What are the treatment options for managing type 1 and type 2 diabetes with medications such as insulin (e.g. glargine, aspart), metformin, sulfonylureas (e.g. glimepiride), DPP-4 inhibitors (e.g. sitagliptin), GLP-1 receptor agonists (e.g. liraglutide), and SGLT2 inhibitors (e.g. empagliflozin)?

Treatment Options for Managing Type 1 and Type 2 Diabetes

For patients with type 2 diabetes, a combination of metformin and SGLT2 inhibitors should be used as first-line therapy, with additional agents added based on comorbidities, particularly GLP-1 receptor agonists for patients with cardiovascular disease risk, while type 1 diabetes requires insulin therapy as the foundation of treatment. 1

Type 1 Diabetes Management

• Insulin therapy is the cornerstone and only effective treatment for type 1 diabetes, as these patients have absolute insulin deficiency 1
• Multiple daily injections with basal insulin (glargine, detemir) and prandial insulin (aspart, lispro) or continuous subcutaneous insulin infusion are the standard approaches 1
• Insulin dosing should be individualized based on blood glucose monitoring, with typical starting doses of 0.5 units/kg/day, divided between basal and bolus insulin 2
• Hypoglycemia is a significant risk with insulin therapy, requiring careful monitoring and dose adjustment 2

Type 2 Diabetes Management

First-Line Therapy

• Metformin remains the preferred first-line agent for most patients with type 2 diabetes due to its efficacy, safety, low cost, and potential cardiovascular benefits 1
• Dose adjustments are required when eGFR is <45 ml/min/1.73 m², and metformin should be discontinued when eGFR is <30 ml/min/1.73 m² 1
• SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) should be added as first-line therapy alongside metformin for patients with eGFR ≥20 ml/min/1.73 m² 1

Second-Line and Add-on Therapy Options

• GLP-1 receptor agonists (liraglutide, semaglutide, dulaglutide) are preferred add-on agents, especially for patients with established cardiovascular disease or high cardiovascular risk 1
• GLP-1 receptor agonists provide significant glycemic efficacy (HbA1c reduction of 1-1.5%), promote weight loss, and have demonstrated cardiovascular benefits 1, 3
• Dual GIP/GLP-1 receptor agonists (tirzepatide) offer even greater efficacy for glycemic control and weight loss 1, 4
• DPP-4 inhibitors (sitagliptin) can be considered when GLP-1 receptor agonists are not tolerated or injectable therapy is declined 1
• Sulfonylureas (glimepiride) may be used as lower-cost alternatives but carry higher risks of hypoglycemia and weight gain 1, 5
• Thiazolidinediones should be avoided in patients with heart failure risk 6

Special Populations and Considerations

• For patients with CKD:

  • Metformin requires dose adjustment when eGFR is 30-44 ml/min/1.73 m² and discontinuation when <30 ml/min/1.73 m² 1
  • SGLT2 inhibitors provide kidney protection and can be initiated when eGFR is ≥20 ml/min/1.73 m² 1
  • GLP-1 receptor agonists are preferred when additional glycemic control is needed 1

• For patients with established cardiovascular disease:

  • SGLT2 inhibitors and GLP-1 receptor agonists should be prioritized due to proven cardiovascular benefits 1, 4
  • SGLT2 inhibitors are particularly beneficial for patients with heart failure 1, 4

• For patients with severe hyperglycemia (HbA1c ≥10%):

  • Consider immediate insulin therapy, possibly in combination with oral agents 1
  • Once glycemic control improves, insulin may be tapered and oral agents continued 1

• For elderly patients or those with cost concerns:

  • Metformin and sulfonylureas remain cost-effective options but require careful monitoring for hypoglycemia with sulfonylureas 1, 7
  • Consider discontinuing basal insulin in well-controlled patients who have other effective oral medications 8

Combination Therapy Approach

• Combination therapy targeting different pathophysiological defects is often necessary for optimal glycemic control 9
• Metformin + SGLT2 inhibitor combination addresses insulin resistance and promotes glucose excretion 1
• Adding a GLP-1 receptor agonist targets postprandial glucose excursions and provides additional benefits for weight and cardiovascular risk 1, 3
• Insulin therapy should be considered when combination oral/injectable therapy fails to achieve glycemic targets 1

Monitoring and Dose Adjustments

• HbA1c should be monitored every 3 months until target is achieved, then at least twice yearly 6
• Kidney function should be monitored at least annually for patients on metformin with normal function, and every 3-6 months when eGFR is <60 ml/min/1.73 m² 1
• SGLT2 inhibitors require monitoring for genital mycotic infections, diabetic ketoacidosis, and volume depletion 6
• Insulin doses should be adjusted based on blood glucose monitoring patterns, with attention to hypoglycemia risk 2

Medication Interactions and Precautions

• Insulin combined with sulfonylureas significantly increases hypoglycemia risk 2
• SGLT2 inhibitors may need temporary discontinuation during acute illness or surgical procedures 6
• GLP-1 receptor agonists may require insulin dose reduction when used in combination therapy 1, 3
• Metformin should be temporarily discontinued with contrast studies or during acute illness with dehydration risk 1