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Introduction
History
Physical Exam
Laboratory Tests
Counseling
Drug Therapy
Overview
Oral Agents
Insulin
Misc. Drugs
Immunizations
Referrals

Keep in mind that at each appointment, the following should occur:

1. Review/update current medications and doses
2. Daily aspirin therapy (75-325mg) should be considered in men age 50+ and women age 60+ with one additional major cardiovascular disease risk factor.
3. Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) should be prescribed in anyone with a history of elevated urine albumin/creatinine ratio (>30), history of hypertenion, heart failure, or known vascular disease
4. Statins should be considered in any person with diabetes over the age of 40 with another major cardiovascular disease risk factor to prevent vascular disease independent of and in addition to its cholesterol lowering effects.

Non-insulin Diabetic Medications

The six classes of medications in this category include:  sulfonylureas, meglitinides, thiazolidinediones, biguanides, alpha-glucosidase inhibitors, and agents that increase GLP-1.  These classes can be grouped together based on their mechanism of action. (NOTE: Drugs on the SHARING formulary are indicated in red; see formulary for specific details.)

• Drugs that stimulate the pancreas to produce more insulin: sulfonylureas, meglitinides, and agents that increase available GLP-1. 
• Drugs that sensitize the body to insulin or control hepatic glucose production: thiazolidinediones, biguanides, and agents that increase available GLP-1.
• Drugs that slow the absorption of starches:  alpha-glucosidase inhibitors, and agents that increase available GLP-1.

Sulfonylureas

• Mechanism of Action:  stimulates postprandial insulin secretion from pancreatic b-cells.
• Major Side Effects:  **hypoglycemia**, may be greater with liver and kidney disease.
• Common Medications:  glipizide or glipizide-ER (Glucotrol® or Glucotrol XL®), glyburide (Micronase®, Glynase®, or DiaBeta®), & glimepiride (Amaryl ®). Note that glipizide is available as a generic extended release medication which may improve compliance as it can be given once daily. Glimeperide can also be given once daily for full effect. All other medications must be split into BID dosing if giving more than half maximal dose.

Meglitinides

• Mechanism of Action:  stimulates insulin release from pancreatic b-cells very rapidly and for a short duration (has to be taken directly before meals) but flexible in case of changing or intermittent meal schedules.
• Major Side Effects:  **hypoglycemia**, but less than with sulfonylureas because of shorter duration.
• Common Medications:  repaglinide (Prandin®) & nateglinide (Starlix®); note that nateglinide is the least potent of all oral agents with respect to its impact on A1C.

Thiazolidinediones (a.k.a “glitazones” or “TZDs”)

• Mechanism of Action:  decrease insulin resistance by making target tissues (e.g., adipose cells) more sensitive to insulin.  It also suppresses gluconeogenesis in the liver.
• Major Side Effects: weight gain, edema, exacerbation of heart failure (do not use with Class III or IV heart failure); liver function abnormalities are rare (<0.2%)
• Common Medications:  pioglitazone (Actos ®) & rosiglitazone (Avandia ®)

Biguanides

• Mechanism of Action:  decreases hepatic gluconeogenesis and sensitizes skeletal muscle to insulin which promotes glucose uptake.
• Major Side Effects: diarrhea and abdominal discomfort, can prevent lactate clearance so not recommended for those at increased risk of lactate production (e.g., renal insufficiency with serum creatinine >1.4 mg/dL in females and >1.5 mg/dL in males, liver disease, heart failure, hospitalized patient, on the day and two days after a planned contrast procedure which can lead to higher risk of acute renal failure in diabetic patients)
• Common Medications:  metformin and metformin-ER (Glucophage®, Glucophage-XR®)

Alpha-Glucosidase Inhibitors

• Mechanism of Action:  competitively inhibits monosaccharide and oligosaccharide hydrolysis in the small intestine to decrease carbohydrate absorption.
• Major Side Effects:  abdominal discomfort & flatulence
• Contraindications:  may worsen symptoms of inflammatory bowel disease
• Common Medications:  acarbose (Precose®) & miglitol (Glyset®)

Glucagon Like Peptide-1 (GLP-1) agonists and Dipeptidyl peptidase (DPP) inhibitors that increase endogenous GLP-1 levels by inhibiting its metabolism

• Mechanism of Action: enhances glucose-stimulated insulin secretion from islets and possibly enhances islet longevity, inhibits hepatic gluconeogenesis, slow intestinal transit time reducing immediate postprandial hyperglycemia and enhancing postprandial satiety and weight loss (more likely to occur with Byetta).
• Major Side Effects: hypoglycemia if combined with other agents that stimulate insulin release such as sulfonylureas so sulfonylureas should be reduced by 50% at time of onset; nausea with Byetta only
• Contraindications:  known gastroparesis or decreased intestinal transit time

Other Medications: 

• GLP-1 agonist: exenatide Byetta® available as a twice daily injection to be given before breakfast and supper
• DPP-IV inhibitors: sitagliptin (Januvia®), and vildagliptin