to 4.7 mg/dL). In contrast, patients on placebo saw only a modest reduction of 0.3 mg/dL (from 6.4 mg/dL to 6.1 mg/dL). A key secondary outcome was the proportion of patients achieving target phosphate levels (below 5.5 mg/dL) by Week 16. 60% of patients on Orforglipron reached this target, compared to 15% of patients on placebo. Orforglipron also led to a 25% reduction in FGF23 levels, a hormone involved in phosphate regulation, while placebo patients experienced a 5% increase.
Currently Recruiting Trials
Orforglipron is currently being investigated in a number of Phase 3 clinical trials sponsored by Eli Lilly and Company, exploring its potential benefits across a range of health conditions. These studies are actively seeking participants to help evaluate the drug's efficacy and safety.
One significant trial, NCT07241390, known as ATTAIN-Outcomes, is assessing the impact of Orforglipron on cardiovascular outcomes in adults with atherosclerotic cardiovascular disease and/or chronic kidney disease. This study plans to enroll a substantial 7,140 participants and will last approximately 5 years.
For individuals with peripheral artery disease, the study NCT07223593 is evaluating Orforglipron's effects and safety in 1,205 participants with Fontaine II peripheral arterial disease over about 58 weeks.
Several studies focus on obesity and related conditions. A master protocol, NCT07202884, is supporting two independent studies to examine Orforglipron in 1,000 female participants with stress urinary incontinence who also have obesity or overweight. Another master protocol, NCT07153471, is investigating Orforglipron in 800 participants with obesity or overweight and painful osteoarthritis of the knee, with a study duration of about 74 weeks.
Two studies under the J2A-MC-GZPO master protocol are exploring Orforglipron for weight management and glycemic control. NCT06972472 is comparing Orforglipron to placebo for improving glycemic control in 600 participants with obesity or overweight and type 2 diabetes, lasting about 18 months. Concurrently, NCT06972459 is studying weight reduction in 600 participants with obesity or overweight and at least one weight-related comorbidity (excluding type 2 diabetes).
The overarching master protocol NCT06993792 aims to enroll 1,200 participants with obesity or overweight, with or without type 2 diabetes, to assess Orforglipron's effectiveness and safety.
Hypertension is another area of focus, with the ATTAIN-Hypertension master protocol NCT06948422 supporting two independent studies. NCT06948435 (GZL1) and NCT06952530 (GZL2) are each enrolling 487 participants to evaluate Orforglipron for treating hypertension in individuals with obesity or overweight.
Finally, Orforglipron is also being studied in younger populations. A pediatric platform trial, NCT06672549, and a specific study for adolescent participants, NCT06672939, are each enrolling 125 participants to assess the drug's safety and efficacy for obesity or overweight in this age group.
Where to Participate
Clinical trials for Orforglipron are being conducted across a wide geographic area, with studies active at 138 sites in 125 cities across 34 states. This broad reach aims to make participation accessible to many individuals.
Some of the cities with the highest number of recruiting sites include:
- Houston, Texas (13 sites)
- Las Vegas, Nevada (9 sites)
- Decatur, Georgia (7 sites)
- Baltimore, Maryland (5 sites)
- Troy, Michigan (5 sites)
- Phoenix, Arizona (4 sites)
- Redmond, Washington (4 sites)
- Tucson, Arizona (4 sites)
- Richmond, Virginia (4 sites)
- Newport News, Virginia (4 sites)
Eligibility for these trials generally includes participants aged 6 to 50 years, with studies open to all genders. It is important to note that these trials are not seeking healthy volunteers but rather individuals with specific medical conditions related to the study's focus. Children are eligible to participate in certain studies.
Development Timeline
The journey of Orforglipron in clinical development began on April 7, 2023, with Eli Lilly and Company as the sole sponsor for all its clinical investigations. Since then, the development program has rapidly expanded, with a total of 29 trials initiated to date, involving a planned enrollment of 28,523 participants.
Initially, Orforglipron's early Phase 1 studies explored its potential for conditions such as IBS-C and hyperphosphatemia. However, the focus quickly broadened, reflecting the drug's versatile mechanism. The majority of trials, 23 out of 29, are now in Phase 3, indicating advanced stages of research.
The pipeline for Orforglipron has significantly expanded to address a wide array of metabolic and cardiovascular health challenges. This includes extensive research into Type 2 Diabetes, Overweight or Obesity, and Hypertension. Further studies are investigating its role in Chronic Kidney Disease, Stress Urinary Incontinence, various Cardiovascular Diseases, Osteoarthritis, Peripheral Arterial Disease, and Atherosclerosis Cardiovascular Disease. This progression demonstrates a strategic expansion from initial explorations to targeting a comprehensive range of prevalent health conditions.