Management of Insulin Resistance
Insulin resistance is best managed with lifestyle modifications as the foundation, with metformin as the first-line pharmacological therapy when lifestyle changes alone are insufficient to achieve glycemic targets. 1
Initial Approach to Management
Lifestyle Modifications
- Begin with comprehensive lifestyle modifications including dietary changes, increased physical activity, and weight loss for overweight/obese individuals 1
- Intensive lifestyle interventions are more effective than modest changes - significant improvements in insulin sensitivity require substantial changes in exercise habits and diet 2
- Target weight loss of 5-10% of body weight for overweight/obese individuals, which can significantly improve insulin sensitivity 1
- Implement regular aerobic exercise (at least 150 minutes per week of moderate-intensity activity) as improved aerobic fitness appears to be a major determinant of enhanced insulin sensitivity 2
- Increase dietary fiber intake while reducing refined carbohydrates and saturated fats 2
Pharmacological Management
First-Line Therapy
- Metformin is the preferred first-line pharmacological agent for insulin resistance, particularly in patients with type 2 diabetes 1
- Metformin improves insulin sensitivity by decreasing hepatic glucose production, decreasing intestinal glucose absorption, and increasing peripheral glucose uptake and utilization 3
- Start metformin at a low dose (500 mg daily) with gradual titration (increasing by 500 mg every 1-2 weeks) to minimize gastrointestinal side effects, targeting an ideal dose of 2000 mg daily in divided doses 1
- Clinical studies demonstrate that metformin significantly reduces fasting plasma glucose (by approximately 53 mg/dL) and HbA1c (by approximately 1.4%) compared to placebo 3
Second-Line Options
- If glycemic targets are not achieved after 3 months of metformin therapy, consider adding one of the following agents 1:
- Thiazolidinediones (TZDs) - particularly effective for insulin resistance and may be more beneficial in patients with higher BMIs 1
- GLP-1 receptor agonists - associated with weight reduction, which may further improve insulin sensitivity 1
- DPP-4 inhibitors - weight neutral option 1
- Sulfonylureas - effective but may cause weight gain 1
- Basal insulin - particularly for patients with significantly elevated HbA1c (>9%) 1
Special Considerations
Severe Hyperglycemia
- For patients presenting with significant hyperglycemic symptoms, markedly elevated plasma glucose (>300-350 mg/dL), or HbA1c ≥10%, consider insulin therapy from the outset 1
- Once symptoms are relieved and glucose control improves, it may be possible to taper insulin partially or entirely and transition to non-insulin therapies 1
Age-Related Considerations
- In older adults (≥65-70 years), focus on drug safety when selecting treatments 1
- Prioritize strategies that minimize hypoglycemia risk, heart failure, renal dysfunction, bone fractures, and drug-drug interactions 1
- Less stringent glycemic targets (HbA1c <7.5-8.0%) may be appropriate for elderly patients with long-standing or complicated disease 1
- For younger, healthier patients with longer life expectancy, target lower glycemic goals (HbA1c <6.5-7.0%) to prevent long-term complications 1
Weight Considerations
- For obese patients (approximately 80% of those with type 2 diabetes), intensive lifestyle intervention should be emphasized 1
- GLP-1 receptor agonists are particularly beneficial due to their association with weight reduction 1
- Consider bariatric surgery for severe obesity, which can rapidly resolve insulin resistance and type 2 diabetes in many patients 1
- For lean patients with insulin resistance, consider the possibility of latent autoimmune diabetes in adults (LADA) 1
Pregnancy
- Insulin is the preferred medication for treating hyperglycemia in pregnancy as it does not cross the placenta to a measurable extent 1
- Metformin and other oral agents should generally be avoided during pregnancy unless specifically indicated 1
- Target fasting glucose <95 mg/dL and either one-hour postprandial <140 mg/dL or two-hour postprandial <120 mg/dL 1
Monitoring and Follow-up
- Monitor HbA1c every 3 months until target is achieved, then at least twice yearly 1
- Assess for improvement in markers of insulin resistance including fasting glucose, lipid profile, and blood pressure 1
- Evaluate for medication side effects and adjust therapy as needed 1
- Comprehensive cardiovascular risk reduction must remain a major focus of therapy 1