Very Low Calorie Diet for Obesity and Type 2 Diabetes

Recruiting in Greenville (>99 mi)

Overseen By Sandra Garcia Juarez, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Durham VA Medical Center

Must be taking: GLP-1 agonist

Must not be taking: Immunosuppressants, Anticoagulants, Prednisone

Disqualifiers: Pancreatitis, Gastroparesis, Thyroid cancer, 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: 4

Duration: 50 weeks

50 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop your current medications. However, you must be on a stable dose of a once-weekly GLP-1 agonist and can be on other diabetes medications. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Medically Reproduced Bariatric Surgery (MRB) for obesity and type 2 diabetes?

Research shows that a very low-calorie diet can help people with obesity and type 2 diabetes lose weight and improve their blood sugar control. This suggests that similar treatments, like Medically Reproduced Bariatric Surgery, might also be effective. ^{1 2 3 4 5}

Is a very low calorie diet safe for humans?

Research shows that very low calorie diets (VLCDs) have been used safely in humans, including for people with obesity and type 2 diabetes. These diets have been studied for their effects on weight loss, diabetes management, and surgery preparation, with no major safety concerns reported in the studies. ^{3 5 6 7 8}

How is the Medically Reproduced Bariatric Surgery (MRB) treatment different from other treatments for obesity and type 2 diabetes?

The Medically Reproduced Bariatric Surgery (MRB) treatment is unique because it mimics the effects of bariatric surgery through a very low-calorie diet, which can improve blood sugar control and reduce insulin needs in patients with type 2 diabetes, potentially leading to diabetes remission without actual surgery. ^{1 2 3 9 10}

What is the purpose of this trial?

Roux-en-Y (RYGB) gastric bypass reduces the size and capacity of the stomach and bypasses a portion of the small intestine which leads to decreased food intake and higher levels of a gut hormone called GLP-1 (glucagon-like-peptide-1). These changes lead to weight loss, improved blood sugars and often remission of type 2 diabetes but most patients do not qualify or want surgery. The investigators are searching for ways to make the beneficial effects of RYGB available to most type 2 diabetes patients rather than a select few that undergo RYGB. The investigators believe that parts of RYGB can be medically reproduced through a combination of diet and medicine. Once weekly injectable GLP-1 medicine that leads to weight loss and improved blood sugar control in type 2 diabetes are now FDA approved. Optifast is a medically supervised diet that safely reduces calorie intake to 800 calories per day for three months by replacing normal meals with specially prepared bars and shakes which leads to weight loss and improved blood sugar control in type 2 diabetes. Normal meals are then gradually reintroduced over 6 weeks and the bars/shakes are stopped. The investigators hypothesize that Optifast (diet) + once weekly GLP-1 will lead to weight loss and improvement in blood sugar control in type 2 diabetes similar to what is seen after RYGB.

Research Team

Moahad Dar, MD

Principal Investigator

Department of Veteran Affairs

Eligibility Criteria

This trial is for individuals with obesity and type 2 diabetes who are looking for an alternative to bariatric surgery. Participants should be interested in a medically supervised diet combined with medication that mimics the effects of gastric bypass surgery.

Inclusion Criteria

I am between 25 and 75 years old.

Using a Freestyle Libre glucose monitoring device and/or glucometer device

BMI >27

Exclusion Criteria

Any serious and/or unstable medical, psychiatric, or other condition(s) that prevents the patient from providing informed consent or complying with the study

Unstable psychiatric condition including active or current suicidal ideation

I am over 75 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Participants in the experimental arm undergo a 2-week run-in phase to determine tolerance to Isocaloric Optifast

2 weeks

Weekly meetings

Treatment

Participants receive Optifast + once weekly GLP-1 agonist with medical drug management and nutritional/behavioral counseling

50 weeks

4 in-person visits at baseline, week 12, week 24, and week 48

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Medically Reproduced Bariatric Surgery (MRB)

Trial Overview The study tests if a very low calorie diet (Optifast) along with a weekly injectable GLP-1 medicine can replicate the weight loss and blood sugar control benefits typically seen after Roux-en-Y gastric bypass surgery in patients with type 2 diabetes.

Participant Groups

Group I: Very Low Calorie Diet Experimental Treatment 1 Intervention

Patients in the experimental group will attend 4 in-person visits with the study coordinator at baseline, week 12, week 24, and week 48 to measure study outcomes. Additionally, they will undergo a 2 week run-in phase before baseline with weekly meetings to ensure that they are able to tolerate and comply with Optifast. Patients will get medical drug management (endocrinologist), nutritional/behavioral counseling (dietician, psychologist) and will be maintained on Optifast + once weekly GLP-1 agonist +/- other diabetic medicines.

