Biguanides

Question 1

Biguanides MOA

Answer 1

• Primary MOA: glucose output from the liver (hepatic glucose production)
• Secondary MOA: peripheral muscle glucose sensitivity (glucose uptake and utilization)

Question 2

Biguanides: Site of Action

Answer 2

• LIVER and PERIPHERAL MUSCLE

Question 3

Biguanides Drug

Answer 3

Metformin

• IR 500mg, 850mg, 1000mg
• ER 500mg, 750mg, 1000mg

Question 4

Biguanides: Dosing

Answer 4

Initial dosing

• IR: 500mg BID or 850mg daily
• ER: 500-1,000mg with evening meal
• Minimal effective dose 500mg PO BID

Optimal dosing

• IR: 850-1,000mg BID
• ER: 1,000-2,000mg daily

2,000mg target dose for metformin

Renal dosing
- eGFR > 45 mL/min: No adjustment

Dose must be titrated SLOWLY to avoid GI side effects

• eGFR 30-45 mL/min: half dose, up to 1,000mg/day
• eGFR ≤ 30mL/min: Discontinue
• ARF: Discontinue until reversed

Question 5

Biguanides: Side effects

Answer 5

• Gastrointestinal
• Weight loss
• Lactic acidosis: <0.1/1000 patient year (Rare)

Question 6

Biguanides: Drug interactions

Answer 6

• Radiopaque contrast dyes

Question 7

Biguanides: Contraindications

Answer 7

• Hypersensitivity
• Renal disease/dysfunction
• Metabolic acidosis
• DKA
• Lactic acidosis
• Iodinated contrast
• Impaired liver function
• Hypoxemia
• Dehydration
• Sepsis
• Surgery

Question 8

Biguanides: Precautions

Answer 8

• Elderly
• Excessive alcohol use
• CHF requiring drug therapy

Question 9

Biguanides: Counseling points

Answer 9

• Take with food to decrease GI effects
• Start low, go slow
• Avoid alcohol use
• GI upset/diarrhea should decrease over time
• Could become Vitamin B12 deficiency (then take supplements)

ASK ABOUT: GI upset, weight loss and signs/symptoms of lactic acidosis (SOB, muscle cramping, tachycardia)

Question 10

Biguanides: Monitoring

Answer 10

• Renal Function (eGFR)

Time to peak effect: 6-8 weeks