GLP-1A + Metformin + Mediterranean Diet for Prediabetes

Overseen By Jasmine Yang, BA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Stanford University

Must not be taking: Antihyperglycemics, Diabetogenics, Weight loss

Disqualifiers: CVD, Malignancy, Kidney/liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently taking medications for blood sugar control, weight loss, or those that could affect blood sugar levels, you will need to stop them to participate in the trial. A washout period (time without taking certain medications) is allowed if approved by your primary doctor.

What data supports the effectiveness of the treatment GLP-1A + Metformin + Mediterranean Diet for prediabetes?

Research shows that the Mediterranean diet can help prevent and manage type 2 diabetes and improve heart health, while metformin is known to help control blood sugar levels in diabetes. Combining these with GLP-1A, which is effective in managing blood sugar and weight, may offer a comprehensive approach to managing prediabetes. ^{1 2 3 4 5}

Is the combination of GLP-1 receptor agonists, Metformin, and a Mediterranean diet safe for humans?

GLP-1 receptor agonists, often used with Metformin, are generally safe for humans, with common side effects being nausea and vomiting, which usually decrease over time. They have a low risk of causing low blood sugar and are well tolerated, with some gastrointestinal issues and injection-site reactions reported. The Mediterranean diet is widely considered safe and beneficial for overall health. ^{6 7 8 9 10}

How does the treatment of GLP-1A, Metformin, and Mediterranean Diet for prediabetes differ from other treatments?

This treatment is unique because it combines a medication (GLP-1A) that helps control blood sugar, Metformin which is commonly used for diabetes, and a Mediterranean Diet known for its heart and metabolic health benefits, offering a comprehensive approach to managing prediabetes. ^{1 2 3 4 11}

What is the purpose of this trial?

The study team will invite participants with prediabetes or mild diabetes (HbA1c 5.7-7.0) to join a 5-year research study that will define subphenotypes of type 2 diabetes based on underlying physiology (eg insulin resistance, beta-cell dysfunction, incretin defect, liver insulin resistance) and then test the hypothesis that response to three first-line treatments will vary according to metabolic subphenotype. Variables of interest include glucose, cardiovascular risk markers, and weight. Treatments include Mediterranean diet, metformin, and a GLP-1 agonist. Participants will go through an initial screening, followed by three treatment periods, each lasting 4 months with 3 month washout in-between treatment periods. This study will help us understand how personalized treatments can help control blood glucose, reduce cardiovascular risk, and manage weight. While there may be minor side effects-like slight discomfort from blood tests, gastrointestinal symptoms from some of the medications, and small radiation exposure from DXA body scans-the treatments offered in this study have all been well studied and are known to lower risk for diabetes and cardiovascular disease

Research Team

Tracey L McLaughlin, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for individuals with prediabetes or mild diabetes (HbA1c levels between 5.7-7.0). It aims to identify different subtypes of type 2 diabetes and tailor treatments accordingly. Participants will undergo a series of tests and receive three first-line treatments: a Mediterranean diet, metformin, and a GLP-1 agonist over the course of five years.

Inclusion Criteria

My HbA1c level is between 5.7% and 8.0%, and I'm not taking diabetes medication.

My BMI is between 23 and 45, or between 22 and 45 if I'm Asian.

Exclusion Criteria

I do not have a history of cancer, kidney/liver disease, pregnancy, chronic inflammation, eating disorders, or bariatric surgery.

Physical activity >2 hours/day

I had a heart or blood vessel event in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants follow a Mediterranean diet for 16 weeks

16 weeks

Regular visits for monitoring and dietary guidance

Washout Period 1

Participants undergo a washout period to clear previous treatment effects

12 weeks

Treatment Period 2

Participants use a GLP-1 agonist for 16 weeks

16 weeks

Regular visits for monitoring and dose adjustments

Washout Period 2

Participants undergo a washout period to clear previous treatment effects

12 weeks

Treatment Period 3

Participants use metformin for 16 weeks

16 weeks

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• GLP-1A
• Mediterranean Diet
• Metformin

Trial Overview The study is testing how well participants with varying underlying diabetic physiology respond to three interventions: dietary changes through the Mediterranean diet, the medication metformin, and GLP-1 agonists—a type of medication that affects insulin secretion. The goal is to see which treatment works best for specific diabetic subphenotypes.

