Insulin and Oral Hypoglycemic Drugs

Question 1

Forms of Diabetes

Answer 1

Type 1: Insulin dependent loss of Beta cells
Type 2: Insulin independent decreased response to insulin in tissues
Type 3: Specific causes such as gene mutations (glucokinase or insulin gene)
Type 4: Gestational Diabetes (4% of US pregnancies)

Question 2

Insulin Peparations

Answer 2

Rapid acting:
Inhaled powder: Peak in 30min-2hours
Injected form: zinc containing solution: Peak in 30min-2hours
Short-acting: zinc containing
Intermediate Acting:
Lent or Neutral, protamine, and Hagedorn (NPH)
Peak 2 hrs and duration 24 hours
Long-acting:
Insulin glargine or determir
Peak 4 hours duration 36 hours

Question 3

Tolbutamide (Orinase)

Answer 3

First generation Sulfonylurea
Lasts 8 hours
Causes beta cell depolarization and insulin release due to an action of ATP-dependent potassium channels
Increases insulin action at target tissues
Reduces serum glucagon levels

Question 4

Glyburide (Diabeta, Micronase)

Answer 4

Second Generation Sulfonylurea
Lasts 12-24 hours
Causes beta cell depolarization and insulin release due to an action of ATP-dependent potassium channels
Increases insulin action at target tissues
Reduces serum glucagon levels
100x more potent than 1st generation
Less frequent hypoglycemia than 1st

Question 5

Sulfanylureas

Answer 5

Side effects:
hypoglycemia, weight gain, skin rash, elevated liver enzymes, allergic reactions
Contraindications:
Pregnancy (potentially teratogenic)
History of adverse reactions to sulfa drugs
Ineffective in major stress (surgery, severe infection, trauma)

Question 6

Meglitinides
Repaglinide (Prandin)
Nateglinide (Starlix)

Answer 6

Insulin release via inhibition of ATP dependent potassium current. Acts at a site distinct from sulfonylurea site
Rapid onset (20 minutes) and short duration (3 hours)
Ideally suited for preventing high glucose after eating.
Less likely to cause hypoglycemia, due to short duration
Can cause diarrhea, allergic/dermatological problems, and headache.

Question 7

Metformin (Glucophage)

Answer 7

Biguanide
Inhibits glucose production by the liver
Increases tissue sensitivity to insulin
Decreases GI glucose absorption
Inhibits genes for gluconeogenisis in liver
Comparable efficacy to sulfas
Used in combination with insulin secreting drugs, insulin sensitizing drugs, or insulin.
Little protein binding
Can cause metallic taste, nausea and diarrhea, reduce absorption of vitamin B12 and folic acid
Does not cause hypoglycemia and does not increase body weight

Question 8

Acarbose (Precose)

Answer 8

alpha-Glucosidase inhibitor
Competitive inhibition of intestinal a-glucosidase, which breaks down starch
Delays carbohydrate absorption
Causes bloating and flatulence (70%)
Contraindicated in intestinal diseases that can be exacerbated by gas
Can exacerbate hypoglycemia when used in combination with insulin
Need to use glucose to reverse, not starch or sucrose

Question 9

Thiazolidinediones
Rosiglitazone (Avandia)
Pioglitazone (Actos)

Answer 9

Agonist for nuclear receptor peroxisome profilator activated receptor gamma (PPAR-gamma)
Activates gene transcription in adipocytes and liver
Enhances insulin sensitivity in muscle, liver, and adipose tissues; enhances insulin action on glucose and lipid metabolism.
Requires 3-6 weeks for maximum effect
Monotherapy for type 2 diabetes, ineffective alone for type 1
Decreases HgbA1C 1-1.5%
Causes weight gain, fluid retention
Contraindicated in heart failure or liver disease
Rosiglitazone found 43% increase MI so pioglitazone typically preferred

Question 10

Sitagliptin (Merck)

Answer 10

Inhibition of dipeptidyl-peptidase 4 (DPP4)
DPP4 breaks down molecule that signals insulin release and decreased glucagon
Half-life 11.8-14.4 hours
Monotherapy - less effective than metformin or suflas
Combination - use with metformin, pioglitazone, or rosiglitazone
Well tolerated, no weight gain or hypoglycemia

Question 11

Exenatide

Answer 11

Incretin mimetic
Enhances glucose dependent insulin secretion
Suppresses inappropriately elevated glucagon
Slows gastric emptying, reducing glucose absorption
Subcutaneous injection
Not used as monotherapy
Can cause indigestion or diarrhea
Decrease HbA1c by 0.4-0.8%
Weight loss of 1-3kg depending on combination used

Question 12

Pramlintide

Answer 12

Synthetic analog of human amylin
Amylin slows gastric emptying, suppresses glucagon secretion, and regulates appetite
Type 1 and 2 patients taking mealtime insuiln can take this
SQ before meal
Decreases required insulin
Decreases weigh 1.5kg
Decreases HbA1c 0.5%