What to do if Hemoglobin A1c (HbA1c) is normal on metformin (Glucophage) but insulin levels are elevated?

Managing Elevated Insulin Levels with Normal A1c on Metformin

If your A1c is normal on metformin but your insulin levels are elevated, you should consider adding a GLP-1 receptor agonist to your treatment regimen to address insulin resistance while maintaining glycemic control. 1

Understanding the Problem

Elevated insulin levels despite normal A1c on metformin indicate:

• Persistent insulin resistance
• Compensatory hyperinsulinemia
• Metformin is controlling glucose levels but not fully addressing insulin resistance

Treatment Algorithm

Step 1: Evaluate Current Therapy

• Confirm metformin is at optimal dose (typically up to 2,000 mg daily)
• Verify A1c is truly in target range (<7% for most adults)
• Assess for symptoms of insulin resistance (weight gain, difficulty losing weight)

Step 2: Intensify Lifestyle Modifications

• Focus on weight reduction (aim for 5-10% weight loss if overweight/obese)
• Increase physical activity to 30-60 minutes of moderate exercise at least 5 days/week
• Emphasize low-glycemic index diet with reduced carbohydrates
• Reduce consumption of sugar-added beverages and processed foods 1

Step 3: Medication Adjustments

For patients with normal A1c but elevated insulin levels:

1. First-line approach: Add a GLP-1 receptor agonist (if 10 years or older)

   • Provides significant insulin-sensitizing effects
   • Promotes weight loss
   • Low hypoglycemia risk
   • Has cardiovascular protective effects 2, 1

2. Alternative approach: Consider SGLT2 inhibitor

   • Moderate effect on insulin sensitivity
   • Promotes weight loss
   • Provides cardiovascular and renal protection 1

3. If cost is prohibitive: Consider DPP-4 inhibitors

   • Weight neutral
   • Low hypoglycemia risk
   • May help modestly with insulin resistance 1

Monitoring and Follow-up

• Recheck insulin levels in 3 months to assess response
• Continue monitoring A1c every 3 months to ensure maintained glycemic control
• Track weight and other metabolic parameters (lipids, blood pressure)
• Adjust therapy based on response 1

Important Considerations

• Do not discontinue metformin - it remains the foundation of therapy and helps with insulin sensitivity 2
• Avoid sulfonylureas - they can increase insulin levels further and cause weight gain
• Insulin therapy is not indicated when A1c is at target, as it would likely worsen hyperinsulinemia 3
• Regular monitoring of both glucose and insulin levels is essential to track progress

Common Pitfalls to Avoid

• Focusing only on A1c: Normal A1c with high insulin levels still represents metabolic dysfunction that needs addressing
• Ignoring weight management: Weight reduction is crucial for improving insulin sensitivity
• Delaying therapy intensification: Adding a second agent should not be delayed if insulin levels remain elevated despite lifestyle changes 1
• Using medications not FDA-approved: Stick to approved medications for diabetes management unless in a research setting 2

By following this approach, you can address the underlying insulin resistance while maintaining good glycemic control, potentially reducing long-term cardiovascular and metabolic risks.