Is lasting remission feasible in the real-world setting? No!

In considering whether lasting remission of type 2 diabetes (T2DM) is feasible in the real-world setting, we must first consider what we mean by 'lasting' remission, and if it is feasible to achieve this for large numbers of people.Unfortunately, there is a lack of consensus internationally on how remission is defined.A systematic review of 178 studies of T2DM remission reported 266 different definitions of remission. 1The most recent consensus report from the American Diabetes Association defines remission as an haemoglobin A1c (HbA1c) <6.5% (48 mmol/mol) three months after cessation of glucose-lowering therapies. 2However, one aspect that such definitions ignore is the underlying pathophysiology of T2DM.Natural history data show that diabetes is a progressive disease.For example, the longest running study on the prevention of diabetes, the Da Qing study, reports that 80% of patients still go on to develop diabetes after 20 years. 3ne key means of achieving remission is lifestyle intervention and adherence to a low-energy diet (LED).Numerous studies have trialled an 800-900 calorie diet for 8-12 weeks through meal replacement. 4At year 1 remission in the DiRECT study was achieved in 46% of patients, dropping to 36% in year 2 and an estimated 7% in year 5 (data presented at Diabetes UK 2023).Remission in the Look Ahead study was 16% at year 1, and around 4% at year 4. 5 Long-term remission is clearly difficult to achieve, and in addition we must also consider that substantial weight re-gain following cessation of a LED is commonly reported in trials.This area is further complicated by methodological problems and reporting bias in weight maintenance data.Adherence to dietary interventions is challenging for various reasons.A number of circulating hormones are altered; these mediate appetite and encourage weight regain, increased hunger, increased appetite, and increased preference for energy-dense foods.Interventions such as bariatric surgery and glucagon-like peptide-1 (GLP-1) agonists target some of these responses.In relation to GLP-1 agonists, there are good supporting data.For example, in the SURMOUNT-2 study of 938Is lasting remission feasible in the real-world setting?No!