Building Competency in Diabetes Education THE ESSENTIALS

TREATMENT MODALITIES: PHARMACOLOGICAL THERAPIES | 6-22

Table 1. First-Line Treatment: Biguanides (13, 24, 25, 38-43, 44) Biguanides

Therapeutic Considerations

INDICATION: First line of treatment for all people with type 2 diabetes (unless contraindicated) Mechanism of action • Increase insulin sensitivity in liver and peripheral tissues

Adverse effects • 30% of individuals experience GI side effects (diarrhea, nausea, vomiting, abdominal bloating, flatulence, anorexia, metallic taste). • Symptoms are transient and improve with time (1-2 weeks). • 5–10% of people are unable to tolerate due to substantial GI side effects. • Lactic acidosis is rare (0.03/1000 patient years; 0.015 fatal cases/1,000 patient years); more likely to occur in people with renal insufficiency, alcohol or liver disease. Hold dose in hypoxic states, shock, severe infection or septicemia. o Caution against excessive alcohol intake (acute or chronic). Caution • Two-fold increase in incidence of vitamin B12 deficiency in people on long-term treatment (16%). Monitor serum B12 levels at least every 1- 2 years, and in the presence of anemia, impaired proprioception or peripheral neuropathy. B12 or calcium supplementation may be needed. • Dose may need to be held in the following situations due to increased risk of acute renal failure: o Radiological studies with IV contrast: Hold dose the day of procedure and resume in 2–3 days once renal function has returned to normal. o Surgery associated with restricted intake of food and fluids: Hold 2 days before surgery and restart once intake/renal function is normal. Dose adjustment • Decrease dose to 500-1,000 mg if eGFR 30- 45mL/min/1.73m 2 , when renal function is not known, or if serum creatinine levels ≥ 136 mmol/L (males), ≥12 4 mmol/L (females). • Rationale: metformin is renally excreted. Contraindicated • eGFR <30 mL/min/1.73m 2 or hepatic failure • Acute or chronic excessive alcohol intake

(muscle and fat) by activation of AMP-activated protein kinase.

• Improve glucose transport across the cell membrane,

improving glucose uptake and utilization. Inhibit hepatic glucose production (gluconeogenesis)

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in the fasting and postprandial state.

Benefits •

Targets fasting and postprandial BG

• ↓ A1C 1.0% •

Hypoglycemia rare

Weight neutral

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Durable BG lowering Long-term safety data Low cost/adverse effects CV benefit: Reduction in MI in overweight individuals with type 2 diabetes Can improve ovulation in women with PCOS May lower cancer risk in older people with diabetes,

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