Metformin Response During Meal Test for Type 2 Diabetes

(SCRAMBLED EGGS Trial)

Overseen By Cristina Quintero

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Diabetes medications, Glucocorticoids

Disqualifiers: Liver disease, Renal impairment, others

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how specific genes, such as SLC16A11, influence the response of people with type 2 diabetes to food and metformin, a common diabetes medication. Participants will consume a specially prepared meal and take metformin to determine if their body's responses vary based on genetic makeup. The trial includes two groups: one with the gene variant and another without. It suits adults who aren't currently taking diabetes medication and can consume a meal containing protein, carbohydrates, and fat. As an unphased trial, this study offers a unique opportunity to contribute to genetic research that may enhance future diabetes treatment.

Will I have to stop taking my current medications?

If you are currently taking any medications for diabetes or medications that affect blood sugar levels, you will need to stop taking them to participate in this study. The trial does not specify other medications, but planned changes to certain prescribed medications, like diuretics, are not allowed during the study.

Is there any evidence suggesting that metformin is likely to be safe for humans?

Research shows that metformin is a well-researched and commonly used medicine for treating type 2 diabetes. Studies have found that it is generally safe and most people tolerate it well. Common side effects include an upset stomach, nausea, and diarrhea, but these usually improve over time.

Metformin has been used safely to treat diabetes for many years. It also offers benefits like improving heart health and aiding in weight loss. Serious side effects, such as lactic acidosis—a rare but serious condition where too much lactic acid builds up in the blood—are uncommon.

Overall, metformin is considered a safe choice for many people with type 2 diabetes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how genetic differences, specifically the presence of the SLC16A11 risk allele, may affect the response to metformin, a common treatment for type 2 diabetes. Unlike standard treatments, which are generally applied universally, this approach could lead to more personalized diabetes management. By understanding how carriers of this allele respond to metformin compared to non-carriers, the trial aims to tailor treatments to individual genetic profiles, potentially improving efficacy and minimizing side effects.

What evidence suggests that metformin might be an effective treatment for type 2 diabetes?

Research has shown that metformin effectively treats type 2 diabetes by lowering blood sugar levels, even with small doses like 500 mg. In adults at high risk, metformin can reduce the chance of developing type 2 diabetes by about 23%. The Diabetes Prevention Program found that its benefits last for many years. Overall, metformin is a well-established and reliable treatment for managing blood sugar in type 2 diabetes.

In this trial, participants will divide into two groups: carriers of the SLC16A11 risk allele and non-carriers. Both groups will undergo a Mixed Meal Tolerance Test on Day 1 and Day 8, with metformin administered between these tests to assess its impact. ^{6 7 8 9 10}

Who Is on the Research Team?

Laura N Brenner, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-79 who can consent to genetic research. It's not for those with kidney issues, contraindications to metformin, recent or planned medication changes, other study participation, intestinal malabsorption conditions, liver disease, pregnancy risk, or on diabetes medications.

Inclusion Criteria

I am an adult and not pregnant.

I am willing to consent to genetic testing.

Exclusion Criteria

I have a condition like celiac disease or had surgery that affects how my body absorbs food.

I am not pregnant, nursing, or at risk of becoming pregnant.

Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Assessment

Participants undergo a Mixed Meal Tolerance Test to assess baseline glucose and insulin response

1 day

1 visit (in-person)

Treatment

Participants receive 500mg metformin twice daily from Day 3 to Day 7

5 days

Daily medication administration

Post-Treatment Assessment

Participants undergo a Mixed Meal Tolerance Test in the presence of Metformin to assess changes in glucose and insulin response

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The study tests how genes affect responses to a special meal and metformin (a common diabetes drug). Participants will eat a mixed meal and take metformin while researchers observe differences in response between gene carriers linked to type 2 diabetes.

How Is the Trial Designed?

Group I: Carriers of the SLC16A11 risk allele Active Control 2 Interventions

Day 1: Mixed Meal Tolerance Test Day 3-7: 500mg metformin, twice daily Day 8: Mixed Meal Tolerance Test in presence of Metformin

Group II: Non-carriers of the SLC16A11 risk allele Placebo Group 2 Interventions

Day 1: Mixed Meal Tolerance Test Day 3-7: 500mg metformin, twice daily Day 8: Mixed Meal Tolerance Test in presence of Metformin

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Instituto Carlos Slim de la Salud

Collaborator

Trials

1

Recruited

1,000+

Broad Institute of MIT and Harvard

Collaborator

Trials

21

Recruited

16,300+

Broad Institute

Collaborator

Trials

21

Recruited

16,300+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12295976/

Metformin's Overall Effectiveness and Combined Action with ... Results: Overall, metformin may reduce the incidence of T2DM by 23% in high-risk adults (OR 0.77, 95% CI 0.67, 0.88, p-value 0.0001) and 25% in ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0002934397002544

Efficacy of Metformin in Type II Diabetes: Results of a ... Metformin lowered fasting plasma glucose and HbA 1c generally in a dose-related manner. Benefits were observed with as little as 500 mg of metformin.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2200433

Glycemia Reduction in Type 2 Diabetes — Glycemic ... All four medications, when added to metformin, decreased glycated hemoglobin levels. However, glargine and liraglutide were significantly, albeit modestly, ...

4. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.15663

Metformin: Therapeutic profile in the treatment of type 2 diabetes The extended Diabetes Prevention Program found that metformin remained effective throughout 21 years of follow-up (Diabetes Prevention Program ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9428832/

Efficacy of metformin in type II diabetes: results of a double- ... Conclusions: Metformin lowered fasting plasma glucose and HbA1c generally in a dose-related manner. Benefits were observed with as little as 500 mg of ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/metformin-oral-route/description/drg-20067074

Metformin (oral route) - Side effects & dosage Metformin is used to treat high blood sugar levels that are caused by a type of diabetes mellitus or sugar diabetes called type 2 diabetes.

7. vionausa.com vionausa.com/wp-content/uploads/2020/01/SDS-Metformin-HCl-ER-Tablets.pdf

SAFETY DATA SHEET Metformin Hydrochloride Extended ... Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial.

8. fda.gov fda.gov/media/181843/download

Riomet Pediatric Postmarketing Safety Review The safety and effectiveness of RIOMET ER as an adjunct to diet and exercise to improve glycemic control in pediatric patients 10 years of age ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK518983/

Metformin - StatPearls - NCBI Bookshelf - NIH Metformin is considered a safe and inexpensive medication that offers cardioprotective benefits and aids in weight loss, making it a valuable ...

10. hcp.merckgroup.com hcp.merckgroup.com/en/cmc/diabetes/products/glucophage-xr/safety-and-tolerability-profile.html

Glucophage® XR | Safety and Tolerability Profile Data from 3556 patients treated with once-daily Glucophage® XR for 12 ... Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes.