From the Guidelines
Medical treatment for insulin resistance typically begins with lifestyle modifications, but medications are often necessary, with metformin being the first-line medication, as recommended by the American Diabetes Association standards of medical care in diabetes 1.
Key Considerations
- Metformin is usually started at 500mg once daily with meals, then gradually increased to 1000mg twice daily as tolerated to minimize gastrointestinal side effects.
- Thiazolidinediones like pioglitazone (15-45mg daily) can be added if metformin alone is insufficient.
- For patients with concurrent type 2 diabetes, GLP-1 receptor agonists such as semaglutide (weekly injection starting at 0.25mg and increasing to 0.5-1mg) or SGLT-2 inhibitors like empagliflozin (10-25mg daily) may be beneficial, as suggested by recent studies 1.
Mechanisms of Action
- Metformin reduces liver glucose production and improves insulin sensitivity.
- Thiazolidinediones enhance insulin sensitivity in fat and muscle tissue.
- GLP-1 agonists improve insulin secretion and reduce appetite.
- SGLT-2 inhibitors increase glucose excretion through urine.
Individualized Treatment
- Treatment should be individualized based on comorbidities, with regular monitoring of blood glucose levels, HbA1c, and potential side effects.
- Patients should continue lifestyle modifications including regular exercise (150 minutes weekly of moderate activity) and a diet low in refined carbohydrates even while on medication therapy, as recommended by the American Diabetes Association 1.
Lifestyle Modifications
- Modest weight loss has been shown to improve insulin resistance, and weight loss is recommended for all overweight and obese individuals who have or are at risk for diabetes 1.
- Physical activity and behavior modification are important components of weight loss programs and are most helpful in maintenance of weight loss.
From the FDA Drug Label
Clinical studies demonstrate that ACTOS improves insulin sensitivity in insulin-resistant patients. ACTOS enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, improves hepatic sensitivity to insulin, and improves dysfunctional glucose homeostasis
- Medical treatments for insulin resistance include:
- Pioglitazone (ACTOS): improves insulin sensitivity, enhances cellular responsiveness to insulin, and increases insulin-dependent glucose disposal 2
- Key effects of pioglitazone on insulin resistance:
- Improves hepatic sensitivity to insulin
- Improves dysfunctional glucose homeostasis
- Lowers plasma glucose concentrations, plasma insulin levels, and HbA1c values in patients with type 2 diabetes 2
From the Research
Medical Treatments for Insulin Resistance
The following medical treatments are available for insulin resistance:
- Metformin: a biguanide that improves peripheral sensitivity to insulin, reduces gastrointestinal glucose absorption, and hepatic glucose production 3, 4, 5, 6
- Thiazolidinediones (TZDs): pioglitazone and rosiglitazone, which directly lower insulin resistance 3
- Glucagon-like peptide-1 (GLP-1) receptor agonists: exenatide, liraglutide, albiglutide, dulaglutide, and lixisenatide, which improve glucose-dependent insulin release, suppress glucagon release, and decrease the rate of gastric emptying 7
- Other therapeutic concepts: new peroxisome proliferator-activated receptor agonists, incretin mimetics, sodium glucose cotransporter inhibitors, and modulators of energy metabolism 6
Mechanisms of Action
These treatments work by:
- Improving insulin sensitivity: metformin, TZDs, and GLP-1 receptor agonists 3, 4, 5, 7
- Reducing glucose production in the liver: metformin and GLP-1 receptor agonists 3, 4, 7
- Suppressing glucagon release: GLP-1 receptor agonists 7
- Decreasing the rate of gastric emptying: GLP-1 receptor agonists 7
Benefits and Considerations
These treatments have been shown to:
- Improve glycemic control: metformin, TZDs, and GLP-1 receptor agonists 3, 4, 5, 7
- Reduce cardiovascular risk factors: metformin, TZDs, and GLP-1 receptor agonists 3, 5, 7
- Have beneficial effects on serum lipid profiles: metformin and GLP-1 receptor agonists 4, 7
- Have potential gastrointestinal side effects: metformin and GLP-1 receptor agonists 4, 7