Metformin Plus IUD Well-Tolerated in EIN/Endometrial Cancer
- Seattle, WA (2025-03-16) – new research presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO) indicates that metformin, a common antidiabetic drug, may...
- The study focused on the combination of metformin with standard of care levonorgestrel-releasing (LR) intrauterine devices (IUD).
- The overall complete response (CR) rate at 6 months was 80% (95% CI, 52%-96%) among all efficacy-evaluable patients.
Metformin Shows Promise in Endometrial Cancer treatment
Table of Contents
- Metformin Shows Promise in Endometrial Cancer treatment
- Metformin and Endometrial Cancer: Q&A on Promising New Research
- Key Questions About Metformin and Endometrial Cancer Treatment
- 1.What is the main finding of the study on metformin and endometrial cancer?
- 2. What is EIN and EC?
- 3. What were the complete response (CR) rates observed in the study?
- 4. How does the metformin and LR-IUD combination compare to LR-IUD alone?
- 5. Who are the ideal candidates for this combined treatment approach?
- 6. What were the key components of the study protocol?
- 7. What were the most common adverse effects observed in the study?
- 8. How important was adherence to the treatment protocol?
- 9. What factors might influence the response to treatment?
- 10. What are the future research directions suggested by the investigators?
- 11. Study Patient Demographics.
- 12. Where was this research presented?
- Key Questions About Metformin and Endometrial Cancer Treatment
Seattle, WA (2025-03-16) – new research presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO) indicates that metformin, a common antidiabetic drug, may offer a well-tolerated and effective non-surgical treatment option for patients with endometrial intraepithelial neoplasia (EIN) and endometrial cancer (EC).
Metformin and LR-IUD Combination: A Potential Breakthrough
The study focused on the combination of metformin with standard of care levonorgestrel-releasing (LR) intrauterine devices (IUD). The results suggest a promising avenue for patients seeking fertility preservation or those with surgical risks.
Efficacy data revealed encouraging results. The overall complete response (CR) rate at 6 months was 80% (95% CI, 52%-96%) among all efficacy-evaluable patients. Specifically, the CR rates were 100% (95% CI, 66%-100%) in the EIN group and 40% (95% CI, 5%-85%) in the EC group.Furthermore, the CR rate at 12 months among all patients reached 87.5% (95% CI, 62.0%-98.0%).
The addition of metformin to standard LR-IUD therapy is a well-tolerated combination with potential activity in EIN and EC.
Jennifer Haag, MD, fellow of gynecologic Oncology of the Department of Obstetrics and Gynecology at UNC Health
Dr. Haag further noted, “Our study demonstrated [a] slightly higher CR rate [with] metformin plus LR-IUD compared with prior studies of LR-IUD alone. This combination is worthy of continued exploration in patients desiring fertility preservation or those with comorbidities prohibitive to surgery, as few other options currently exist.”
Study Details and Patient Demographics
The trial enrolled patients with biopsy-proven EIN or grade 1 EC who desired fertility preservation or faced unacceptable surgery risks. The study protocol involved MRI for EC patients,followed by dilation and curettage (D&C) with LR-IUD placement and the initiation of metformin dosing for both groups.
Patients underwent concurrent Eosin-Methylene Blue (EMB) agar testing, along with evaluations for adverse effects (AE) and adherence. Patients showing disease progression or experiencing a qualifying AE were removed from the protocol. Those with a CR, regression, or stable disease continued treatment with metformin plus LR-IUD for up to 12 months.
The primary endpoint was the 6-month CR rate in the overall population. Secondary endpoints included the 6-month CR rate in the EIN and EC groups separately, the 12-month CR rate in the overall population, adherence rates, and AE incidence. The study aimed to assess the response and safety of metformin with standard LR-IUD in EIN and EC, evaluating its impact on CR rates by potentially reversing progestin resistance.
key Patient Characteristics
- Among 15 evaluable patients at 6 months:
- Median age: 41.4 years (SD, 16.8)
- Median body mass index (BMI): 55.2 kg/m2 (range, 30.4-80.9)
- 75% were White
- Responders to treatment (n = 12):
- Median age: 31.0 years
- 83% were White
- Median BMI: 55.2 kg/m2 at baseline
- Non-responders to treatment (n = 3):
- Median age: 35.0 years
- 100% were White
- Median BMI: 55.6 kg/m2 at baseline
Adherence, Diabetes, and Pathology
Among responders, 8.3% had diabetes at diagnosis, while 33.3% of non-responders had diabetes. Adherence of 80% or greater was observed in 83% of responders and 100% of non-responders. The primary reason for avoiding surgery was fertility preservation in 66.7% of both groups, while unacceptable surgical risk accounted for 25.0% of responders and 33.3% of non-responders.
The most common pathology among responders was EIN (66.7%), whereas EC was most common among non-responders (100%).
