Building Competency in Diabetes Education THE ESSENTIALS

TREATMENT MODALITIES: PHARMACOLOGICAL THERAPIES | 6-43

Table 9. Antihyperglycemic agents: Thiazolidinediones (8,13,24,25,29,38,39,51, 105,106,108,109,110,111,112) Antihyperglycemic agent Therapeutic Considerations Adverse effects/cautions Despite the long-durability in glycemic

• Use in combination with insulin is not approved in Canada due to the increased risk of fluid retention and CHF. • Must do baseline LFT every 2 months for the first year, then periodically. Adverse effects • Peripheral edema (4 – 6%); CHF (1–3%); upper respiratory infection, headache, anemia (<1%) (dilutional effect associated with fluid retention and increased plasma volume). • Weight gain (2.0–2.5 kg) increases subcutaneous fat, not visceral fat; therefore has no effect on insulin resistance). Weight gain is generally dose dependent. • Associated with a statistically significant increased risk of bone loss and fractures in women treated with rosiglitazone/ pioglitazone (upper extremities [wrist, hand, forearm] and lower extremities [foot, ankle, tibia, fibula]); estimated fracture incidence of 0.78 per 100 patient-years for women age 55 years and older. TZD use is associated with lower bone mineral density. • May cause ovulation in premenopausal women with PCOS. Caution • If eGFR <60 mL/min/1.73m 2 • Dose adjustment not required but higher risk of edema. Contraindicated • People with CHF NYHA Class I to IV cardiac status; evidence of left ventricular dysfunction or serious hepatic impairment (ALT 2.5 x ULN); pregnancy • Discontinue if ALT >3 x ULN. Considerations in the elderly • Initiate at a lower dose and titrate slowly. • Higher risk of edema, weight gain, CHF with higher doses.

control and potential beta cell preservation, the increased risk of edema, weight gain, CHF, fractures in women, and concern regarding CV outcomes has limited the use of this class. Mechanism of action • Works at the cellular level to activate the peroxisome proliferator activated receptor-gamma receptors, increasing transcription of genes that regulate carbohydrate and lipid metabolism. Enhances insulin sensitivity, glucose transport and uptake in muscle cells, adipose tissue and liver. Inhibits hepatic glucose production, improves hepatic insulin sensitivity and decreases levels of circulating insulin. Benefits • ↓ A1C 0.7 – 0.9% •  FBG 2.2–3.3 mmol/L • Does not cause hypoglycemia. • Associated with long-lasting glycemic control versus metformin or sulfonylurea therapy. • CV protection: o Improves endothelial function and markers of inflammation. o Provides a small decrease in systolic and diastolic BP. o Decreases FFAs. • Can be used safely in mild to severe renal impairment, but caution as may lead to fluid retention. • •