What side effects are associated with this type of intervention?

Common treatments for Type 2 Diabetes, such as GLP-1 receptor agonists (e.g., liraglutide, exenatide) and insulin therapy, have known side effects. GLP-1 receptor agonists can cause gastrointestinal symptoms like nausea and vomiting, and there is a potential risk of pancreatitis and pancreatic cancer. Insulin therapy can lead to hypoglycemia and weight gain. Metformin, another common treatment, may cause gastrointestinal issues and, rarely, lactic acidosis. SGLT2 inhibitors can lead to urinary tract infections and genital infections. These side effects should be discussed with a healthcare provider to tailor the best treatment plan for individual patients.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Type 2 Diabetes that modulate glucagon or insulin pathways. GLP-1 receptor agonists, such as liraglutide, exenatide, dulaglutide, and semaglutide, enhance glucose-dependent insulin secretion, delay gastric emptying, and regulate postprandial glucagon. These drugs have shown efficacy in improving glycemic control and, in some cases, promoting weight loss. Additionally, dual agonists like tirzepatide, which target both GIP and GLP-1 receptors, are in development and have shown promising results in clinical trials. These treatments are similar to glucagon receptor antagonists in their aim to manage the effects of elevated plasma glucagon concentrations in Type 2 Diabetes.

What other types of research exist?

Promising novel alternatives to Glucagon Receptor Antagonists for Type 2 Diabetes patients include: <ol> <li>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as liraglutide, semaglutide, and dulaglutide, which improve glucose-dependent insulin release, slow gastric emptying, and regulate postprandial glucagon.</li> <li></li> </ol> Dual GLP-1/glucagon receptor agonists like SAR425899, which have shown efficacy in improving postprandial glucose metabolism. 3. Dipeptidyl peptidase-4 (DPP-4) inhibitors such as sitagliptin and linagliptin, which increase insulin release in a glucose-dependent manner and have a favorable safety profile. 4. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, which reduce glucose reabsorption in the kidneys and have demonstrated cardiovascular benefits.

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Glucagon Receptor Antagonist

REMD-477 for Type 2 Diabetes

Q: What is the mechanism of action of this treatment?

Glucagon receptor antagonists and GLP-1 receptor agonists are common treatments for Type 2 Diabetes (T2D) that target different aspects of glucose metabolism. Glucagon receptor antagonists block the glucagon receptor, reducing the effects of elevated plasma glucagon concentrations, which helps lower blood glucose levels by inhibiting gluconeogenesis and glycogenolysis in the liver. GLP-1 receptor agonists enhance glucose-dependent insulin secretion, delay gastric emptying, regulate postprandial glucagon, and reduce food intake, thereby improving glycemic control and aiding in weight loss. These mechanisms are crucial for managing blood sugar levels and overall metabolic health in T2D patients.

Phase < 1

Waitlist Available

Led By Ralph DeFronzo, MD

Research Sponsored by The University of Texas Health Science Center at San Antonio

Eligibility Criteria Checklist

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

Must have

Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate contraceptive precautions (i.e. oral contraceptives, approved hormonal implant, intrauterine device, diaphragm with spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal ligation, bilateral oophorectomy)

Type 2 diabetic subjects, males/females, age = 18-70 years, BMI = 25-40 kg/m2, HbA1c = 7.5-10.0%

Must not have

Patients must not have received a thiazolidinedione, GLP-1 agonist, or insulin for more than one week during the year prior to randomization

Patients with a history of clinically significant heart disease (New York Heart Classification greater than class 2; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to 13 weeks

Summary

This trial tests a new drug that blocks glucagon, a hormone that raises blood sugar. It targets Type 2 Diabetes patients whose blood sugar is not well-controlled with current treatments. The drug aims to lower and stabilize blood sugar levels by preventing glucagon from working.

Who is the study for?

