How is treatment deescalation done in a patient with type 2 diabetes (T2D) who has achieved good glycemic control?

Treatment Deescalation in Type 2 Diabetes

In patients with type 2 diabetes who achieve HbA1c levels below 6.5% on pharmacologic therapy, deescalation of treatment by reducing medication dosage or number of drugs is warranted to reduce harms, patient burden, and costs. 1

When to Deescalate Treatment

Primary Indication

• Deescalate when HbA1c falls below 6.5% on medication therapy 1, 2
• No clinical trials demonstrate that targeting HbA1c levels below 6.5% with pharmacologic therapy improves clinical outcomes 1, 2
• Achieving HbA1c below 6.5% with medications is associated with substantial harms, including increased risk of hypoglycemia and increased mortality in some studies 2

Supporting Evidence

• The ACCORD trial, which targeted HbA1c levels below 6.5%, was discontinued early due to increased overall and cardiovascular-related death and severe hypoglycemic events 2
• Pharmacologic treatment to achieve lower targets has not shown clinical benefits and may increase risks of adverse events 3, 2

How to Implement Deescalation

Step 1: Verify Glycemic Control

• Confirm that the low HbA1c is accurate and not an isolated reading 2
• Review recent HbA1c trends over the past 3-6 months 3

Step 2: Prioritize Which Medications to Reduce First

Discontinue medications gradually rather than all at once, particularly if the patient is on multiple agents 2

Priority order for medication reduction:

1. First: Eliminate medications with highest risk of hypoglycemia 2

   • Insulin (especially prandial insulin) 2, 4
   • Sulfonylureas 2, 4

2. Second: Reduce or eliminate other glucose-lowering agents 1

   • Consider keeping metformin as it has low hypoglycemia risk and cardiovascular benefits 1
   • Consider keeping SGLT2 inhibitors or GLP-1 receptor agonists if cardiovascular or renal benefits are present 1

Step 3: Gradual Dose Reduction Protocol

• For insulin: Reduce doses by 10-20% initially, then continue reducing based on glucose monitoring 1
• For sulfonylureas: Reduce dose by 50% or discontinue entirely given high hypoglycemia risk 2, 4
• For other oral agents: Reduce to lowest effective dose or discontinue based on individual medication 1

Step 4: Intensify Monitoring During Deescalation

• Monitor glucose levels more frequently during the discontinuation period 2
• Check fasting and postprandial glucose levels at least weekly initially 2
• Schedule follow-up HbA1c testing in 3 months to ensure glycemic control is maintained 2

Lifestyle Emphasis During Deescalation

Emphasize the continued importance of lifestyle modifications as medications are reduced 2

• Diet: Maintain dietary modifications that contributed to good control 3
• Physical activity: Aim for at least 150 minutes per week of moderate-intensity exercise 3
• Weight management: Continue weight maintenance or modest weight reduction (5-10% of body weight if overweight) 3

Special Populations Requiring Deescalation

Elderly Patients (≥80 years)

• Deescalation is particularly appropriate as the focus should be on avoiding hypoglycemia rather than tight glycemic control 2
• Performance measures should not have any HbA1c targets for older adults 1

Patients with Limited Life Expectancy

• Those with serious comorbid conditions, end-stage disease complications, or cognitive impairment 1
• The goal should be to minimize symptoms rather than achieve a specific HbA1c target 1

Patients with Multiple Comorbidities

• Renal failure, liver failure, advanced microvascular or macrovascular complications 1
• The harms of intensive HbA1c targets outweigh the benefits in these populations 1

Monitoring After Deescalation

Short-term Monitoring (First 3-6 months)

• HbA1c every 3 months to ensure control is maintained 2
• More frequent glucose monitoring if patient was on insulin or sulfonylureas 2
• Educate patient about symptoms of hyperglycemia that would warrant reassessment 2

Long-term Monitoring

• HbA1c every 3-6 months once stable 3
• Continue monitoring for diabetes-related complications 3
• Address other cardiovascular risk factors including blood pressure and lipid management 3

Common Pitfalls to Avoid

Clinical Inertia in Reverse

• Do not maintain unnecessary medications when HbA1c is below 6.5% 1, 2
• Continuing intensive therapy increases hypoglycemia risk without proven benefit 1, 2

Inadequate Patient Education

• Educate patients that deescalation is appropriate medical management, not treatment failure 2
• Explain that diabetes is progressive and some patients may need to restart medications in the future 2

Neglecting Lifestyle Maintenance

• Do not assume medications can be reduced without maintaining lifestyle modifications 3, 2
• Patients who achieved good control primarily through lifestyle modifications have higher likelihood of maintaining control after medication discontinuation 2

Abrupt Discontinuation

• Avoid stopping all medications simultaneously 2
• Gradual reduction allows for monitoring and adjustment 2

When NOT to Deescalate

• HbA1c remains at or above 6.5% - maintain current therapy or intensify 1
• Recent diagnosis with short disease duration - may benefit from early intensive control for legacy effect 1
• Medications providing cardiovascular or renal protection (SGLT2 inhibitors, GLP-1 receptor agonists) in high-risk patients - consider maintaining these even with low HbA1c 1

Cost and Quality of Life Considerations

Deescalation reduces patient burden and costs of treatment 1

• Decreases medication burden and associated costs 2
• Improves quality of life by reducing pill burden and potential side effects 2
• Avoids unnecessary medication exposure when glycemic control is already excellent 2
• Reduces risk of hypoglycemia, which is associated with reduced quality of life, fear and anxiety, and reduced productivity 5, 6