MedSurg 3 - Drugs for Diabetes mellitus

Question 1

SULFONYLUREAS

Glimepiride (Amaryl®)
Glipizide (Glucotrol®, Glucotrol XL®)
Glyburide (Diabeta®, Micronase®)

*** All sulfonylureas are associated with WEIGHT GAIN – not best choice for obese patients.

Answer 1

Sulfonylureas called insulin secretagogues.

MOA:

• • they work by stimulating the production and release of insulin by the pancreatic beta cells;
• • decreases glycogenolysis & gluconeogenesis;
• • enhance cellular sensitivity to insulin
• Give before breakfast
• Side Effects:
• Hypoglycemia, diarrhea, HA, nausea or vomiting, skin rash, increased SENSITIVITY TO SUNLIGHT, intolerance to alcohol, WEIGHT GAIN.

Question 2

MEGLITINIDES

Repaglinide (Prandin®)
Nateglinide (Starlix)

*** Mimics normal blood glucose response to eating.

Answer 2

MOA:

• • Meglitinides work by stimulating insulin release from the pancreas beta cells. Mediated through a different binding site than the sulfonylureas;
• • short onset of action & short half-life.
• • Insulin release diminishes at low glucose concentrations. – Lowers post-meal blood sugars (post-prandial blood glucose).
• Prandin and Starlix should be taken 0-30 minutes before meal. If a meal is missed, dose should be skipped for that meal.
• Side effects:
• Hypoglycemia, headache, paresthesias, angina, sinusitis, GI disturbances, UTI, joint pain.

Question 3

BIGUANIDE

Metformin (Glucophage®)

*** First-line therapy in obese patients with type 2 diabetes mellitus (does not promote weight gain)

*** Also Used in Pre-diabetes to prevent DM especially in obese & those with genetic predisposition.

Answer 3

MOA:

• • Glucophage increases the effect of insulin that is already present in the bloodstream by enhancing insulin sensitivity in hepatic and peripheral tissues;
• • reduces hepatic glucose output; &
• • improves glucose transport into the cells.
• Glucophage should be taken with meals. It is usually given 2-3 times a day.
• Side effects:
• Diarrhea, stomach discomfort (usually decreases over time). Monitor serum creatinine and BUN levels prior to therapy and periodically. Monitor liver function periodically.

Question 4

Alpha (α) Glucosidase Inhibitors

Acarbose (Precose®)
Miglitol (Glyset®)

*** Not recommended for patients with inflammatory bowel disease or history of bowel obstruction.

Answer 4

MOA:
– work by slowing the digestion of CHOs, thus slowing the absorption of glucose from GI tract. Called “Starch blockers.” This helps reduce the peaks in blood glucose. Remember: Limit CHO digestion.

• Taken 15 minutes before each meal (or with first bite of each main meal). taken up to 3 times a day.
• Side effects:
• Flatulence, diarrhea, abdominal pain (usually diminishes over 4-8 weeks). Not recommended for patients with inflammatory bowel disease or history of bowel obstruction.

***Effectiveness measured by checking 2 hour postprandial glucose levels.

Question 5

Thiazolidinediones “glitazones”

Rosiglitazone (Avandia®)
Pioglitazone (Actos®)

** ⊗ Avandia now used with caution!!! FDA Safety Alert!!! Black Box Warning!!! **

Answer 5

MOA:

• • These drugs increase the effect on insulin that is already present in the bloodstream by sensitizing resistant cells to insulin.
• • Enhances insulin sensitivity in both muscle and adipose tissue;
• • inhibits hepatic glucose production. No effect on insulin secretion.
• • Remember: increase insulin receptor site sensitivity.
• Avandia and Actos taken as a single daily dose (with or without meals)
• Side effects: ↑ in total and LDL cholesterol, ↓ Hg & Hct (anemia), headache, water retention (edema). Monitor liver function tests before drug is started, then every other month thereafter.
• **Especially useful in obese patients.
• **Not recommended for patients with heart failure (water retention)
• **Does not cause hypoglycemia when used alone because it does not ↑ insulin production

Question 6

Dipeptidyl Peptidase-4 (DDP-4) Inhibitors – Newest Class

sitaglyptin (Januvia®)
vildagliptin (Galvus®)
saxagliptin (Onglyza®)

☞Januvia has new FDA warning – increased risk for pancreatitis; pancreatic cancer!!!

Answer 6

MOA:
– Enhances the action of incretins, naturally occurring hormones that ↑ insulin secretion in presence of ↑ BG; given orally; are glucose dependent – respond to ↑ BG & result in insulin release only when needed.

• Given without regard to meals; once daily
• Side effects:
• hypoglycemia in combination with metformin or thiazolidinedione. Runny/stuffy nose, headache, N, D,
• • Used for managing Type 2 DM who do NOT take insulin
• • Used as adjunct to diet and exercise for Type 2 DM to improve glycemic control
• • Absence of weight gain – so good choice for obese patients
• • Concurrent use of Januvia with digoxin (Lanoxin) slightly increases digoxin levels

Question 7

Summary of How Oral Hypoglycemic Agents Work

Answer 7

Increases Cell’s Sensitivity to Insulin:
Biguanide - metformin (Glucophage)
Thiazolidinediones - pioglitazone (Actos); rosiglitizone (Avandia)(FDA Safety Alert)

Increases Production and Release of Insulin:
Sulfonylureas (ex: glyburide (Micronase), glipizide (Glucotrol), glimepiride (Amaryl)
Meglitinides [repaglinide (Prandin) or nateglinide (Starlix)]

Slows/Limits Digestion and Absorption of Carbohydrates:
Alpha-glucosidase inhibitors: acarbose (Precose); miglitol (Glyset)

Enhance Action of Incretins - Increase production of insulin in presence of high blood glucose:
Dipeptidyl Peptidase-4 (DDP-4) Inhibitors – Newest Class
sitaglyptin (Januvia®) [FDA warning]
vildagliptin (Galvus®)