Diabetes Drugs

Question 1

4 short acting insulins

Uses

Answer 1

Lispro, Aspart, Glulisine, Regular

Uses: bolus or mealtime

Question 2

3 intermediate / long-acting insulins

Use

Answer 2

NPH (neutral protamine hagedorn), glargine, detemir

Basal

Question 3

3 sulfonylureas
Route of delivery
Mechanism
Adverse rxns (5)

Answer 3

• Glipizide, Glyburide, Glimepiride
• Oral
• Mechanism – binds SUR1 receptor on beta cells → increased insulin secretion.
• Adverse effects – hypoglycemia, weight gain, use w/ caution in elderly / renal failure / liver failure

Question 4

2 Meglitinides
Route of delivery
Mechanism
Adverse rxns (4)

Answer 4

• Nateglinide, Repaglinide
• Oral
• Mechanism – similar to sulfonylurea, but shorter acting and less potent
• Adverse rxns – hypoglycemia (mild), weight gain (mild), use w/ caution in renal and liver failure.

Question 5

Metformin
What type of drug?
Mechanism
Advantages (2)
Disadvantages (4)
Contraindications (6)

Answer 5

• Type - Biguanide
• Mechanism – Not well understood. Increases insulin sensitivity (esp at liver) and / or decreases hepatic glucose production.
• Advantages – weight loss, no hypoglycemia b/c it doesn’t increase insulin secretion
• Disadvantages – GI sxs (metallic taste, nausea, diarrhea), and lactic acidosis (rare)
• Contraindications (all risk factors for lactic acidosis) – renal insufficiency (Cr > 1.5 mg/kg), liver disease, alcohol abuse, heart failure, serious acute illness, >80 y/o

Question 6

2 Thiazolidinediones
Mechanism (3)
Timing
Advantages (2)
Disadvantages (3) 
Contraindications (2)

Answer 6

• Pioglitazone, Rosiglitazone
• Mechanism
• Agonist of peroxisome proliferator activated receptor gamma (PPAR-gamma), nuclear receptor superfamily
• Sensitizes skeletal muscle to insulin → increased glucose uptake
• Decreases hepatic GNG
• Delayed onset, taking 6-12 weeks for effect
• Advantages – no hypoglycemia b/c it doesn’t stimulate release. Pioglitazone improves lipid profile.
• Disadvantages – weight gain, edema / fluid retention, risk of fractures
• Contraindicated in heart / liver failure, increased risk of MI / stroke. Not used much any more due to these reasons.

Question 7

Acarbose
Type of drug
Mechanism
Adverse rxns (2)

Answer 7

• Alpha-Glucosidase Inhibitor
• Mechanism – Inhibits alpha-glucosidase in intestinal wall → delayed digestion / absorption of carbs and conversion to glucose
• Adverse rxns – GI (flatulence, diarrhea). Rarely used.

Question 8

2 Incretin mimetics
Route of delivery
Mechanism (3)
Advantages
Disadvantages (2)

Answer 8

• Exenatide, Liraglutide
• Injected SQ
• Mechanism
• Agonist at GLP-1 receptor. Promotes glucose-mediated insulin secretion.
• Decreases hepatic glucose production
• Slows gastric emptying
• Advantages – reduces appetite and improves satiety (due to slowed gastric emptying) → weight loss. May support beta cell mass / survival.
• Disadvantages – GI (nausea, vomiting), low risk of hypoglycemia so use w/ caution in renal insufficiency

Question 9

2 DPP-4 inhibitors
What is DPP-4?
Mechanism
Adverse rxns

Answer 9

• Sitagliptin, Saxagliptin
• DPP4 = dipeptidyl peptidase 4, which degrades GLP-1
• Mechanism – increases endogenous GLP-1 and insulin secretion
• NO major side effects

Question 10

3 SGLT2 inhibitors
Mechanism
Advantages (3)
Disadvantages (3)
Contraindication

Answer 10

• Canagliflozin, Dapagliflozin, Empagliflozin
• Mechanism – Inhibition → increased urinary glucose excretion
• Advantages – weight loss, decreases systolic BP (due to acting as osmotic diuretic), risk of hypoglycemia is lower than others
• Disadvantages – Genital / urinary tract infections (esp vulvovaginal candidiasis; due to higher glucose in urine), renal insufficiency, orthostatic hypotension,
• Contraindicated if GFR less than 45 or w/ severe liver impairment

Question 11

Glucagon
Mechanism
Adverse rxn

Answer 11

• Mechanism – stimulates adenylate cyclase to increase cAMP → hepatic GNG + glycogenolysis → increased BG
• Adverse rxn – minor nausea

Question 12

Treating type 2
What is first?
When should more drugs be added?
Insulin strategies

Answer 12

• Lifestyle changes
• Metformin is used first. Sulfonylurea if there is a contraindication to metformin.
• A1c should be monitored every 3 months. If >7% after 3 months, add 2nd drug. If still not corrected after another 3 months, add 3rd drug or substitute the 2nd drug for basal + bolus insulin.
• Insulin – Start basal insulin at night time. Adjust dose to target fasting morning BG 80-130. If BG is high at meals or bedtime, add NPH in morning or start mealtime insulin (based on carb content of meal).

Question 13

2 main types of insulin regimens

Answer 13

• NPH once in morning and once at night + regular insulin at breakfast and supper.
• No regular insulin at lunch b/c NPH peaks at lunch time.
• Must tailor meals to insulin
• Intensive insulin regimen: Glargine (once a day at any time, no peak) + aspart or lispro after meals.
• Should tailor insulin to carbs. More flexible. Use ICR.