What is the treatment for insulin resistance?

Treatment for Insulin Resistance

The most effective treatment for insulin resistance is a structured intensive lifestyle program that includes reduced energy intake, regular physical activity, and weight loss of 5-7% of starting weight. 1

Lifestyle Modifications

Diet

• Reduce total energy intake by 500-1,000 calories per day from estimated maintenance requirements 1
• Limit fat intake to less than 30% of total daily energy 1
• Replace saturated fats with monounsaturated fats or carbohydrates 1
• Increase dietary fiber intake 1
• Incorporate 2-3 servings of plant stanols/sterols (2g) daily to lower cholesterol 1
• Consider including two or more servings of fish per week for n-3 polyunsaturated fats 1
• Focus on nutrient-dense foods and reduce consumption of calorie-dense, nutrient-poor foods 2

Physical Activity

• Implement at least 150 minutes per week of moderate-intensity aerobic exercise 2, 3
• Add resistance training twice weekly 2
• Aim for improved aerobic fitness, which appears to be a major determinant of improved insulin sensitivity 3

Pharmacological Interventions

First-Line Medication

• Metformin is the preferred initial pharmacological agent for insulin resistance 1, 2
  • Starting dose: 500 mg once or twice daily
  • Maximum effective dose: 2,000-2,500 mg/day
  • Contraindicated when eGFR <30 ml/min/1.73m² 2
  • Use with caution when eGFR <45 ml/min/1.73m² 2

Additional Medications Based on Comorbidities

• For patients with chronic kidney disease (CKD) and eGFR ≥20 ml/min/1.73m²: SGLT2 inhibitors 2
• For patients with cardiovascular risk: GLP-1 receptor agonists with proven cardiovascular benefit 2
• For severe insulin resistance: Thiazolidinediones (pioglitazone) 4
  • Improves insulin sensitivity by enhancing cellular responsiveness to insulin
  • Decreases insulin resistance in muscle and adipose tissue
  • Inhibits hepatic gluconeogenesis
  • Dosing: 15-45 mg once daily

Monitoring and Follow-up

• Regular assessment of glycemia every 3-6 months 2
• Monitor for medication side effects:
  • Metformin: vitamin B12 deficiency with long-term use 2
  • Pioglitazone: weight gain, edema, potential heart failure risk 4
• Assess cardiovascular risk factors including blood pressure and lipid profile 2

Special Considerations

For Severe Insulin Resistance

• If HbA1c >10% or fasting glucose >250 mg/dL, consider initiating insulin therapy 2
• Initial dose of basal insulin: 0.1-0.2 units/kg/day (approximately 10 units) 2
• Continue metformin concurrently with insulin therapy to limit weight gain 2

For Patients with Obesity

• More intensive lifestyle intervention is necessary for meaningful improvements in insulin sensitivity 3
• Consider structured programs with frequent participant contact similar to the Diabetes Prevention Program 1
• For BMI ≥35 kg/m², gastric reduction surgery may be considered 1

Common Pitfalls to Avoid

• Therapeutic inertia - not intensifying therapy despite suboptimal control 2
• Overemphasis on glycemic control without addressing other cardiovascular risk factors 2
• Relying solely on standard weight reduction diets without structured support programs 1
• Using very low calorie diets without a structured weight maintenance program 1

The evidence strongly suggests that modest lifestyle changes are insufficient to improve insulin sensitivity significantly. Instead, intensive lifestyle modifications with structured programs that produce meaningful improvements in aerobic fitness and weight loss are necessary for effective treatment of insulin resistance 3.