Can Weight Loss Lead to Real Remission for Type 2 Diabetes?

The possibility of type 2 diabetes (T2D) remission has been widely debated in recent years, primarily due to studies investigating the effects of calorie restriction and weight loss on glycemic control. However, experts warn that achieving normal blood glucose and glycated hemoglobin levels does not necessarily mean disease reversal.

“At the time of diagnosis, approximately 50% of beta-cell function is already compromised. Many of these cells die through apoptosis and cannot be recovered,” said Luciano Giacaglia, MD, PhD, endocrinologist and coordinator of T2D and prediabetes at the Brazilian Diabetes Society, in an interview with Medscape’s Portuguese edition.

“When discussing remission, it’s crucial to differentiate between temporary control from a real reversal of the disease,” he added.

Defining Remission

The term “remission,” commonly used in clinical research, is controversial. According to Giacaglia, this can create a misleading impression of a cure for cancer. “Remission is defined as maintaining blood glucose levels below 6.5% without the use of medication. However, this does not imply that the patient is free from metabolic complications. Pancreatic dysfunction and insulin resistance continue to pose constant challenges.

Although T2D progression can be slowed, complete reversal is not yet achievable. Certain classes of medications, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists, can delay disease progression, but none offer a definitive cure. These treatments slow beta-cell decline and postpone insulin dependence, but they do not prevent disease progression, explained Giacaglia.

In addition to the difficulty in maintaining glycemic control, weight loss does not guarantee the restoration of pancreatic function.

“The human pancreas has a limited capacity for regeneration. Unlike certain animals, such as rats, humans lack germ cells in pancreatic islets that could develop into new beta cells,” Giacaglia noted. Thus, even with effective strategies to reduce insulin resistance, T2D continues to progress in most individuals.

Clinical Evidence

DiRECT, a clinical trial conducted in the United Kingdom, evaluated the effectiveness of a very low-calorie diet (825-853 kcal/d) for up to 5 months, followed by dietary reintroduction and continued support for weight maintenance.

After 12 months, 46% of the participants in the intervention group achieved remission compared with 4% in the control group. However, only 26% of patients maintained remission without medication after 5 years.

Wellington Santana da Silva Júnior, MD, PhD, director of the Department of Diabetes Mellitus at the Brazilian Society of Endocrinology and Metabolism, emphasized weight loss as a key factor for improving glycemic control.

Patients who lost > 15 kg had an 86% remission rate, while those who lost 5-10 kg achieved a 34% remission rate. However, he cautioned that long-term data show that most patients struggle to sustain these results.

Another study examined the effects of dapagliflozin, an SGLT2 inhibitor, combined with calorie restriction. The clinical trial, conducted in China, included 328 patients and reported a 44% remission rate in the treatment group vs 28% in the placebo group.

Giacaglia urged caution in interpreting these findings. “The pathophysiology of T2D differs between Eastern and Western populations. We are dealing with distinct diseases. Additionally, this study focused solely on blood glucose levels without assessing pancreatic function. If glucose levels are the only criterion, any therapeutic class can achieve this outcome,” he explained.

Giacaglia also noted the difficulty in duplicating these results in clinical practice. “These studies are highly controlled with rigorous monitoring and continuous support. In real-world settings, maintaining a restrictive diet is a major challenge,” he emphasized.

“The body responds to weight loss by lowering basal metabolism and increasing hunger, making it extremely difficult to maintain results,” da Silva Júnior told Medscape’s Portuguese edition. He emphasized the need for multidisciplinary support, including medical, nutritional, and psychological guidance, to improve adherence.

Questioning the Term

Despite these advances, T2D remission remains elusive in most patients. Furthermore, studies cannot evaluate pancreatic beta-cell regeneration in humans, as such analyses are limited to in vitro models and laboratory animals. Thus, “remission” can be misleading, as there is no guarantee of recovery of pancreatic function when it reflects only temporary improvement in glycemic parameters.

Not all patients respond to calorie restriction. “Patients with a shorter time since diagnosis (preferably less than 5 years), who are overweight or obese, do not require insulin, and maintain preserved C-peptide levels have the best chance of success,” da Silva Júnior said.

Patients with long-term diabetes, autoimmune forms of the disease (such as type 1 diabetes), or severe insulin deficiency are unlikely to benefit from this treatment.

Giacaglia emphasized the importance of early diagnosis, particularly in the prediabetes stage. “Studies show that in prediabetes, there is a 20%-30% loss of beta cells. If we want to discuss remission, the ideal time to intervene is during prediabetes.”

He also questioned the use of the term “remission,” which can falsely imply that the disease is resolved. “We know that this is not true. Many patients who undergo bariatric surgery, for example, develop diabetes again after the surgery. There is no cure — only a delay in disease progression,” Giacaglia concluded.

This story was translated from Medscape’s Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.