Group II: Standard of Care Active Control 1 Intervention

Patients in the control group will attend four in-person visits with the study coordinator at baseline, week 12, week 24, and week 48 to measure study outcomes. Patients will get medical drug management (endocrinologist), nutritional/behavioral counseling (dietician, psychologist) and will be maintained on once weekly GLP-1 agonist +/- other diabetic medicines.

Who Is Running the Clinical Trial?

Durham VA Medical Center

Lead Sponsor

Trials

40

Recruited

9,300+

Société des Produits Nestlé (SPN)

Industry Sponsor

Trials

349

Recruited

63,400+

Findings from Research

In a study of 27 obese patients with type 2 diabetes, adding exercise to a very low-calorie diet (VLCD) resulted in greater fat loss and increased skeletal muscle mitochondrial DNA content compared to the VLCD alone.

While both groups showed similar improvements in insulin-stimulated glucose disposal, only the exercise group experienced significant enhancements in maximum aerobic capacity, indicating that exercise provides additional benefits beyond weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of adding exercise to a 16-week very low-calorie diet in obese, insulin-dependent type 2 diabetes mellitus patients. Snel, M., Gastaldelli, A., Ouwens, DM., et al.[2012]

A very-low-calorie diet (VLCD) of 600 kcal/day was effective in inducing short-term remission of type 2 diabetes in 79% of the 19 Thai patients studied, with significant improvements in glycemic control and beta cell function observed within the first 2 weeks.

After 12 months, about 30% of participants maintained diabetes remission without medication, indicating that while VLCD can provide rapid benefits, long-term maintenance of glycemic control may require additional strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immediate and long-term effects of a very-low-calorie diet on diabetes remission and glycemic control in obese Thai patients with type 2 diabetes mellitus. Umphonsathien, M., Prutanopajai, P., Aiam-O-Ran, J., et al.[2023]

Very low energy diets (VLEDs) are effective for significant weight loss in overweight or obese adults with Type 2 diabetes, showing greater weight loss compared to standard care and minimal interventions over 3 and 6 months, based on a meta-analysis of 9 studies with 346 participants.

Adherence to VLEDs appears to be high, with no significant differences in attrition rates compared to other interventions, although the support provided to participants during the diet was often not well documented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and acceptability of very low energy diets in overweight and obese people with Type 2 diabetes mellitus: a systematic review with meta-analyses. Rehackova, L., Arnott, B., Araujo-Soares, V., et al.[2022]

A very-low-calorie diet (VLCD) was effective in promoting significant weight loss and improving lipid profiles in 28 extremely obese subjects over one month, indicating its potential as a safe treatment for obesity.

The VLCD also led to a decrease in hyperinsulinism, which, while not statistically significant, suggests metabolic benefits that could reduce the risk of atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of extreme obesity with a very low calorie diet]. Ivković-Lazar, T.[2009]

In a study of 325 participants who underwent a very low calorie diet (VLCD) program 15 years ago, long-term weight loss maintenance was rare, with only 5.9% managing to keep off more than 10% of their initial body weight.

The study found that while some participants experienced remission of type 2 diabetes shortly after the VLCD, lasting remission was uncommon, and 21.4% developed new glucose intolerance, indicating that the VLCD may not effectively prevent diabetes in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body weight, diabetes incidence vascular events and survival 15 years after very low calorie diet in community medical clinics in the UK. Paisey, R., Daniels, C., Howitt, W., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of adding exercise to a 16-week very low-calorie diet in obese, insulin-dependent type 2 diabetes mellitus patients. [2012]

2. United States pubmed.ncbi.nlm.nih.gov

Diabetes remission and glycemic response to pre-bariatric surgery diet. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Immediate and long-term effects of a very-low-calorie diet on diabetes remission and glycemic control in obese Thai patients with type 2 diabetes mellitus. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and acceptability of very low energy diets in overweight and obese people with Type 2 diabetes mellitus: a systematic review with meta-analyses. [2022]

5. Serbia pubmed.ncbi.nlm.nih.gov

[Treatment of extreme obesity with a very low calorie diet]. [2009]

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

Body weight, diabetes incidence vascular events and survival 15 years after very low calorie diet in community medical clinics in the UK. [2022]

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

The effect of a very low calorie diet on insulin sensitivity, beta cell function, insulin clearance, incretin hormone secretion, androgen levels and body composition in obese young women. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Effectiveness and Tolerability of a Two-Week Hypocaloric Protein-Rich Diet Prior to Obesity Surgery with Two Different Diet Interventions: a Prospective Randomized Trial. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of a Very Low-Calorie Ketogenic Diet on Weight Regain Following Bariatric Surgery. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. [2022]