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Update on AMG-133 for Weight Loss

AMG 133 for Weight Loss

AMG-133 is an investigational molecule under development by the pharmaceutical company Amgen. It shows potential in treating obesity, a serious disease with long-term health complications. Approximately 74 percent of adults are considered overweight or obese, making new treatment options for this condition an exciting prospect. This article will discuss AMG-133 and its potential for weight loss.

What is AMG-133?

AMG-133 is a molecule with two distinct mechanisms. First, it acts as an antagonist of the glucose-dependent insulinotropic polypeptide receptor, also known as GIPR. Secondly, it works as an agonist of the glucagon-like peptide-1 (GLP-1) receptor. Via these mechanisms, AMG-133 works similarly to GLP-1 but opposes the effects of glucose-dependent insulinotropic polypeptide (GIP). When AMG-133 works synergistically on these two pathways, it is expected to improve weight loss and metabolic outcomes1.

How is AMG-133 being studied?

Amgen evaluated the weight loss potential of AMG-133 in a randomized, double-blind, placebo-controlled phase one study. The clinical trial compared the effects of AMG-133 versus placebo in individuals with a Body Mass Index (BMI) of at least 30 kg/m2. The objective of this study was to characterize the dose and safety profile of the medication1. Amgen has begun recruiting for its next phase 2 trial with AMG-133, which will aim to understand AMG-133's efficacy in more patients over a longer period of time2.

What were the results of the Phase 1 study?

The clinical trial showed that across the multiple ascending doses (MAD) group of participants, subjects lost an average of 14.5 percent of their body weight at the maximum dose of 420 mg. These results are similar to current marketed treatments being studied in obesity such as Wegovy (semaglutide) and Mounjaro (tirzapetide)3.

How may AMG-133 offer improvements over currently available therapy?

The current standard of care is Wegovy, which requires weekly administration. Weekly administration may lead to patients being noncompliant, as they have to frequently remember to take their medication. AMG-133, on the other hand, is administered every four weeks. This less frequent treatment schedule is more convenient for patients.

Additionally, overweight and obese patients commonly have comorbidities, such as high blood pressure, heart disease, and diabetes. When patients are balancing multiple conditions and diseases at once, it can be difficult to manage the multitude of medications. A less frequent dosing schedule would provide further convenience and increase compliance in these patients3.

What is next for AMG-133?

While the efficacy and safety of AMG-133 has not been fully established, future clinical trials will continue to evaluate its potential in the weight loss space. Amgen expects the upcoming phase 2 trial to begin early this year.


The prevalence and severity of obesity remains a major public health concern. Likewise, there is a significant need for effective therapies that target weight loss. AMG-133 represents a promising new molecule that has demonstrated early safety and efficacy in phase 1 trials. Time will tell if it can stand up to or supersede the currently available weight loss drugs on the market.



  1. https://www.amgen.com/newsroom/press-releases/2022/12/amgen-presents-new-amg-133-phase-1-clinical-data-at-wcirdc-2022
  2. https://clinicaltrials.gov/ct2/show/NCT05669599?term=amg-133&draw=2&rank=2
  3. https://www.pharmaceutical-technology.com/comment/amg-133-obesity-therapies/
David Bauder David J. Bauder, PA-C David Bauder, PA-C, is a certified physician assistant and the assistant medical director at Weight Loss and Vitality in Manassas and Alexandria, Virginia, Washington, DC; and Gaithersburg, MD. He enjoys helping patients optimize their physical and mental health to improve their overall well-being. He earned his physician assistant degree from the University of Texas Health Science Center at San Antonio. Afterward, he gained admission into the reputable graduate program for physician assistant studies at the University of Nebraska Health Science Center in Omaha. David has over 26 years of experience working as a physician assistant. He’s practiced in podiatry, family medicine, emergency medicine, general surgery, urgent care, and functional medicine.

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