Lifestyle Interventions or Medication for Type 2 Diabetes?

Nadine Eckert

June 27, 2022

Lifestyle modifications are still the foundation of therapy for patients with type 2 diabetes, but in everyday practice, they are rarely successful. At the same time, highly effective medicinal therapy options are available. Should healthcare professionals simply stop advising people to eat less and become more active and instead prescribe one of the ever more potent medications? Expert opinion is broadly divided on this subject, as the Diabetes Congress in Berlin, Germany, showed.

Diets Promote Remission

Stephan Martin, MD, of the West German Diabetes and Health Center in Düsseldorf, Germany, is convinced that lifestyle modification is indispensable for type 2 diabetes therapy. "It is the opportunity to overcome type 2 diabetes simply through a change to your daily habits."

Low-calorie meal replacements have proven to be particularly effective. The effect of these liquid meals was investigated in the Diabetes Remission Trial (DiRECT) in an overall population of 306 overweight and obese diabetes patients. Of these patients, 24% achieved a weight loss of more than 15 kg, and for 46%, the patients' diabetes went into clinical remission. Clinical remission was defined as an A1c value less than 6.5% after 12 months without taking antidiabetic medication.

"On average, the patients had had type 2 diabetes for 4 years and had been taking sometimes two or three medications before the study. These medications could all be discontinued because the HbA1c value was under 6.5%," said Martin.

New Diagnoses, Good Prognosis

Of the patients who lost at least 15 kg in the study, 86% went on to achieve remission. "This means that if someone is newly diagnosed with diabetes, they probably have an almost 100% chance of reaching remission, and with clear weight loss, too," said Martin.

Among patients with type 2 diabetes, postprandial insulin production is reduced. But the DiRECT study suggested that if patients lose weight, normal postprandial insulin secretion can be achieved within 8 weeks.

Waking Up Beta Cells

"For type 2 diabetes, this depends on whether the beta cells are broken or if they're in a state of hibernation," said Martin. During "hibernation," the beta cells are displaced because the liver has reached its capacity for fat storage and fat is now being deposited in the pancreas, according to the hypothesis of the DiRECT study group.

"A radical change in diet leads to the liver losing that fat, even if nothing else is happening with the subcutaneous fatty tissue, for example," Martin explained. The working group assumes that if fat is lost from the liver, then fat is also lost from the pancreas.

Individual Fat Threshold

"For a long time, it was thought that to tackle type 2 diabetes, you had to lose a lot of weight," said Martin. "But that is clearly not the case. Even massively overweight patients just need to fall below their individual fat threshold."

With 306 participants, the DiRECT study was quite small. However, other studies have confirmed the results. In the DIADEM-1 study, which was performed by Katar with 147 patients, 61% achieved clinical remission. A comparable study in Canada, which was conducted in pharmacies, used low-calorie meal replacement with reduced carbohydrate content. With this diet, 35% of all participants were able to discontinue their diabetes medication after 1 year.

Patients Become Treatable Again

The TeLiPro study, which was conducted in Germany, included telemedical coaching in addition to a low-calorie liquid diet with reduced carbohydrate content. The 200 patients in the study had had type 2 diabetes for 11 years on average. The intervention was associated with positive effects on A1c, weight, blood pressure, body mass index, hunger, and insulin requirement. "Patients become treatable again, even if they have had diabetes for many years," said Martin.

There is no truly good predictor of which patients will respond to an extremely low-calorie liquid diet and achieve remission. "This means that we have to offer it to patients to see whether it works, and the majority manage it," said Martin. "These patients continue to have type 2 diabetes; they are not healed, and they still have to push on. They are not taken out of the disease management program."

Type 2 diabetes doesn't have to be a one-way street, said Martin. "There is a way back to being healthy. But for this to happen, we also have to demand something of our patients." The low-calorie meal replacement is suited for this, since it can lead to quick and visible success, which in turn strengthens the patients' motivation.

Cardiovascular–Renal Disease

Stephan Jacob, MD, a diabetologist at the Prevention and Therapy Practice at the Cardiometabolic Institute in Villingen-Schwellingen, has a much more pessimistic outlook on the potential of lifestyle intervention. "Type 2 diabetes is more than hyperglycemia. It is a cardiovascular–renal disease that begins long before the first diagnosis of an abnormally high blood sugar."

Studies show that atherosclerotic changes develop mostly at a time when the blood sugar is not abnormally high. "Forty percent of patients have already developed some microvascular changes by the point of diagnosis," said Jacob. "And more than 80% of type 2 diabetics have a metabolic syndrome."

Preventing Cardiovascular Events

People with type 2 diabetes are "absolute risk patients who do not live longer because of a blood sugar correction," said Jacob. Improving a factor such as blood pressure or blood sugar is only of benefit if cardiovascular and renal events are prevented as a result and survival is prolonged.

The evidence that lifestyle modification can do this is extremely limited. In the Diabetes Prevention Program (DPP) study, beneficial effects on A1c, blood pressure, and weight were seen after 18 years, but there was no effect on cardiovascular effects or on mortality.

Thirty-year data from the Da Qing Diabetes Prevention Outcome Study show a reduction in severe cardiovascular events and reduced mortality in the lifestyle group. "But first you have to actually live that long to have the benefit," commented Jacob.

Even the study with the greatest expectations, the LookAHEAD study, failed to demonstrate any improvement in severe cardiovascular endpoints following intensive lifestyle intervention.

Pharmacotherapy's Clear Successes

In stark contrast to this are the success stories from pharmacotherapy. "For patients with type 2 diabetes, SGLT2 inhibitors and GLP-1 receptor agonists have been successful in preventing serious cardiovascular events, even in primary prevention," said Jacob.

"In light of the clear data for medicinal intervention, we must not withhold evidence-based therapy from our patients." The times in which patients are first advised to go on a diet are in the past.

However, it might not be possible to get this kind of clear data for lifestyle interventions, Martin explained. "For many, there is simply not the required evidence, that's true. But we will also never get this evidence." He added, "The criteria for evidence-based medicine that is used in pharmacological studies cannot be transferred to studies on lifestyle."

Analyzing "Soft Parameters"

Martin also questioned why "only heart attack prevention and survival prolongation" matter. He recommended that much more significance be attributed to "soft parameters." "If I help a patient to lose weight through a lifestyle intervention, I give them the opportunity to move more again, maybe avoid a knee operation. That is then much more important for the patient than living for an extra 2 years after 30 years."

This article was translated from the Medscape German edition.

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