Adverse Effects
The most common any-grade AEs observed during the trial included diarrhea (55%), nausea (55%), transaminitis (15%), anorexia (15%), and headache (15%). Singular instances of grade 3 diarrhea, vomiting, and renal calculus were also reported.
Future Research Directions
Investigators suggest that future research should focus on evaluating metabolic markers to predict clinical response to treatment. Additionally, they propose exploring the combination of LR-IUD with weight loss strategies, including GLP-1 agonists, to optimize weight loss and improve treatment outcomes.
Reference
Haag J, moore D, Schuler K, Doll K, Bae-Jump V. Metformin with the levonorgestrel-releasing intrauterine device for the treatment of endometrial intraepithelial neoplasia and endometrial cancer in non-surgical patients. Presented at the 2025 Society of Gynecologic Oncology Annual Meeting on women’s Cancer (SGO); Seattle, WA, march 14-17, 2025.
Metformin and Endometrial Cancer: Q&A on Promising New Research
This article explores the latest research on using metformin, in combination with a levonorgestrel-releasing intrauterine device (LR-IUD), as a potential treatment for endometrial intraepithelial neoplasia (EIN) and endometrial cancer (EC). The findings, presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO), offer hope for patients desiring fertility preservation or those with surgical risks.
Key Questions About Metformin and Endometrial Cancer Treatment
1.What is the main finding of the study on metformin and endometrial cancer?
The study suggests that the combination of metformin and a levonorgestrel-releasing intrauterine device (LR-IUD) is a well-tolerated and potentially effective non-surgical treatment option for patients with endometrial intraepithelial neoplasia (EIN) and endometrial cancer (EC), particularly for those who wish to preserve fertility or who are not good candidates for surgery.
2. What is EIN and EC?
EIN: Endometrial Intraepithelial Neoplasia, a precancerous condition of the uterine lining.
EC: Endometrial Cancer, cancer of the uterine lining.
3. What were the complete response (CR) rates observed in the study?
Overall (6 months): 80% (95% CI, 52%-96%)
EIN Group (6 months): 100% (95% CI, 66%-100%)
EC Group (6 months): 40% (95% CI, 5%-85%)
Overall (12 months): 87.5% (95% CI,62.0%-98.0%)
4. How does the metformin and LR-IUD combination compare to LR-IUD alone?
According to Dr.Jennifer Haag, the study demonstrated a slightly higher complete response rate with metformin plus LR-IUD compared to prior studies using LR-IUD alone. This suggests a potential benefit of adding metformin to the standard LR-IUD therapy.
5. Who are the ideal candidates for this combined treatment approach?
The combination of metformin and LR-IUD is particularly relevant for:
Patients with biopsy-proven EIN or grade 1 EC.
Those who desire fertility preservation.
Patients who face unacceptable risks associated with surgery, or have comorbidities prohibitive to surgery.
6. What were the key components of the study protocol?
The study protocol included:
MRI for EC patients
Dilation and curettage (D&C) with LR-IUD placement
initiation of metformin dosing for both EIN and EC groups.
Concurrent Eosin-Methylene Blue (EMB) agar testing
Regular evaluations for adverse effects (AE) and adherence.
7. What were the most common adverse effects observed in the study?
The most common adverse effects (any grade) included:
Diarrhea (55%)
Nausea (55%)
Transaminitis (15%)
Anorexia (15%)
Headache (15%)
Singular instances of grade 3 diarrhea, vomiting, and renal calculus were also reported.
8. How important was adherence to the treatment protocol?
Adherence to the treatment protocol was high, particularly among those who responded to treatment. 83% of responders showed adherence of 80% or greater, and 100% of non-responders showed adherence of 80% or greater.
9. What factors might influence the response to treatment?
The study suggests that diabetes status and pathology may influence treatment response.
A higher percentage of non-responders had diabetes at diagnosis compared to responders (33.3% vs.8.3%).
EIN was more common among responders (66.7%), while EC was most common among non-responders (100%).
10. What are the future research directions suggested by the investigators?
The investigators suggest that future research should focus on:
Evaluating metabloic markers to predict clinical response to treatment
* Exploring the combination of LR-IUD with weight loss strategies,including GLP-1 agonists,to optimize weight loss and improve treatment outcomes.
11. Study Patient Demographics.
| Characteristic | All Evaluable | Responders | Non-Responders |
| :———————– | :————– | :—————- | :—————- |
| Median Age (years) | 41.4 | 31.0 | 35.0 |
| Median BMI (kg/m^2) | 55.2 | 55.2 | 55.6 |
| White (%) | 75% | 83% | 100% |
| Diabetes (%) (responders V non responders) | N/A | 8.3% | 33.3% |
| Most Common Pathology | N/A | EIN (66.7%) | EC (100%) |
12. Where was this research presented?
The research was presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO) in Seattle, WA, March 14-17, 2025.