What is diabetes in remission?

What is Diabetes in Remission?

Diabetes remission occurs when a patient no longer meets the diagnostic criteria for diabetes (HbA1c <48 mmol/mol or <6.5%) without receiving glucose-lowering medication, confirmed over a sustained period of at least 3-6 months. 1, 2

Core Definition

Remission requires achieving blood glucose levels below the diabetes diagnostic threshold while off all glucose-lowering medications (except metformin in some definitions), maintained for a minimum duration. 1

Specific Diagnostic Criteria

• HbA1c must be <48 mmol/mol (<6.5%) measured at least 3 months after stopping glucose-lowering medications 2
• Some definitions allow HbA1c <42 mmol/mol (<6.0%) as a more stringent threshold for complete remission 1
• Fasting plasma glucose <7 mmol/l can also define remission when HbA1c is unavailable 1
• Confirmation requires sustained normal glucose levels for 6-12 months to distinguish remission from temporary improvement 1

Critical Distinction: Medication Withdrawal Required

For patients already taking glucose-lowering drugs, a therapeutic trial of withdrawing medication is necessary to ascertain true remission, with protocols for re-introduction if glucose levels rise. 1

• Metformin may be continued in some remission definitions, as it is considered primarily a preventive agent rather than glucose-lowering therapy 3
• All other diabetes medications (sulfonylureas, insulin, GLP-1 agonists, SGLT2 inhibitors) must be discontinued 1

How Remission is Achieved

Weight Loss as Primary Driver

The main contributor to remission is substantial weight loss (typically >10-15 kg), which removes ectopic fat from the liver and pancreas, restoring beta cell function. 1, 4

• Weight loss of as little as 4 kg can ameliorate hyperglycemia, with benefits appearing within weeks to months 5
• Structured programs with total diet replacement achieve the highest remission rates: 46-61% at 1 year in high-quality RCTs 1
• The mechanism is independent of diet type—what matters is achieving and maintaining sufficient weight loss 1

Predictors of Successful Remission

Remission is most achievable in patients with:

• Diabetes duration <2-6 years (remission rates up to 75% vs. 20-22% with 8+ years duration) 1
• Lower baseline HbA1c at diagnosis 5, 4
• Minimal or no glucose-lowering medication requirements 4
• Preserved beta cell capacity 4

Clinical Significance and Monitoring

Why the Diagnostic Threshold Matters

The HbA1c cut-off of 48 mmol/mol (6.5%) was defined by WHO as the level where diabetes-specific microvascular complications begin to emerge. 1

• Many people in remission remain in the prediabetes range (HbA1c 42-47 mmol/mol), where cardiovascular disease risk still exists 1
• However, achieving HbA1c <42 mmol/mol (<6.0%) through diet restriction has not shown the mortality concerns seen with aggressive medication-based lowering in longstanding disease 1

Duration and Relapse Risk

Remission can be maintained for years if weight loss is sustained, but relapse is common with weight regain. 4, 6

• Remission remains possible for at least 10 years in most individuals, though it becomes progressively harder as disease duration increases and beta cell function declines 5, 4
• In the DiRECT trial, 36% maintained remission at 2 years with mean weight loss of 7.6 kg 1
• Ongoing monitoring is essential as relapse can occur, requiring reinitiation of treatment 1, 2

Important Caveats

Not a Cure

Remission does not mean diabetes is cured—it represents a state of inactive disease that requires sustained lifestyle changes to maintain. 4, 2

• The underlying pathophysiology (insulin resistance, beta cell dysfunction) remains present 4
• Weight regain typically leads to diabetes recurrence 4, 6

Confirmation Period is Critical

A single normal HbA1c reading off medications is insufficient—confirmation over 6-12 months is required for legal, insurance, and clinical reclassification purposes. 1

Type 1 Diabetes Exception

The term "remission" can also apply to type 1 diabetes during the "honeymoon period" after initial presentation, when patients briefly return to normoglycemia without continuous therapy. 1

• This is a temporary phenomenon in type 1 diabetes, distinct from the potentially sustained remission achievable in type 2 diabetes 1

Practical Implementation

Early intervention dramatically improves remission success—weight management should be offered to all people with type 2 diabetes as soon as possible after diagnosis, or even at the prediabetes stage. 5, 4

• Raising awareness among patients and providers that remission is possible enables earlier, more effective intervention 4
• The greatest challenge is maintaining long-term weight loss, requiring ongoing support and monitoring 4