Diet Modification for Type 2 Diabetes

(LEGEND Trial)

No longer recruiting at 1 trial location

Overseen By Rick Hecht, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Must not be taking: Weight loss medications, Systemic steroids

Disqualifiers: Pregnancy, Bariatric surgery, Vegan, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two different diets to help individuals with type 2 diabetes manage blood sugar and body weight. Participants will follow either a very low-carbohydrate diet (also known as a ketogenic or low-carb diet) or a moderate-carbohydrate plate-method diet for one year to determine which is more effective. It suits those with type 2 diabetes who are not currently on a strict diet and are open to trying one of these eating plans. The trial includes regular visits and check-ins to monitor progress. As an unphased trial, it provides a unique opportunity to explore new dietary strategies for managing diabetes.

Will I have to stop taking my current medications?

If you are taking an SGLT2 inhibitor medication, you will need to stop it if you are assigned to the very low-carbohydrate diet. The protocol does not specify about other medications.

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

A previous study found very low-carbohydrate diets generally safe for people with type 2 diabetes. These diets improved insulin use within two weeks. However, other research shows that while these diets can lower blood sugar levels, they offer no significant advantage over other diets.

Research on the moderate-carbohydrate plate-method diet also suggests safety. Participants experienced a decrease in HbA1c, a measure of blood sugar levels, over time, indicating positive diabetes management. No significant harm was reported with this diet.

Both dietary approaches appear well-tolerated, with no major safety concerns reported in the studies mentioned. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these diets for type 2 diabetes because they offer new ways to manage blood sugar levels without relying solely on medication. Unlike typical treatments that often involve drugs like metformin or insulin, these diets focus on changing carbohydrate intake. The very low-carbohydrate diet aims to significantly reduce carbs, potentially leading to better control of blood sugar spikes. Meanwhile, the moderate-carbohydrate plate-method diet emphasizes balanced meals with controlled portions, which can be easier to maintain long-term. These dietary approaches could provide more personalized and sustainable options for managing diabetes.

What evidence suggests that this trial's dietary approaches could be effective for type 2 diabetes?

In this trial, participants will follow one of two diet plans. Research has shown that a very low-carbohydrate diet, one of the study arms, can help people with type 2 diabetes by lowering blood sugar levels and triglycerides (a type of fat in the blood). One study found that insulin sensitivity improved by 75%, and blood sugar levels (measured by HbA1c) dropped from 7.3% to 6.8% in just two weeks. Meanwhile, the moderate-carbohydrate plate-method diet, another arm of this trial, has also shown promise. Participants on this diet saw their HbA1c decrease by 0.7% in the first three months, with further reductions at six months. Both diets have potential for improving blood sugar control, but their long-term benefits are still under investigation. ^{2 6 7 8 9}

Who Is on the Research Team?

Laura Saslow, PhD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for English-speaking adults with type 2 diabetes, who have an HbA1c level between 6.5% and <12%, can do light exercise, and are willing to follow a new diet plan for a year. Pregnant women, those over 400 pounds, or on certain diets or medications are excluded.

Inclusion Criteria

I am willing to follow any diet assigned to me in the study.

I have type 2 diabetes with an HbA1c level between 6.5% and 12%.

I have type 2 diabetes with an HbA1c level between 6.5% and 12%.

Exclusion Criteria

I have had kidney stones multiple times or recently.

I am willing and able to attend study sessions and classes.

I am currently in a weight loss program or plan to join one soon.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow either a very low-carbohydrate or a plate-method diet for 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Moderate-carbohydrate plate-method diet
• Very low-carbohydrate diet

Trial Overview The study compares two diets: a moderate-carbohydrate plate-method diet versus a very low-carbohydrate diet to see which one better improves blood sugar control and body weight in type 2 diabetes patients over the course of one year.

How Is the Trial Designed?

Group I: Very low-carbohydrate diet Experimental Treatment 1 Intervention

Group II: Moderate-carbohydrate plate-method diet Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study involving 89 participants with type 2 diabetes, a very low-calorie ketogenic (VLCK) diet led to significantly greater weight loss and improved glycemic control compared to a standard low-calorie diet over 4 months.

The VLCK diet was found to be safe and well-tolerated, with no serious adverse events reported and no significant changes in laboratory safety parameters, indicating it can be a viable option for managing obesity in T2DM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Goday, A., Bellido, D., Sajoux, I., et al.[2022]

Low-carbohydrate diets have shown positive results in treating diabetes, pre-diabetes, metabolic syndrome, and obesity, with evidence from randomized trials and meta-analyses indicating they are safe and effective for improving health outcomes in diabetic patients.

