Debate: Is lasting remission of type 2 diabetes feasible in the real-world setting?

The prospect of remission of type 2 diabetes (T2D) has captured the hearts and minds of many patients with T2D and health care professionals, including myself.

I have changed my narrative when supporting my patients with T2D. I used to say that T2D is a progressive condition, but considering seminal recent evidence like the DiRECT trial, I now say that T2D can be a progressive condition. Through significant weight loss, patients can reverse it and achieve remission of T2D. This has given my patients hope that their T2D is no longer an inexorable condition. And hope, of course, is a powerful enabler of change.

However, the million-dollar question is whether remission of T2D can be maintained in the long term in the real-world setting of primary care, which is chiefly where T2D is managed.

I therefore relished the opportunity to attend a debate on this topic at the annual meeting of the European Association for the Study of Diabetes in Hamburg, Germany, between Roy Taylor, MD, principal investigator for the DiRECT study and professor of medicine and metabolism at the University of Newcastle, England, and Kamlesh Khunti, MD, PhD, professor of primary care diabetes at the University of Leicester, England.

Remarkable weight loss

Dr. Taylor powerfully recapitulated the initial results of the DiRECT study. T2D remission was achieved in 46% of participants who underwent a low-energy formula diet (around 850 calories daily) for 3-5 months. After 2 years’ follow-up, an impressive 36% of participants were still in remission. Dr. Taylor then discussed unpublished 5-year extension follow-up data of the DiRECT study. Average weight loss in the remaining intervention group was 6.1 kg. I echo Taylor’s sentiment that this finding is remarkable in the context of a dietary study.

Overall, 13% of participants were still in remission, and this cohort maintained an average weight loss of 8.9 kg. Dr. Taylor concluded that lasting remission of T2D is indeed feasible in a primary care setting.

Yet he acknowledged that although remission appears feasible in the longer term, it was not necessarily easy, or indeed possible, for everyone. He used a wonderful analogy about climbing Mount Everest: It is feasible, but not everyone can or wants to climb it. And even if you try, you might not reach the top.

This analogy perfectly encapsulates the challenges I have observed when my patients have striven for T2D remission. In my opinion, intensive weight management with a low-energy formula diet is not a panacea for T2D but another tool in our toolbox to offer patients.

He also described some “jaw-dropping” results regarding incidence of cancer: There were no cases of cancer in the intervention group during the 5-year period, but there were eight cases of cancer in the control group. The latter figure is consistent with published data for cancer incidence in patients with T2D and the body mass index (BMI) inclusion criteria for the DiRECT study (a BMI of 27-45 kg/m²). Obesity is an established risk factor for 13 types of cancer, and excess body fat entails an approximately 17% increased risk for cancer-specific mortality. This indeed is a powerful motivator to facilitate meaningful lifestyle change.

In primary care, we also need to be aware that most weight regain usually occurs secondary to a life event (for example, financial, family, or illness). We should reiterate to our patients that weight regain is not a failure; it is just part of life. Once the life event has passed, rapid weight loss can be attempted again. In the “rescue plans” that were integral to the DiRECT study, participants were offered further periods of total diet replacement, depending on quantity of weight gain. In fact, 50% of participants in DiRECT required rescue therapy, and their outcomes, reassuringly, were the same as the other 50%.

Dr. Taylor also quoted data from the ReTUNE study suggesting that weight regain was less of an issue for those with initial BMI of 21-27, and there is “more bang for your buck” in approaching remission of T2D in patients with lower BMI. The fact that people with normal or near-normal BMI can also reverse their T2D was also a game changer for my clinical practice; the concept of an individual or personal fat threshold that results in T2D offers a pragmatic explanation to patients with T2D who are frustrated by the lack of improvements in cardiometabolic parameters despite significant weight loss.

Finally, Dr. Taylor acknowledged the breadth of the definition of T2D remission: A1c < 48 mmol/mol at least 2 months off all antidiabetic medication. This definition includes A1c values within the “prediabetes” range: 42-47 mmol/mol.

He cited 10-year cardiovascular risk data driven by hypertension and dyslipidemia before significant weight loss and compared it with 10-year cardiovascular risk data after significant weight loss. Cardiovascular risk profile was more favorable after weight loss, compared with controls with prediabetes without weight loss, even though some of the intervention group who lost significant weight still had an A1c of 42-47 mmol/mol. Dr. Taylor suggested that we not label these individuals who have lost significant weight as having prediabetes. Instead “postdiabetes” should be preferred, because these patients had more favorable cardiovascular profiles.

This is a very important take-home message for primary care: prediabetes is more than just dysglycemia.