This trial is for Type 2 diabetes patients aged 18-70 with a BMI of 25-40 kg/m2 and HbA1c levels between 7.5-10%. Participants must be on stable diabetes medication, if any, for at least three months. Women must use contraception or be post-menopausal/surgically sterilized. Exclusions include major organ disease, significant heart/pulmonary issues, psychiatric disturbances, recent weight fluctuation, certain medications affecting insulin sensitivity, and contraindications to MRI.

What is being tested?

The study tests REMD-477's effects on glucose tolerance and insulin sensitivity in liver, muscle, adipocytes (fat cells), beta cell function (insulin-producing cells), and inflammation in fat tissue among T2DM patients. It compares the drug against a placebo through subcutaneous injections to evaluate its potential benefits.

What are the potential side effects?

Potential side effects are not explicitly listed but may include reactions at the injection site due to subcutaneous administration of REMD-477 or placebo. As with many drugs targeting metabolic processes, there could also be risks related to blood sugar levels and possible allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

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I am a woman not breastfeeding, either post-menopausal, using birth control, or sterilized.

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I am between 18-70 years old, have Type 2 diabetes, my BMI is between 25-40, and my HbA1c is between 7.5-10%.

Select...

I have been on the same diabetes medication dose for at least 3 months.

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I have Type 2 Diabetes and am either not on medication or only take metformin, sulfonylureas, or SGLT-2 inhibitors.

Select...

I can communicate clearly and can legally consent to participate.

Exclusion Criteria

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

Select...

I haven't used certain diabetes medications for more than a week in the last year.

Select...

I do not have serious heart, blood vessel, or lung problems.

Select...

I or my family have a history of specific pancreatic or endocrine tumors.

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I am unable to give my written consent voluntarily.

Select...

I do not have any major organ diseases as per my recent tests and exams.

Select...

I have not been treated with GLP-1 receptor agonists or insulin.

Select...

I do not have type 1 diabetes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to 13 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to 13 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to 13 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

Fasting Plasma glucose (FPG)

Glycated Hemoglobin (HbA1c)

Hepatic insulin sensitivity

+4 more

Side effects data

From 2021 Phase 2 trial • 154 Patients • NCT03117998

16%

Upper respiratory tract infection

16%

Headache

12%

Aspartate aminotransferace increased

12%

Nausea

12%

Alanine aminotransferace increased

Hypoglycaemia

Anemia

Cough

Diarrhoea

Oropharyngeal pain

Vomiting

100%

80%

60%

40%

20%

Study treatment Arm

Part A - 35 mg REMD-477

Part A - 70 mg REMD-477

Part A - Matching Placebo

Part B - 35 mg REMD-477

Part B - 70 mg REMD-477

Part B - Matching Placebo

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Glucagon Receptor Agonist (GRA) REMD-477 groupExperimental Treatment1 Intervention

Participants are assigned to a 12 week treatment of REMD-477

Group II: Placebo groupPlacebo Group1 Intervention

Participants are assigned to a 12 week course of placebo for REMD-477

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

REMD-477

2021

Completed Phase 2

~270

0 / 12Eligibility 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 receptor antagonists and GLP-1 receptor agonists are common treatments for Type 2 Diabetes (T2D) that target different aspects of glucose metabolism. Glucagon receptor antagonists block the glucagon receptor, reducing the effects of elevated plasma glucagon concentrations, which helps lower blood glucose levels by inhibiting gluconeogenesis and glycogenolysis in the liver. GLP-1 receptor agonists enhance glucose-dependent insulin secretion, delay gastric emptying, regulate postprandial glucagon, and reduce food intake, thereby improving glycemic control and aiding in weight loss. These mechanisms are crucial for managing blood sugar levels and overall metabolic health in T2D patients.

[Glucagon antagonists open a new way in treatment of type 2 diabetes Mellitus].What next after basal insulin? Treatment intensification with lixisenatide in Asian patients with type 2 diabetes mellitus.