Very Low Calorie Diet for Obesity and Type 2 Diabetes

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a very low-calorie diet combined with a weekly injection can mimic the effects of gastric bypass surgery for people with type 2 diabetes. By replacing regular meals with special bars and shakes, the study aims to achieve significant weight loss and improve blood sugar levels, similar to the benefits of surgery, but without the need for surgery itself. The trial includes two groups: one trying the new diet and medicine combination, known as Medically Reproduced Bariatric Surgery (MRB), and the other receiving standard care. It seeks participants with type 2 diabetes, a BMI over 27, and those already using a weekly injection to manage their diabetes. As a Phase 2, Phase 3 trial, this study measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to benefit from cutting-edge research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that very low-calorie diets (VLCDs) can help people with type 2 diabetes lose significant weight and better control their blood sugar. Studies have found that these diets not only aid in weight loss but also improve blood sugar levels. Many patients also require less diabetes medication. The American Diabetes Association supports using VLCDs for up to three months, provided a healthcare provider supervises.

The FDA has already approved GLP-1 medication for aiding weight loss and blood sugar control in type 2 diabetes, indicating it has been tested and found safe and effective for individuals with this condition.

Together, these treatments offer a safe way to manage weight and blood sugar, providing benefits similar to those of gastric bypass surgery, but without the need for surgery. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Medically Reproduced Bariatric Surgery (MRB) treatment because it offers a novel approach to managing obesity and Type 2 diabetes. Unlike the standard care, which typically involves lifestyle changes and medications like GLP-1 agonists, MRB mimics the effects of bariatric surgery through a very low-calorie diet using Optifast, combined with medical and nutritional support. This method aims to deliver the benefits of surgery without the need for invasive procedures, potentially offering significant weight loss and improved blood sugar control. Additionally, the inclusion of a GLP-1 agonist may enhance the treatment's effectiveness in managing diabetes, making it a promising option for those struggling with these conditions.

What evidence suggests that this trial's treatments could be effective for obesity and type 2 diabetes?

In this trial, participants in the experimental group will follow a very low-calorie diet (VLCD) using Optifast. Research shows that this approach can help individuals with obesity and type 2 diabetes lose significant weight and improve blood sugar levels. Studies have found that these diets can result in a 13-18% weight loss by reducing daily calorie intake to less than 800 calories. Evidence also suggests that VLCDs can sometimes lead to diabetes remission.

Participants in this group will also receive GLP-1 medications, taken once a week, which the FDA has approved for aiding weight loss and blood sugar control. The trial will assess whether combining the Optifast diet with GLP-1 medication offers benefits similar to gastric bypass surgery, without requiring surgery. This combined approach could lead to outcomes similar to those seen in patients who have undergone Roux-en-Y gastric bypass, including weight loss and improved diabetes management. ^{4 6 7 8 9}

Who Is on the Research Team?

Moahad Dar, MD

Principal Investigator

Department of Veteran Affairs

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6587830/

Effectiveness of a Total Meal Replacement Program ... At 52 weeks, percent weight loss was 10.5% ± 0.6% for OP versus 5.5% ± 0.6% for FB (difference 4.9% ± 0.9%; P < 0.001) (Figure 2). Sensitivity analyses showed ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0261561424002267

Metabolic effects of very-low calorie diet, Semaglutide, or ... By limiting daily energy intake to less than 800 kilocalories (kcal), VLCD interventions result in approximately 13–18% weight loss [7,8]. Furthermore, in the ...

3. bjd-abcd.com bjd-abcd.com/index.php/bjd/article/view/793/1051

View of Very low-calorie diet in patients with longstanding ... Results: There was a significant reduction in weight of 9.96 kg (p<0.001) immediately post-VLCD, with net weight loss sustained to 12 months (p<0.05). There was ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39118237

Very-low-calorie diet-based intensive lifestyle intervention ... Very low-calorie diet (VLCD) can induce weight loss and diabetes remission (DR) amongst people with obesity and recent-onset type 2 diabetes (T2D).

5. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.15819

The latest evidence and clinical guidelines for use of meal ... The historical development, efficacy and safety of very-low-calorie diets ... Using a low-carbohydrate diet to treat obesity and type 2 diabetes ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26435354/

A Systematic Review of Evidence on the Use of Very Low ... This review demonstrated that VLCD in people with T2D was associated with significant weight loss, reduction in blood glucose profile and improvement in ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5368342/

Weight losses with low-energy formula diets in obese ... Weight losses with liquid-formula diets are very similar for VLCD and LELD and for obese subjects with or without T2DM.

8. tandfonline.com tandfonline.com/doi/full/10.1080/16070658.2016.1216514

The Use of Very Low Calorie Diets in the Management ... The latest guidelines from the American Diabetes Association suggest that VLCDs (≤800 kcal) can be used for 3 months provided that the treating ...

9. bmj.com bmj.com/content/372/bmj.m4743

Efficacy and safety of low and very low carbohydrate diets ... Diets with very low carbohydrates (<10% of daily calories from carbohydrates) led to smaller weight loss at six months (mean difference –1.05, – ...