Diabetes Remission Possible With Significant Weight Loss: DiRECT

Individuals with type 2 diabetes who lose a significant amount of weight through a strict dietary intervention can send their diabetes into remission, according to the results of a new study.

Nearly half of individuals who adhered to the primary care-led program for weight management no longer had type 2 diabetes at 12 months, with remission rates even higher among those who lost more weight. Among individuals who lost 15 kg or more, for example, 86% had a remission of their diabetes.

“People with type 2 diabetes can get rid of it if they’re serious enough, but they need ongoing support and buy-in from their families if they’re going to keep the weight off and keep diabetes away long-term,” senior investigator Roy Taylor, MD (Newcastle University, Newcastle-upon-Tyne, England), told TCTMD. “The important thing is that physicians can relearn about type 2 diabetes and explain to people that it’s possible for them to get out of it. They don’t need to live with this threat to their eyes, their feet, their nerves.”    

In an editorial, Matti Uusitupa, MD (University of Eastern Finland, Kuopio), calls the study findings “impressive,” saying they “strongly support the view that type 2 diabetes is tightly associated with excessive fat mass in the body.” These results, along with other studies of type 2 diabetes prevention, Uusitupa adds, “indicate that weight loss should be the primary goal” of treatment. 

Darren McGuire, MD (UT Southwestern Medical Center, Dallas, TX), who was not involved in the study, said the findings were “quite striking,” particularly the magnitude of benefit observed in the trial. Although the dietary intervention was strict, it was simple in design and embedded within usual-care practice.

“This wasn’t a complicated intervention that took a whole lot of effort above and beyond standard clinical care and a little bit of education for the investigators and patients alike,” McGuire told TCTMD. “They had some attrition and a gradient of response to the intervention, but the weight loss is remarkable—a quarter of patients lost 15 kg or more. That’s pretty remarkable in and of itself.”

The graded response—with greater remission of diabetes tied to greater weight loss—underpins the validity of the findings, added McGuire.

Too Much Fat in the Wrong Place

Speaking with TCTMD, Taylor said it has long been believed that type 2 diabetes is inevitably progressive, resulting in “patients taking more and more tablets and then eventually insulin,” with little thought the disease could be reversed. Over the last couple of decades, however, that thinking has shifted. In the bariatric surgery world, for example, there are data showing that patients who lose a significant amount of weight through surgery can achieve short- and long-term diabetes remission.

In 2011, Taylor and colleagues showed that patients with type 2 diabetes who adhered to a low-calorie diet saw their fasting plasma glucose levels return to normal within a week, even though they had stopped their antidiabetic medications. They attributed this to a change in fat levels in the liver. Over the next 8 weeks, they also observed increased insulin secretion by pancreatic beta cells. As Taylor explained, the “beta cells in the pancreas woke up, came back to life.”

Given the evidence that it was possible to reverse the course of diabetes with a low-calorie diet, the researchers launched the Diabetes Remission Clinical Trial (DiRECT) to determine if a dietary intervention could be handled by primary care practices. Taylor said the intervention “wasn’t at all clever,” just 8 hours of structured training for the clinic nurse.

In DiRECT, investigators recruited 298 individuals aged 20 to 65 years diagnosed with type 2 diabetes in the past 6 years. All participants had a body mass index ranging from 27 to 45 kg/m2m, and none were taking insulin. The intervention arm included the withdrawal of antidiabetic and antihypertensive medications and a total dietary replacement consisting of just 825-850 kcal/day for 3 to 5 months. After this, more food was introduced into the diet over a period of 2 to 8 weeks, and support was provided for long-term weight-loss maintenance. No additional exercise was prescribed to achieve the weight reduction. In the control arm, patients were treated with guideline-based, best-practice diabetes care.

In total, 23 participants were lost to follow-up by 12 months, leaving 128 individuals in the intervention arm and 147 in the control arm. Researchers obtained data on a number of these missing patients through the general practice records, however. In total, data on weight loss and diabetes remission were available for 285 and 290 participants, respectively, in the two groups.

Mean bodyweight decreased by 10 kg in the intervention arm and 1.0 kg in the control arm. In total, 24% of participants in the intervention arm met the study’s co-primary endpoint, which was a reduction in weight of 15 kg or more. In terms of diabetes remission, the study’s other primary endpoint, 46% were free of the metabolic disorder (and without medication) at 12 months in the dietary intervention group versus 4% in the control arm (P < 0.001). Mean HbA1c levels fell by 0.9% in the intervention arm and increased 0.1% in the control group (P < 0.001).

There were no reported cases of diabetes remission in patients who did not lose weight. Overall, 34% of patients who lost 5-10 kg, 57% who lost 10-15 kg, and 86% who lost 15 kg or more had a remission of diabetes. At 12 months, three-quarters of patients in the intervention arm weren’t taking antidiabetic medication compared with 18% in the control arm.

In terms of clinical practice, Taylor said physicians need to have a “frank discussion” with their diabetic patients, warning them of the long-term risks associated with the condition, and their need to lose significant weight. That means cutting what they eat in half, which will lead to a drastic reduction in weight over 3 to 6 months. “It’s restrictive, and they’ve got to make decisions every day,” he said. “It’s not for everybody.”

Taylor stressed the key to the primary care-based program is family involvement, particularly spousal support. “It’s really a team effort,” he said. “We have to look at [diabetes] from a human perspective. We’re not just fixing numbers or fat levels. We’re dealing with real people and their families.”

McGuire said the DiRECT results will surprise a lot physicians. He noted that studies with dietary interventions are often quite intensive, complete with counseling and multiple patient visits, but the present intervention is rather straightforward. This means it’s possible for physicians and nurses in clinical practice to adopt the program.

“They were able to achieve some degree of weight loss in nearly everybody,” said McGuire. 

Getting the Patient’s Attention

In the editorial, Uusitupa notes that long-term follow-up results are extremely important given that postintervention weight gain is common in weight-management studies. Additionally, the optimal time to start the prevention or treatment of type 2 diabetes with the dietary intervention is unknown. Regardless, in light of the DiRECT findings, a nonpharmacological approach should be “revived” for the treatment of obese patients with diabetes, writes Uusitupa.

McGuire said the dietary intervention could be initiated in overweight and obese patients showing signs of prediabetes or with newly diagnosed diabetes. During that visit, with abnormal laboratory values in hand, it’s an emotional moment for patients and might be the right time to intervene. 

“Historically what we’ve done is counsel patients about exercise and physical activity, rather than embark on this structured program, and we’ve had very little success, honestly,” said McGuire. “Maybe the lack of success might have been the lack of the right approach. If patients are sufficiently committed to embark on this intervention, this is the time to do it.”

To TCTMD, Taylor said the DiRECT study was initially planned as a 2-year study but recently received additional funding to follow the patients for 4 years.