Medicine for Type II Diabetes

Metformin (Glucophage®):

• decreases hepatic (liver) glucose production
• decreases intestinal absorption of glucose
• improves insulin sensitivity (increases uptake of glucose into cells)

Dosage:

oral – 500mg twice a day and increase by 500mg per week as needed for glycemic control.  Max 2550 mg/day

extended release tablets: 500mg daily and increase to 2000mg daily (may be divided into 1000mg 2x a day).

Common adverse reaction:

• nausea
• vomiting
• diarrhea
• flatulence
• weakness
• rash

Contraindicated with serum creatinine >1.5 mg/dL or Cr Clearance <60 mL/min.  Use caution in the elderly with normal creatinine as decreased muscle mass may decrease serum creatinineand mask renal insufficiency.  Caution is used to prevent lactic acidosis. 

Sulfonylureas

Stimulate secretion of insulin from pancreas beta cells.

Second generation

• glyburide (Diabeta®,Micronase®,Glynase®): 2.5mg 30 minutes before breakfast and increase every 2 weeks up to 20 mg
• glymepiride(Amaryl®) 1-2 mg with first meal and increase to 8mg/day titrating every 1-2 weeks.
• glypizide(Glucotrol®, Glucotrol XL®). 2.5mg 30 minutes before breakfast or dinner and increase every 2 weeks up to 40 mg. Used more often in the elderly due to shorter half life and less risk of hypoglycemia
• chlorpropramide (Diabenese) has longest half life of the list four.

Potential adverse effects: hypoglycemia, nausea, skin rash, abnormal liver enzymes.

Hypoglycemia risk may increase with concurrent use with salicylates, sulfonamides, fibric acid derivativies (e.g. gemfibrozil), and warfarin.

Hypoglycemia can be seen up to 24 hours after dose especially longer acting sulfonylureas.

Other notes: May use with insulin, glucophage, and TZD’s.  Some studies have shown worse outcome when patient with MI are taking sulfonylurea. 

 

Thiazolidinediones (TZD’s)

Benefits:

• Acts on the liver, muscle and adipose tissue to increase insulin sensitivity and decrease glucose production.  Helps the body utilize glucose from muscle and fat.
• Pioglitazone more than rosiglitazone improves panel (raises HDL , lowers triglycerides with minimal LDL elevation)
• May preserve pancreas beta cell function.
• May be used alone or with sulfonylurea, metformin,or insulin but usually not started as a monotherapy.

Risks

• Weight gain due to increase fat cells and fluid retention
• Worsening heart failure,
• Risk of MI
• Bone fractures from decrease bone mineral density
• Eczema
• Macularedema especially in those with peripheral edema.
• Liver toxicity

♦ Cardiac risk seems to be higher in rosiglitazone.

♦ There is concern about concurrent insulin and TZD’s worsening heart failure.

Rosiglitazone (Avandia®) 4mg in single or divided doses.  Increase to 8mg prn after 8-12 weeks.  With sulfonylurea limit to 4mg. 

Pioglitazone (Actos®): 15-45 mg daily.  With combo therapies, decrease sulfonylurea or insulin dose prn to avoid hypoglycemia.  Heart failure patients start at 15mg and monitor closely for 2-3 months before up titrating dose.

References:

• Uptodate 2009, Sulfonylurea use in diabetes, David McCullock MD et al.
• UptoDate 2009, Thiazolidinediones in the treatment of diabetes mellitus, David McCullock MD et. al.
• Lexi-comp