Participant Groups

Group I: Metformin/Mediterranean Diet/GLP1a Experimental Treatment 3 Interventions

1. 16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week. 2. 3 months washout 3. 16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat. 4. 3 months washout 5. 16 weeks using GLP1 agonist: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols.

Group II: Mediterranean Diet/GLP1a/Metformin Experimental Treatment 3 Interventions

1. 16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat. 2. 3 months washout 3. 16 weeks using GLP1 agonist: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols. 4. 3 months washout 5. 16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week.

Group III: GLP1a/Metformin/Mediterranean Diet Experimental Treatment 3 Interventions

1. 16 weeks using GLP1 agonist: Dosing will be titrated per clinical guidelines and as per FDA approved clinical protocols. 2. 3 months washout 3. 16 weeks of using metformin: Dosing will initiate at 500mg TID and increased to 1000mg BID after one week. 4. 3 months washout 5. 16 weeks of following a Mediterranean diet: a mostly plant-based diet that includes vegetables, whole grains, whole fruits, legumes, nuts and seeds, with fish being the primary animal protein, and olive oil the primary fat.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

GLP-1 receptor agonists (RAs) like exenatide and liraglutide have been shown to effectively lower glycated hemoglobin (A1C) levels and promote weight loss in patients with type 2 diabetes, making them beneficial treatment options alongside metformin.

These medications have a low risk of causing hypoglycemia and can improve cardiovascular risk factors, although they may cause nausea initially, which tends to decrease over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatments and strategies for type 2 diabetes: can we do better with GLP-1 receptor agonists? Peterson, G.[2018]

GLP-1 receptor analogues (GLP-1RAs) are effective treatments for type 2 diabetes, improving blood sugar control and weight management while having a low risk of hypoglycemia.

These medications work by increasing insulin secretion and reducing glucagon release in a glucose-dependent manner, and they are generally well tolerated, with gastrointestinal issues being the most common side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-Like Peptide-1 Receptor Analogues in Type 2 Diabetes: Their Use and Differential Features. Lyseng-Williamson, KA.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Mediterranean Diet and Cardiodiabesity: A Systematic Review through Evidence-Based Answers to Key Clinical Questions. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Metformin Use and Cognitive Function in Older Adults With Type 2 Diabetes Following a Mediterranean Diet Intervention. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The rationale and design of a Mediterranean diet accompanied by time restricted feeding to optimise the management of type 2 diabetes: The MedDietFast randomised controlled trial. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Mediterranean diet adherence in individuals with prediabetes and unknown diabetes: the [e-mail] Study. [2013]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Adherence to the Mediterranean diet in patients with type 2 diabetes mellitus and HbA1c level. [2022]

6. England pubmed.ncbi.nlm.nih.gov

GLP-1R agonist therapy for diabetes: benefits and potential risks. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Current treatments and strategies for type 2 diabetes: can we do better with GLP-1 receptor agonists? [2018]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Safety of Glucagon-Like Peptide-1 Receptor Agonists: A Real-World Study Based on the US FDA Adverse Event Reporting System Database. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Glucagon-Like Peptide-1 Receptor Analogues in Type 2 Diabetes: Their Use and Differential Features. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Dipeptidyl peptidase-4 (DPP-4) inhibitors are favourable to glucagon-like peptide-1 (GLP-1) agonists: no. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Adherence to a Mediterranean diet and glycaemic control in Type 2 diabetes mellitus. [2022]