What is the mechanism of action of this treatment?

Incretin-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, enhance insulin secretion and inhibit glucagon release in response to meals, improving glycemic control and promoting weight loss. SGLT2 inhibitors reduce blood glucose by increasing urinary glucose excretion, which also aids in weight loss and lowers blood pressure. These mechanisms are crucial for Type 2 Diabetes patients as they address both hyperglycemia and obesity, common comorbidities that exacerbate the disease. Effective weight management and glycemic control can significantly reduce the risk of diabetes-related complications and improve overall health outcomes.

What side effects are associated with this type of intervention?

Common treatments for Type 2 Diabetes that focus on weight loss and glycemic control, such as pramlintide, semaglutide, and dapagliflozin, have several known side effects. Pramlintide is often associated with nausea, vomiting, anorexia, and hypoglycemia, particularly in the initial stages of treatment. Semaglutide can cause gastrointestinal issues, including nausea and vomiting, and may lead to weight regain if discontinued. Dapagliflozin's side effects include nonsevere hypoglycemia and a potential increase in urinary tract infections. These side effects are generally mild to moderate but should be monitored by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several GLP-1 receptor agonists for the treatment of Type 2 Diabetes, which also aid in weight loss. Notable approvals include liraglutide (brand name: Victoza) and extended-release exenatide (brand name: Bydureon BCise). Liraglutide was approved based on its efficacy in improving glycemic control and modest weight loss in pediatric patients, while exenatide showed significant improvements in glycemic control and was approved for once-weekly administration. Additionally, semaglutide (brand name: Ozempic) has been approved for its dual benefits in glycemic control and weight reduction. These treatments are similar to AMG 133 in their focus on weight loss induction and maintenance in patients with Type 2 Diabetes.

What other types of research exist?

Promising alternatives to AMG 133 for weight loss and glycemic control in Type 2 Diabetes patients include pramlintide, imeglimin, and GLP-1 receptor agonists like liraglutide and albiglutide. Pramlintide has shown combined improvements in glycemic and weight control. Imeglimin significantly improved HbA1c with a similar safety profile to placebo. GLP-1 receptor agonists, such as liraglutide and albiglutide, have demonstrated efficacy in reducing HbA1c and supporting weight loss.

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Monoclonal Antibodies

AMG 133 for Obesity With or Without Type 2 Diabetes

Phase 2

Waitlist Available

Research Sponsored by Amgen

Eligibility Criteria Checklist

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

Must have

Age ≥18 years at the time of signing informed consent.

BMI ≥30 kg/m^2, or ≥27 kg/m^2 and previous diagnosis with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease.

Must not have

Family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN-2).

History of pancreatitis.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline and week 52

Awards & highlights

Summary

This trial is testing AMG 133, a new drug, to see if it helps people lose weight and keep it off. It targets overweight or obese individuals, both with and without Type 2 diabetes. The drug may work by affecting metabolism or appetite.

Who is the study for?

Adults over 18 with obesity or overweight, who've tried and failed to lose weight through diet. Cohort A includes those without diabetes; Cohort B includes those with Type 2 diabetes, managed by diet/exercise or certain medications. Excluded are individuals with weight changes >5kg in the last 3 months, specific psychiatric disorders, history of pancreatitis, or genetic conditions like MEN-2.

What is being tested?

The trial is testing three doses of AMG 133 against a placebo to see which dose is best at helping adults lose weight and maintain that loss over a year. It's divided into two groups: one for people just overweight/obese (Cohort A) and another for those also dealing with Type 2 diabetes (Cohort B).

What are the potential side effects?

While not specified here, similar drugs often cause digestive issues like nausea or diarrhea, potential low blood sugar in diabetics, injection site reactions if it's an injectable drug, and sometimes headaches or fatigue.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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My BMI is over 30, or it's over 27 and I have a condition like high blood pressure or heart disease.

Exclusion Criteria

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

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I have a history of medullary thyroid cancer or MEN-2 in my family or myself.

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I have had pancreatitis before.

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My obesity is caused by a hormone-related condition.

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I have been diagnosed with major depression in the past 2 years.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline and week 52

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline and week 52

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline and week 52 for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Change from Baseline to Week 52 in Body Fat Mass Using Dual-energy X-ray Absorptiometry (DEXA)

Change from Baseline to Week 52 in Lean Body Mass Using DEXA

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: Cohort B: Maridebart CafraglutideExperimental Treatment2 Interventions

Part 1: Cohort B will consist of participants with a diagnosis of type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 4 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.

Group II: Cohort A: Maridebart CafraglutideExperimental Treatment2 Interventions

Part 1: Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 7 dose cohorts. Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.

Group III: Cohort A: PlaceboPlacebo Group2 Interventions

Part 1: Cohort A will consist of participants without a diagnosis of type 1 or type 2 diabetes mellitus. Participants will be randomized to receive maridebart cafraglutide or placebo in 1 of 7 dose cohorts . Participants will then have the option to begin part 2 if they meet the entry criteria. Part 2: Participants that continue into part 2 will be re-randomized to receive maridebart cafraglutide or Placebo in 1 of 4 dose cohorts.

Group IV: Cohort B: PlaceboPlacebo Group2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo

1995

Completed Phase 3

~2670

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

Incretin-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, enhance insulin secretion and inhibit glucagon release in response to meals, improving glycemic control and promoting weight loss. SGLT2 inhibitors reduce blood glucose by increasing urinary glucose excretion, which also aids in weight loss and lowers blood pressure. These mechanisms are crucial for Type 2 Diabetes patients as they address both hyperglycemia and obesity, common comorbidities that exacerbate the disease. Effective weight management and glycemic control can significantly reduce the risk of diabetes-related complications and improve overall health outcomes.

Effect of electroacupuncture on glucose and lipid metabolism in type 2 diabetes: A protocol for systematic review and meta-analysis.Incretin therapies: highlighting common features and differences in the modes of action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors.Potential for combination of dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors for the treatment of type 2 diabetes.