What are the usage indications, conditions, and dosages for all antidiabetic drugs, including the latest groups?

Comprehensive Guide to Antidiabetic Medications: Indications, Conditions, and Dosages

First-Line Therapy: Metformin

Metformin should be initiated as first-line therapy for most patients with type 2 diabetes due to its high efficacy, safety profile, low cost, minimal hypoglycemia risk, and potential cardiovascular benefits. 1

Indications and Dosing:

• Starting dose: 500 mg once or twice daily with meals
• Target dose: Titrate gradually to 1000 mg twice daily (maximum 2000-2550 mg/day)
• Extended-release formulation: 500-2000 mg once daily, improves GI tolerability and adherence 2
• Contraindications: eGFR <30 mL/min/1.73m²
• Dose adjustment: Consider dose reduction when eGFR <45 mL/min/1.73m²

Key Considerations:

• Monitor vitamin B12 levels, especially in patients with anemia or neuropathy
• Temporarily discontinue during severe illness, vomiting, or dehydration
• Common side effects: Gastrointestinal symptoms (dose-dependent)

Second-Line Therapy Options

SGLT2 Inhibitors

• Indications: Particularly beneficial for patients with established cardiovascular disease, heart failure, or chronic kidney disease 1
• Dosing: Varies by agent; restricted by eGFR
• Benefits: Cardiovascular protection, weight loss, low hypoglycemia risk
• Cautions: Risk of genital mycotic infections, volume depletion, diabetic ketoacidosis
• Special consideration: Recommended for most patients with type 2 diabetes and eGFR <60 mL/min/1.73m² without albuminuria and for those with albuminuria ≥200 mg/g 1

GLP-1 Receptor Agonists

• Indications: Particularly beneficial for patients with established cardiovascular disease or high cardiovascular risk, especially with obesity 1
• Administration: Subcutaneous injection (daily or weekly depending on agent)
• Benefits: High glucose-lowering efficacy, weight loss, low hypoglycemia risk
• Dosing examples:
  • Dulaglutide: Initially 0.75 mg once weekly, can increase to 1.5 mg once weekly
  • Liraglutide: Initially 0.6 mg once daily, increase to 1.2-1.8 mg once daily after one week
  • Semaglutide: Weekly injection with proven cardiovascular benefits 1

DPP-4 Inhibitors

• Indications: Alternative for patients who cannot tolerate other second-line agents
• Benefits: Moderate glucose-lowering efficacy, weight-neutral, well-tolerated, minimal hypoglycemia risk
• Cautions: Dose adjustment needed based on renal function (except linagliptin)
• Special considerations: Potential increased risk of heart failure with saxagliptin and alogliptin 1

Thiazolidinediones (TZDs)

• Indications: Alternative for patients with insulin resistance
• Benefits: High glucose-lowering efficacy, durability of effect
• Cautions: Weight gain, fluid retention, increased risk of heart failure, fracture risk
• Dosing: Varies by agent (pioglitazone, rosiglitazone)

Sulfonylureas

• Indications: Alternative when cost is a major concern
• Dosing examples:
  • Glimepiride: 1-8 mg once daily
  • Glipizide: 5-20 mg daily (divided doses)
  • Glyburide: 2.5-20 mg daily (divided doses)
• Cautions: Hypoglycemia risk, weight gain, possible cardiovascular concerns

Insulin Therapy

Indications for Immediate Insulin Initiation:

• HbA1c >10%
• Blood glucose >300-350 mg/dL
• Symptomatic hyperglycemia (polyuria, polydipsia, weight loss) 1, 3

Basal Insulin:

• Starting dose: 10 units or 0.1-0.2 units/kg/day
• Titration: Increase by 2-4 units every 3-4 days until fasting glucose 80-130 mg/dL 3
• Options: NPH, glargine, detemir, degludec

Mealtime Insulin:

• Indications: When basal insulin alone doesn't achieve target HbA1c
• Options: Rapid-acting analogs (lispro, aspart, glulisine) 4
• Dosing: Start with 4 units or 10% of basal dose at largest meal, titrate based on postprandial glucose

Treatment Algorithm

1. Initial therapy:

   • Start with metformin unless contraindicated
   • Begin at 500 mg once or twice daily, titrate to 1000 mg twice daily as tolerated

2. If HbA1c target not achieved after 3 months:

   • For patients with established ASCVD, heart failure, or CKD:
     • Add SGLT2 inhibitor or GLP-1 RA with proven cardiovascular benefit
   • For patients with obesity:
     • Prefer GLP-1 RA
   • For patients with cost concerns:
     • Consider sulfonylurea or TZD

3. For patients with HbA1c >9% at diagnosis:

   • Consider initial dual therapy with metformin plus a second agent

4. For patients with HbA1c >10%, glucose >300 mg/dL, or symptomatic:

   • Start insulin therapy (with or without other agents)

Special Considerations

Diabetic Kidney Disease:

• SGLT2 inhibitors recommended for patients with eGFR >20 mL/min/1.73m² regardless of albuminuria status 1
• GLP-1 RAs with proven cardiovascular benefits if SGLT2 inhibitors not tolerated

Cardiovascular Disease:

• Prioritize SGLT2 inhibitors and GLP-1 RAs with proven cardiovascular benefits
• Consider SGLT2 inhibitors specifically for heart failure

Monitoring:

• Evaluate response to therapy after 3 months
• Adjust therapy if HbA1c target not achieved
• Consider continuous glucose monitoring for patients on insulin

Common Pitfalls to Avoid

1. Delaying intensification when glycemic targets aren't met
2. Overlooking cardiovascular and renal benefits of newer agents
3. Inadequate dose titration of metformin (start low, go slow to minimize GI side effects)
4. Failing to discontinue metformin during acute illness or procedures with contrast dye
5. Not adjusting medication doses based on renal function
6. Overlooking vitamin B12 deficiency in long-term metformin users

By following this evidence-based approach to antidiabetic medication selection and dosing, clinicians can optimize glycemic control while minimizing risks and addressing comorbidities in patients with type 2 diabetes.