What side effects are associated with this type of intervention?

GLP-1 receptor agonists, such as liraglutide and exenatide, are commonly used for obesity treatment. Known side effects include gastrointestinal symptoms like nausea, vomiting, and diarrhea. There is also a potential risk for benign and malignant thyroid C cell tumors, as observed in rodent studies, though this risk in humans remains unclear. Additionally, these medications have been associated with an increased risk of acute pancreatitis. Patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia are advised against using these treatments.

What prior FDA approvals exist?

Several GLP-1 receptor agonists have been approved by the FDA for the treatment of obesity. Liraglutide (brand name Saxenda) was approved for chronic weight management in adults with a BMI of 30 kg/m2 or greater, or 27 kg/m2 or greater with at least one weight-related condition. Clinical trials demonstrated significant weight loss and improvements in cardiometabolic risk factors. Another GLP-1 receptor agonist, semaglutide (brand name Wegovy), was also approved for weight management in similar patient populations, showing even greater efficacy in weight reduction. Both drugs have been shown to improve glycemic control and reduce the risk of developing type 2 diabetes in patients with prediabetes. Safety profiles include common side effects such as gastrointestinal symptoms, and they are not recommended for individuals with a history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.

What other types of research exist?

Promising alternatives to Orforglipron for obesity treatment include Liraglutide (3.0 mg daily), Semaglutide (once weekly), and Tirzepatide. These GLP-1 receptor agonists have demonstrated significant weight loss in clinical trials and are approved for weight management. Additionally, new medications like Setmelanotide, targeting different pathways, are emerging as potential treatments.

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Orforglipron for Obesity

Phase 1

Waitlist Available

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have an estimated glomerular filtration rate equal to or greater than 60 milliliters per square meter (mL/m2).

Be older than 18 years old

Must not have

Have any type of diabetes with hemoglobin A1c (HbA1c) level of 6.5% or greater.

Have significant history of or currently have Major Depressive Disorder or psychiatric disorder within the last 2 years.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up predose up to 24 hours postdose

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new pill called orforglipron in healthy overweight and obese people. Researchers want to see how orforglipron affects the levels of other drugs in the blood and how quickly these drugs are removed from the body. They are also studying how sodium bicarbonate affects one of these drugs, simvastatin, when taken together. The study will also check for any side effects.

Who is the study for?

This trial is for healthy overweight and obese individuals. Participants should not have any other significant health issues that could interfere with the study.

What is being tested?

The study is testing how orforglipron affects the absorption and elimination of several drugs (digoxin, rosuvastatin, acetaminophen, midazolam, simvastatin) in overweight/obese people. It also examines the impact of sodium bicarbonate on drug levels when taken with orforglipron.

What are the potential side effects?

Possible side effects include reactions to orforglipron or other studied drugs such as digestive discomfort, headaches, dizziness, potential liver enzyme changes, and allergic responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function is normal or only mildly reduced.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My diabetes is confirmed with an HbA1c level of 6.5% or higher.

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I have had major depression or a psychiatric disorder in the last 2 years.

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My obesity is caused by an endocrine disorder like Cushing's or Prader-Willi syndrome.

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I have had weight loss surgery.

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I or my close family have a history of specific thyroid or endocrine conditions.

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I am allergic to midazolam, simvastatin, rosuvastatin, or digoxin.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ predose up to 24 hours postdose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~predose up to 24 hours postdose

This trial's timeline: 3 weeks for screening, Varies for treatment, and predose up to 24 hours postdose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

PK: Maximum Observed Concentration (Cmax) of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC [0-∞]) of Simvastatin and simvastatin acid following simultaneous administration of Orforglipron capsule formulation

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Orforglipron (Part 2)Experimental Treatment4 Interventions

Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin and Sodium Bicarbonate administered orally.

Group II: Orforglipron (Part 1)Experimental Treatment7 Interventions

Participants will receive Orforglipron capsule and tablet formulation with Simvastatin, Digoxin, Rosuvastatin, Acetaminophen, Midazolam and Sodium Bicarbonate administered orally.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Digoxin

2017

Completed Phase 4

~670

Sodium Bicarbonate

2015

Completed Phase 4

~2060

Rosuvastatin

2019

Completed Phase 4

~3150

Midazolam

2018

Completed Phase 4

~1910

Acetaminophen

2017

Completed Phase 4

~2030

Orforglipron

2024

Completed Phase 1

~80

Simvastatin

2012

Completed Phase 4

~1270

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for obesity, particularly GLP-1 receptor agonists like liraglutide and semaglutide, work by mimicking the incretin hormone GLP-1. These drugs enhance glucose-dependent insulin release, slow gastric emptying, and reduce appetite by acting on the brain's satiety centers. This results in reduced food intake and improved glycemic control, which are crucial for weight loss and the management of obesity-related comorbidities. For obesity patients, these mechanisms are significant as they not only aid in weight reduction but also improve overall metabolic health, reducing the risk of developing type 2 diabetes and cardiovascular diseases.