What side effects are associated with this type of intervention?

GLP-1 receptor agonists, such as liraglutide, exenatide, and semaglutide, commonly cause gastrointestinal side effects like nausea, vomiting, and diarrhea. There are also potential risks of thyroid C cell tumors and pancreatitis. SGLT2 inhibitors, like dapagliflozin, can lead to urinary tract infections, genital infections, and an increased risk of amputations.

What prior FDA approvals exist?

Several GLP-1 receptor agonists have been approved by the FDA for the treatment of Type 2 Diabetes. Liraglutide was approved based on its efficacy in improving glycemic control and its cardiovascular benefits. Exenatide, available in both twice-daily and extended-release formulations, has shown significant improvements in glycemic control and weight management. Dulaglutide, another once-weekly GLP-1 receptor agonist, has demonstrated similar benefits. These drugs are often used as adjuncts to metformin and have been shown to be effective in both adult and pediatric populations.

What other types of research exist?

Promising novel alternatives to Orforglipron for Type 2 Diabetes patients include other GLP-1 receptor agonists like semaglutide and dulaglutide, DPP-4 inhibitors such as sitagliptin and saxagliptin, and SGLT2 inhibitors like dapagliflozin and tofogliflozin. These alternatives have shown efficacy in improving glycemic control and have acceptable safety profiles.

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Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor

Orforglipron vs Dapagliflozin for Type 2 Diabetes (ACHIEVE-2 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 a clinical diagnosis of T2D based on the World Health Organization classification or other locally applicable diagnostic standards

Have been on stable diabetes treatment with metformin ≥1500 milligram per day (mg/day) during the 90 days prior to screening and maintained through randomization

Must not have

Have had chronic or acute pancreatitis any time

Have acute or chronic hepatitis

Timeline

Screening 3 weeks

Treatment 40 weeks

Follow Up week 40

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing two medications, orforglipron and dapagliflozin, to see which one better controls blood sugar in people with type 2 diabetes who are not well-managed on metformin alone. Orforglipron lowers blood sugar levels, while dapagliflozin helps remove sugar through urine. The study will last several months. Dapagliflozin has been shown to improve blood sugar control in various studies.

Who is the study for?

This trial is for adults with Type 2 Diabetes who haven't been able to control their blood sugar levels using metformin alone. Participants should be stable on their current metformin dose.

What is being tested?

The study compares the safety and effectiveness of a new diabetes medication, Orforglipron, with an existing one, Dapagliflozin. It aims to see which is better at controlling blood sugar over about 46 weeks.

What are the potential side effects?

Possible side effects may include urinary tract infections, dehydration, low blood pressure, kidney problems, increased cholesterol levels and hypersensitivity reactions.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with Type 2 Diabetes.

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I have been taking at least 1500 mg of metformin daily for the last 90 days.

Exclusion Criteria

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

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I have had pancreatitis before.

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I have hepatitis.

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I have Type 1 Diabetes.

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I have taken diabetes medication other than metformin in the last 90 days.

Timeline

Screening ~ 3 weeks2 visits

Treatment ~ 40 weeks12 visits

Follow Up ~ week 40

Screening ~ 3 weeks

Treatment ~ 40 weeks

Follow Up ~week 40

This trial's timeline: 3 weeks for screening, 40 weeks for treatment, and week 40 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Change from Baseline in Hemoglobin A1c: (HbA1c)

Secondary study objectives

Change from Baseline in Body Weight

Change from Baseline in Diabetes Treatment Satisfaction Questionnaire-Change (DTSQc) Scores

Change from Baseline in Diastolic Blood Pressure (DBP)

+13 more

Side effects data

From 2018 Phase 4 trial • 30 Patients • NCT03006471

20%

Cervicovaginal infection

13%

Urinary tract infections

100%

80%

60%

40%

20%

Study treatment Arm

Dapagliflozin

Placebo

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

4Treatment groups

Experimental Treatment

Active Control

Group I: Orforglipron Dose 3Experimental Treatment1 Intervention

Participants will receive orforglipron orally.

Group II: Orforglipron Dose 2Experimental Treatment1 Intervention

Participants will receive orforglipron orally.

Group III: Orforglipron Dose 1Experimental Treatment1 Intervention

Participants will receive orforglipron orally.

Group IV: DapagliflozinActive Control1 Intervention

Participants will receive dapagliflozin orally.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Orforglipron

2024

Completed Phase 1

~80

0 / 6Eligibility 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

GLP-1 receptor agonists, such as Orforglipron, mimic the incretin hormone GLP-1 to enhance insulin secretion, reduce glucagon release, slow gastric emptying, and increase satiety, thereby improving blood sugar control and aiding in weight loss. This multifaceted approach is vital for Type 2 Diabetes patients as it targets key issues like insulin resistance and beta-cell dysfunction. Other treatments, like metformin and SGLT2 inhibitors, work by decreasing hepatic glucose production and increasing insulin sensitivity or reducing glucose reabsorption in the kidneys, respectively. These mechanisms collectively help manage blood glucose levels and mitigate the risk of complications.

Cardiovascular effects of GLP-1 receptor agonism.Incretin therapies: highlighting common features and differences in the modes of action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors.