What side effects are associated with this type of intervention?

Common treatments for obesity, particularly GLP-1 receptor agonists like liraglutide and semaglutide, are associated with several side effects. These include gastrointestinal issues such as nausea, vomiting, and diarrhea. There is also a potential risk for pancreatitis and, in rodent studies, an association with thyroid C cell tumors, although this risk is not well established in humans. Other side effects can include injection site reactions and, less commonly, gallbladder-related issues like cholelithiasis. It is important for patients to discuss these potential risks with their healthcare provider to determine the most appropriate treatment plan.

What prior FDA approvals exist?

The FDA has approved several GLP-1 receptor agonists for the treatment of obesity. Liraglutide (brand name Saxenda) was approved based on trials showing significant weight loss compared to placebo. In a 56-week trial, patients treated with liraglutide experienced a mean weight loss of 8.0 kg compared to 2.6 kg with placebo. Another GLP-1 receptor agonist, semaglutide, has also shown efficacy in weight management. These drugs work by mimicking the incretin hormone GLP-1, which increases insulin secretion, decreases glucagon secretion, and slows gastric emptying, leading to reduced appetite and caloric intake.

What other types of research exist?

Promising alternatives to Orforglipron for obesity treatment include: 1) Liraglutide (GLP-1 receptor agonist) which has shown significant weight loss and cardiovascular benefits. 2) Semaglutide (GLP-1 receptor agonist) which has demonstrated superior efficacy in weight reduction. 3) Tirzepatide, a dual GIP and GLP-1 receptor agonist, which has shown promising results in weight loss and glycemic control. 4) Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, which are associated with moderate weight loss and cardiovascular benefits.

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Hormone Therapy

Orforglipron for Type 2 Diabetes and Obesity (ACHIEVE-4 Trial)

Verified Trial

Phase 3

Recruiting

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 been diagnosed with type 2 diabetes mellitus (T2DM)

Are at least 18 years of age or legal age of consent in the jurisdiction in which the study is taking place, whichever is older.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to end of the study (approximately 104 weeks)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new diabetes medication called orforglipron to see if it is safer and more effective than insulin in people with type 2 diabetes who are overweight or obese and at higher risk for heart problems. The study will last several years and involve multiple visits.

Who is the study for?

This trial is for adults with type 2 diabetes and obesity or overweight, who also have a higher risk of heart disease. Participants should not be on insulin therapy but may be taking other diabetes medications.

What is being tested?

The study tests the safety and effectiveness of a daily oral medication called Orforglipron compared to Insulin Glargine, an injectable insulin, over about two years with up to 27 visits.

What are the potential side effects?

Possible side effects from Orforglipron could include digestive issues, changes in blood sugar levels, fatigue, and allergic reactions. Insulin Glargine might cause low blood sugar, weight gain, injection site reactions, and swelling.

Eligibility Criteria

Inclusion Criteria

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to end of the study (approximately 104 weeks)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to end of the study (approximately 104 weeks)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to end of the study (approximately 104 weeks) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Time to First Occurrence of Any Major Adverse Cardiovascular Event (MACE-4) [Myocardial Infarction (MI), Stroke, Hospitalization for Unstable Angina, or Cardiovascular (CV) Death]

Secondary study objectives

Change from Baseline in Body Weight

Change from Baseline in Daily Average 7-point Self-monitoring Blood Glucose (SMBG) Profile

Change from Baseline in Fasting Serum Glucose

+6 more

Side effects data

From 2017 Phase 4 trial • 295 Patients • NCT02004366

Surgical Reintervention

Renal

Infections

Hematologic

Pulmonary

ICU admission

Gastrointestinal

100%

80%

60%

40%

20%

Study treatment Arm

Linagliptin In-hospital

Basal Bolus In-hospital

Linagliptin on Discharge

Linagliptin+50%Glargine Dose on d/c

Linagliptin+80%Glargine Dose on d/c

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: OrforglipronExperimental Treatment1 Intervention

Participants will receive escalated doses of orforglipron orally.

Group II: Insulin GlargineActive Control1 Intervention

Participants will receive insulin glargine subcutaneously (SC). Doses will be individualized and titrated according to a treat-to-target algorithm.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Orforglipron

2024

Completed Phase 1

~80

0 / 10Eligibility 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

Glucagon-like peptide-1 (GLP-1) receptor agonists, such as Orforglipron, work by mimicking the incretin hormone GLP-1, which is released after eating. These medications enhance insulin secretion, inhibit glucagon release, slow gastric emptying, and promote satiety, leading to reduced food intake and weight loss. This mechanism is particularly beneficial for obesity patients as it addresses both hyperglycemia and excess weight, improving overall metabolic health and reducing cardiovascular risk. Other common treatments for obesity include lifestyle modifications, pharmacotherapy with medications like phentermine-topiramate, and bariatric surgery, each targeting different aspects of weight management and metabolic improvement.