These diets can lead to significant benefits such as weight loss, reduced medication needs, and even remission in some cases of type 2 diabetes, although they are not yet widely recognized in Czech diabetology due to ongoing safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate diet in diabetes mellitus treatment. Krejčí, H., Vyjídák, J., Kohutiar, M.[2019]

A 21-day very low-calorie ketogenic diet (VLCKD) resulted in significant weight loss and improvements in insulin resistance without negatively impacting overall nutritional status or causing adverse changes in liver and kidney function.

Both VLCKD1 and VLCKD2 led to similar reductions in body mass index and fat mass, but also resulted in increased levels of uric acid and creatinine, indicating the need for monitoring these parameters during such diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of very-low-calorie ketogenic diet: a double blind randomized crossover study. Colica, C., Merra, G., Gasbarrini, A., et al.[2022]

The modified Atkins diet, a less restrictive version of the ketogenic diet, has shown good efficacy and tolerability in treating refractory epilepsy, making it a promising dietary intervention.

This diet can be initiated on an outpatient basis without fasting, allowing unlimited protein and fat intake, which may improve adherence compared to more restrictive diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The modified atkins diet in refractory epilepsy. Sharma, S., Jain, P.[2022]

A 42-year-old woman with type 2 diabetes experienced euglycemic diabetic ketoacidosis (euDKA) after starting a sodium-glucose co-transporter 2 (SGLT2) inhibitor while on a very low carbohydrate ketogenic diet (VLCKD), highlighting the risk of this combination.

After recovering from euDKA and stopping the SGLT2 inhibitor, she successfully resumed a VLCKD under medical supervision and maintained ketosis safely for 2 years, demonstrating that with proper monitoring, VLCKD can be safely reimplemented post-euDKA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SUCCESSFUL REIMPLEMENTATION OF A VERY LOW CARBOHYDRATE KETOGENIC DIET AFTER SGLT2 INHIBITOR ASSOCIATED EUGLYCEMIC DIABETIC KETOACIDOSIS. Fieger, EI., Fadel, KM., Modarres, AH., et al.[2022]

In a 16-week study involving 28 overweight participants with type 2 diabetes, the low-carbohydrate, ketogenic diet (LCKD) led to a significant 16% reduction in hemoglobin A1c levels, indicating improved glycemic control.

The diet also allowed for the discontinuation or reduction of diabetes medications in 17 out of 21 participants who completed the study, highlighting the need for close medical supervision when implementing such dietary changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Yancy, WS., Foy, M., Chalecki, AM., et al.[2020]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1751991822000687

Effectiveness of restricted diet with a plate in patients ... Participants in the plate model reduced HbA1c by 0.7% in the first three months, and reduced to a greater extent at six months (1.44%), but this was not ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9609579/

Comparison of the Effectiveness of Low Carbohydrate ... LC diet significantly reduced body weight, BMI, fasting insulin and triglycerides and increased total cholesterol and HDL-C levels at the short-to-intermediate ...

3. nature.com nature.com/articles/s41387-017-0006-9

Twelve-month outcomes of a randomized trial ... In a 12-month trial, adults with elevated HbA1c and body weight assigned to an LCK diet had greater reductions in HbA1c, lost more weight, and reduced more ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05237128?intr=LEGEND&aggFilters=studyType:int&viewType=Table&rank=1

The Lifestyle Education About Nutrition for Diabetes ... This research will test whether a very low-carbohydrate or a plate-method diet better improves outcomes for blood glucose control and body composition for ...

5. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07512-9

Protocol for a randomized controlled trial comparing a very ... Some evidence indicates that reducing overall carbohydrate intake with a low- or very low-carbohydrate eating plan can improve glycemic control ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10360267/

Protocol for a randomized controlled trial comparing a very ... The LEGEND trial is a randomized controlled trial to assess optimal carbohydrate intake in type 2 diabetes by evaluating the effects of a very low-carbohydrate ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6767093/

Improving the scientific rigour of nutritional recommendations ... Of the 10 studies that reported on lipids, five found significant improvements in triglycerides with a low‐carbohydrate diet74, 78, 82, 83, 84; none resulted ...

8. bmj.com bmj.com/content/372/bmj.m4743

Efficacy and safety of low and very low carbohydrate diets ... Moderate to low certainty evidence suggests that patients adhering to LCDs for six months may experience greater rates of remission of diabetes ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0002916522000090

Dose-dependent effect of carbohydrate restriction for type 2 ... Levels of most cardiometabolic outcomes decreased linearly with the decrease in carbohydrate intake. U-shaped effects were seen for total cholesterol and LDL ...