Semaglutide and very low-calorie diet may be best for type 2 diabetes control

• Combining a popular drug used for weight loss and as a diabetes treatment, combined with a form of calorie restriction may be a particularly effective way to manage type 2 diabetes.
• The combination treatment appeared to improve the functioning of cells that produce insulin.
• Although encouraging, these results are preliminary and need replicating.

A recent study published in Clinical Nutrition concludes that combining semaglutide ( Ozempic ) with a very low-calorie diet may be a more effective way to treat type 2 diabetes than either approaches in isolation.

They found that a very low-calorie diet produced greater short-term weight loss than semaglutide. Also, adding a very low-calorie diet to the treatment with semaglutide produced more weight loss than semaglutide alone.

However, the combination treatment did not produce greater weight loss than a very low-calorie diet alone.

Importantly, the a very low-calorie diet and semaglutide in unison did produce greater improvements in pancreatic beta cell function — the cells of the pancreas that produce insulin.

What role do beta cells play in diabetes?

Type 2 diabetes is a signficant and growing concern in the United States and further afield. The swift increase in prevalence has sparked a surge of research in recent years.

It is now clear that increased levels of body fat increase the risk of developing the condition. Obesity is linked with a sevenfold increase in risk.

The link between obesity and type 2 diabetes is at least partly because excess weight is linked to insulin resistance and reduced functioning of beta cells .

This is a double-edged sword: Insulin resistance means that the body’s tissues no longer respond properly to insulin, while dysfunctional beta cells mean that the pancreas produces less insulin.

In other words, obesity means that less insulin is available, and the insulin that is available no longer works as effectively.

What is the best approach to diabetes treatment?

Because excess weight plays such a significant role in type 2 diabetes risk, weight loss is an important part of diabetes management.

Semgalutide was originally designed to treat type 2 diabetes. It works by increasing the amount of insulin produced after eating, which helps keep blood sugar within healthy limits.

It also suppresses the production of glucagon, a hormone that increases blood sugar levels and may improve beta cell function. More recently, semaglutide has risen to fame as a powerful weight-loss medication.

Similarly, studies have shown that following a very low-calorie diet — 800 calories per day — can produce significant weight loss .

Studies also show that a very low-calorie diet can improve blood sugar control and even reverse type 2 diabetes. These improvements may be due to improved beta cell function .

Very low-calorie diets, however, are incredibly difficult to stick to. In some studies, one-third of participants following a very low-calorie diet dropped out, unable to maintain the low energy intake.

Although the evidence for both interventions is good, there are no direct comparisons between the two approaches. Also, no studies have investigated how effective a very low-calorie diet and semaglutide might be in combination. The new study addresses this void.

Semaglutide vs low-calorie diet for diabetes

To investigate, the scientists recruited 30 participants with type 2 diabetes. They were randomly assigned into three groups:

1. semaglutide
2. very low-calorie diet — 800 calories per day
3. semaglutide plus very low-calorie diet .

The study ran for 12 weeks. Before and at the end of the study, the scientists assessed:

• body weight.
• glycated haemoglobin (HbA1c) — a measure of blood sugar levels.
• dual energy X-ray absorptiometry — a method of measuring body composition.
• intravenous glucose tolerance tests (IVGTT) — this assesses the first phase of insulin release and is a marker of beta cell function.

“Insulin is secreted in a biphasic manner — two waves, so to speak — from the pancreas. The first phase is the initial secretion of insulin in response to sugar in the system,” Mir Ali, MD , told Medical News Today .

Ali is a board-certified bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA. He was not involved in the study.

While the first phase is rapid and triggered by glucose in the blood, the later, second phase is longer and slower and not dependant on blood sugar.

Semaglutide plus low-cal diet best for diabetes control

At the end of the study, the scientists found that a very low-calorie diet and the combination of a very low-calorie diet and semaglutide led to significantly greater reductions in body weight and fat mass than semaglutide alone.

Both HbA1c and fasting glucose reduced significantly in all three groups. Importantly, fasting insulin levels and insulin sensitivity only improved in the very low-calorie diet group and combination group.

The scientists also found that the insulin first phase response increased in those taking semaglutide alone and those in the combination group. This increase was more pronounced in the combined treatment than the very low-calorie diet.

In short, following a very low-calorie diet induced more weight loss than semaglutide, but the combination of both worked best. The combination also drove greater improvements in the function of beta cells — an important marker of better diabetes control.

Franklin Joseph, MD , Chief Medical Officer at Dr. Frank’s Weight Loss Clinic, who was not involved in this study, spoke with MNT about the results. He was surprised that “although the [very low-calorie diet] resulted in greater reductions in weight, fat mass, and insulin resistance, it did not appear to enhance beta cell function.”

The authors suggest that this is because the participants had been living with type 2 diabetes for a long time. According to Joesph, this underlines the fact that “aggressive weight loss interventions to try and achieve remission need to happen early in the diabetes journey.”

Is this approach viable in the long term?

This study suggests that a combination of following a very low-calorie diet and semaglutide might be an effective way to help manage type 2 diabetes. However, this was just a pilot study with a small group of participants, so much more work is needed.

Also, 12 weeks is a relatively short time frame to assess weight loss and type 2 diabetes management. Understanding what happens in the long run is important.

Speaking with MNT , ​ Megan Warnke, RDN , a registered dietician nutritionist and Certified Diabetes Care and Education Specialist, also not involved in this research, explained that a very low-calorie diet is not viable approach beyond a short-term intervention:

“The key words in this study are ‘short term results.’ Like with any diet, this approach may work for a short period of time, but it’s not sustainable for long term results.”

Also, “appetite suppression from semaglutide can help patients follow a calorie-restricted diet, but other factors like stress, sleep, and food insecurity will also impact diet ‘success,’ which is something this drug can’t fix,” Warnke explained.

In agreement, Joseph told MNT , that “[t]he use of semaglutide for its appetite control effect would be a great adjunct in allowing people to embark upon and sustain a [very low-calorie diet].”

But many questions remain. “Will the appetite come back with a vengeance due to rebound hunger and result in rapid weight regain?” posited Joseph. “Would the completion of the [very low-calorie diet] for a fixed duration and continuation of the semaglutide longer-term help to maintain the weight loss and glycemic control achieved?”

Overall, Joseph believes this approach may, in the future, be useful. “More and more, our focus has been on trying to achieve diabetes remission in patients as early as possible and improvements in beta cell function would suggest that this approach would possibly be more beneficial in achieving remission,” he noted.