Weight loss of 15% or more has disease-modifying effect in Type 2 diabetes: Lancet

Dropping 15% or more of body weight can have a disease-modifying effect in Type 2 diabetes, find researchers in a new study.Thos is an outcome that is unattainable by any other glucose-lowering intervention. Therefore Weight loss should become a central focus of managing type 2 diabetes (T2D), since it has the potential to slow progress and even reverse many cases, and reduce complications.

We propose that for most patients with type 2 diabetes without cardiovascular disease, the main treatment focus should be managing the key underlying abnormality and driver of the disease: obesity,"states paper co-author Dr Ildiko Lingvay, University of Texas Southwestern Medical Center, Dallas, TX, USA. "Such an approach would have the added benefit of addressing not just high blood sugar, but other obesity-related complications, such as fatty liver, obstructive sleep apnoea, osteoarthritis, high blood pressure and an elevated blood fats profile, thus having a much greater impact on the person's overall health than just managing blood sugar alone."

"Treatment of obesity to achieve sustained loss of 15% body weight has been shown to have a major impact on type 2 diabetes progression and even result in diabetes remission in some patients," adds co-author Dr Priya Sumithran, University of Melbourne, Melbourne, VIC, Australia.

The evidence of the benefits of weight loss in T2D management comes from several sources. In the DiRECT trial which assessed an intensive lifestyle intervention in patients with overweight or obesity and T2D of less than 6 years' duration showed remission of T2D at 2 years in 70% of those who lost 15kg or more (with an average baseline weight of 100kg). Studies of obesity (bariatric) surgery have also shown both immediate and sustained benefits to patients with T2D and obesity – reducing the need for glucose lowering drugs within days of surgery and improving multiple indicators of health for the long-term.

The paper also discusses the various drug treatments available for weight management. Five agents (orlistat, phentermine–topiramate, naltrexone–bupropion, liraglutide 3·0 mg, and semaglutide 2·4 mg) are approved by one or more regulatory authorities worldwide for chronic weight management. Weekly semaglutide 2·4 mg was approved by the US Food and Drug Administration in June 2021. There are also many other drugs being developed, such as tirzepatide (which is an agonist of receptors for both glucagon-like-peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP)).

Studies of these new pharmaceuticals, such as semaglutide 2·4 mg and tirzepatide 15·0 mg, have reported that 15% of bodyweight can be readily lost in more than 25% of participants with T2D, and near normalisation of blood sugar control in most participants.

Most patients (40-70%) with type 2 diabetes will have one or more features of insulin resistance, meaning their T2D is likely driven by increasing body fat. "Key features that identify people in whom increasing body fat is a key mechanistic contributor to type 2 diabetes are the presence of central adiposity (fat around the waist), increased waist circumference, multiple skin tags, high blood pressure, and fatty liver disease," explains Dr Lingvay. "In this population, we propose a treatment goal of total weight loss of at least 15%, with the intention of not merely improving blood sugar control, but rather as the most effective way to disrupt the core pathophysiology of type 2 diabetes and thus change its course in the long term and prevent its associated metabolic complications."

The authors outline important considerations when redefining treatment goals for patients with T2D to focus on sustained weight loss. Firstly, the initiative should be driven by updating treatment guidelines to include substantial, sustained weight loss as a primary treatment target for patients with T2D.

Health systems should focus on the upstream benefits of reducing obesity in preventing or controlling T2D, rather than the higher costs of treating someone with advancing T2D and the cluster of complications that can come with the condition.

"Also vital is that medical practice management should refocus to effectively incorporate weight management for patients with type 2 diabetes," says Dr Lingvay. "Health-care providers, especially those managing people with diabetes routinely, should be trained and become experienced in all aspects of obesity management. Support staff should be trained to support patients through their weight-loss journeys, and practices should consider the need for specialised staff to deliver the educational component of the new treatment strategies that are proposed."

The authors conclude: "The time is right to consider the addition of substantial (ie, double-digit %) weight loss as a principal target for the treatment of many patients with type 2 diabetes. This approach would address the pathophysiology of the disease process for type 2 diabetes; recognise adipose tissue pathology as a key underlying driver of the continuum of obesity, type 2 diabetes, and cardiovascular disease; and reap metabolic benefits far beyond blood sugar control. Such a change in treatment goals would recognise obesity as a disease with reversible complications and require a shift in clinical care."