What is the mechanism of action of this treatment?

Common treatments for Endometrial Hyperplasia include Semaglutide and the Levonorgestrel intrauterine device (LNG-IUD). Semaglutide, a GLP-1 receptor agonist, enhances insulin secretion, inhibits glucagon release, and slows gastric emptying, which helps manage obesity and diabetes—key risk factors for Endometrial Hyperplasia. The LNG-IUD releases progestin locally within the uterus, counteracting estrogen's proliferative effects on the endometrium and reducing hyperplasia. These treatments are significant for patients as they address both the underlying risk factors and directly reduce endometrial proliferation, thereby managing and potentially reversing hyperplasia.

What side effects are associated with this type of intervention?

Common treatments for endometrial hyperplasia include the Levonorgestrel intrauterine device (LNG-IUD) and GLP-1 receptor agonists like Semaglutide. The LNG-IUD, which releases progestin, can cause side effects such as irregular bleeding, headaches, breast tenderness, and mood changes. Semaglutide, a GLP-1 receptor agonist, may lead to gastrointestinal issues like nausea, vomiting, diarrhea, and constipation, as well as potential risks of pancreatitis and gallbladder disease. Both treatments are generally well-tolerated but should be discussed with a healthcare provider to weigh the benefits and risks.

What prior FDA approvals exist?

The FDA has approved the use of Levonorgestrel-releasing intrauterine devices (LNG-IUD) for the treatment of endometrial hyperplasia, as they release progestin to reduce hyperplasia. While Semaglutide, a GLP-1 receptor agonist, is primarily approved for diabetes and weight management, it is being studied for its potential benefits in endometrial hyperplasia due to its effects on weight loss and metabolic improvements. Other FDA-approved treatments for endometrial hyperplasia include oral progestins and combined estrogen-progestin oral contraceptives.

What other types of research exist?

Promising novel alternatives for treating Endometrial Hyperplasia in 2024 include Dienogest, a progestogenic drug with moderate estrogen suppression, anti-inflammatory, antiproliferative, and antiangiogenic properties, and Gonadotropin-releasing hormone (GnRH) analogs, which are highly effective at suppressing ovarian hormone production and inhibiting the growth of endometrial tissue. These alternatives offer effective management of endometrial hyperplasia with different mechanisms of action compared to Semaglutide and LNG-IUD.

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GLP-1R Agonist

Drug + IUD & Weight Intervention for Hyperplasia

Phase 2

Waitlist Available

Led By Andrea R Hagemann, M.D., MSCI

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

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

Must have

Be between 18 and 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at enrollment, 12 months, and end of treatment (estimated to be 2 years)

Summary

This trial tests if using semaglutide and an LNG-IUD together can help premenopausal women with thickened uterine linings keep their uterus, lose weight, and improve their quality of life. The levonorgestrel intrauterine device (LNG-IUD) has been used effectively for various conditions including thickened uterine linings, heavy menstrual bleeding, and as part of hormone replacement therapy.

Who is the study for?

This trial is for premenopausal women aged 18-45 with obesity (BMI ≥ 30 kg/m2) and complex atypical endometrial hyperplasia who want to preserve their uterus. They must not have used GLP-1R agonists recently, have a history of certain diseases like MEN 2 or MTC, uncontrolled illnesses, renal dysfunction, or be pregnant/breastfeeding.

What is being tested?

The study tests if semaglutide combined with a levonorgestrel intrauterine device (LNG-IUD) is more effective than LNG-IUD alone in preserving the uterus and aiding weight loss in women with endometrial hyperplasia. It also examines the impact on quality of life.

What are the potential side effects?

Semaglutide may cause digestive issues, risk of pancreatitis, changes in blood sugar levels, and possible thyroid tumors. The LNG-IUD could lead to menstrual changes or discomfort where it's placed.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at enrollment, 12 months, and end of treatment (estimated to be 2 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at enrollment, 12 months, and end of treatment (estimated to be 2 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and at enrollment, 12 months, and end of treatment (estimated to be 2 years) 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 in Cancer Worry Impact of Events Scale (CWIES)

Change in Impact of Weight on Quality of Life (IWQOL-Lite)

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm 1: Semaglutide + progestinExperimental Treatment3 Interventions

* The progestin will be delivered via the levonorgestrel-releasing IUD and it is standard of care. * Will receive injectable pens containing semaglutide and will be self-administered on a weekly basis for up to 104 weeks. Dosing will be escalated during weeks 1 through 16 (start at 0.24 mg up to 2.4 mg). * Will be enrolled in a behavioral weight program that is optional to attend. The program will be delivered in a closed-group format. The group program will consist of 12 consecutive 60 minute weekly visits, and will recur every three months such that participants can join the soonest available Week 1 session after study enrollment. Each group session will focus on providing education and cognitive/behavioral strategies to achieve a healthier, reduced-calorie diet and a more physically active lifestyle. Cognitive/behavioral strategies will consist of goal setting, problem solving, cognitive restructuring, stimulus control, and stress management.

Group II: Arm 2: Placebo + ProgestinActive Control3 Interventions

* The progestin will be delivered via the levonorgestrel-releasing IUD and it is standard of care. * Will receive injectable pens containing the placebo and will be self-administered on a weekly basis for up to 104 weeks. * Will be enrolled in a behavioral weight program that is optional to attend. The program will be delivered in a closed-group format. The group program will consist of 12 consecutive 60 minute weekly visits, and will recur every three months such that participants can join the soonest available Week 1 session after study enrollment. Each group session will focus on providing education and cognitive/behavioral strategies to achieve a healthier, reduced-calorie diet and a more physically active lifestyle. Cognitive/behavioral strategies will consist of goal setting, problem solving, cognitive restructuring, stimulus control, and stress management.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Semaglutide

2021

Completed Phase 4

~5160

Do I qualify?Apply below to find out

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

Common treatments for Endometrial Hyperplasia include Semaglutide and the Levonorgestrel intrauterine device (LNG-IUD). Semaglutide, a GLP-1 receptor agonist, enhances insulin secretion, inhibits glucagon release, and slows gastric emptying, which helps manage obesity and diabetes—key risk factors for Endometrial Hyperplasia. The LNG-IUD releases progestin locally within the uterus, counteracting estrogen's proliferative effects on the endometrium and reducing hyperplasia. These treatments are significant for patients as they address both the underlying risk factors and directly reduce endometrial proliferation, thereby managing and potentially reversing hyperplasia.

Route-specific association of progestin therapy and concurrent metformin use in obese women with complex atypical hyperplasia.Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial.