What is the treatment for insulin resistance?

Insulin Resistance: Understanding and Treatment

Insulin resistance is a condition characterized by impaired cellular responsiveness to insulin, requiring comprehensive management through lifestyle modifications (weight loss, exercise) and pharmacotherapy (metformin as first-line), with treatment decisions guided by individual cardiovascular risk factors. 1

What is Insulin Resistance?

Insulin resistance occurs when cells in muscles, fat, and liver don't respond properly to insulin, leading to:

• Decreased insulin-dependent glucose disposal
• Impaired hepatic sensitivity to insulin
• Dysfunctional glucose homeostasis 2

This condition is associated with a "clustering" of cardiovascular risk factors including:

• Abdominal obesity
• Hypertension
• Dyslipidemia (high triglycerides, low HDL)
• Glucose intolerance
• Hyperinsulinemia 3

Treatment Approach

First-Line: Lifestyle Modifications

1. Weight Management:

   • Even modest weight loss (5-7% of initial body weight) significantly improves insulin sensitivity 1
   • Reduce energy intake by 500-1,000 calories per day from maintenance requirements 1

2. Dietary Recommendations:

   • Limit fat intake to less than 30% of total daily energy 1
   • Replace saturated fats with monounsaturated fats 1
   • Increase dietary fiber intake 1
   • Consider including plant stanols/sterols (2g daily) 1

3. Physical Activity:

   • Minimum 150 minutes/week of moderate-intensity exercise plus resistance training twice weekly 1
   • Moderate to high-intensity exercise improves insulin sensitivity more effectively than low-intensity exercise 1
   • Combining aerobic and resistance training provides greater improvement in glycemic control than either alone 1

Second-Line: Pharmacological Interventions

1. Metformin:

   • First-line pharmacological agent for insulin resistance 1
   • Starting dose: 500 mg once or twice daily
   • Maximum effective dose: 2,000-2,500 mg/day 1
   • As effective as lifestyle modification in participants with BMI ≥35 kg/m² and in younger participants aged 25–44 years 4
   • Particularly effective in individuals with history of gestational diabetes 4

2. Thiazolidinediones (e.g., Pioglitazone):

   • Improves insulin sensitivity in insulin-resistant patients 2
   • Enhances cellular responsiveness to insulin 2
   • Increases insulin-dependent glucose disposal 2
   • Improves hepatic sensitivity to insulin 2
   • In the IRIS trial, pioglitazone reduced the risk of stroke, myocardial infarction, and diabetes in patients with insulin resistance 4
   • Potential side effects include weight gain, edema, and fractures 4

3. SGLT2 Inhibitors:

   • Recommended for patients with type 2 diabetes, CKD, and eGFR ≥20 ml/min/1.73 m² 1
   • Can be initiated regardless of baseline HbA1c or metformin use 1

4. GLP-1 Receptor Agonists:

   • Recommended for patients who cannot use SGLT2 inhibitors 1
   • Can be added to SGLT2 inhibitors for additional glycemic control 1

Special Considerations

Cardiovascular Risk Management

• Moderate-intensity statin is recommended for all patients with diabetes and CKD for primary prevention of ASCVD 1
• High-intensity statin is recommended for patients with known ASCVD or multiple ASCVD risk factors 1
• Statin use increases risk of diabetes, but cardiovascular and mortality benefits exceed this risk 4

Monitoring and Assessment

• Regular monitoring of glycemia, blood pressure, cardiovascular risk, and lipids every 3-6 months 1
• For patients on insulin therapy, self-monitoring of blood glucose before meals and snacks, at bedtime, and occasionally after meals 1

Common Pitfalls to Avoid

1. Relying solely on standard weight reduction diets without structured support programs 1
2. Using very low calorie diets without a structured weight maintenance program 1
3. Therapeutic inertia (failing to intensify therapy despite suboptimal control) 1
4. Neglecting comorbidities in medication selection 1
5. Overemphasis on glycemic control alone, without addressing other cardiovascular risk factors 1
6. Overlooking vitamin B12 deficiency in long-term metformin users 1

By addressing insulin resistance through a combination of lifestyle modifications and appropriate pharmacotherapy, patients can significantly improve insulin sensitivity, reduce cardiovascular risk factors, and prevent or delay the progression to type 2 diabetes.