Diabetes Mellitus Management - Hypoglycemic drugs

Question 1

Insulin preparations

Answer 1

Rapid acting (1hr peak) - Lispro, Aspart, Lulisine
Short acting (2-3hr peak) - Regular
Intermediate acting (4-10hr peak) - NPH
Long acting (No real peak) - Detemir, Glargine

Question 2

Insulin mechanism of action

Answer 2

Binds to insulin receptor (tyrosine kinase activity)
Liver: High glucose stored as glycogen
Muscle: High glycogen, protein synthesis
Fat: High TG storage
Cell membrane: Increased potassium uptake

Question 3

Amylin analogs:

Pramlintide

Answer 3

MOA:
Low glucagon release
Low gastric emptying
High satiety

Adverse effects:
Hypoglycemia (in setting of mistimed prandial insulin), nausea

Question 4

GLP-1 analogs - Mechanism of action

Exenatide, Liraglutide

Answer 4

Low glucagon release
Low gastric emptying
High glucose dependent insulin release *

Question 5

GLP-1 analogs - Adverse effects

Exenatide, Liraglutide

Answer 5

Nausea, vomiting, pancreatitis
Promote weight loss (often desired) *
High satiety (often desired effect)

Question 6

Biguanides - Mechanism of action

Metformin

Answer 6

Inhibits hepatic gluconeogenesis and the action of glucagon, by inhibiting mGPD
High glycolysis (high insulin sensitivity)
Peripheral glucose uptake (high insulin sensitivity)

Question 7

Biguanides - Adverse effects

Metformin

Answer 7

GI upset, lactic acidosis (use with caution in renal insufficiency). - Check creatinine levels prior
B12 deficiency.
Promotes weight loss *

Question 8

Sulfonylureas

Answer 8

1st gen: Chlorpropamid, Tolbutamide
2nd gen: Glimepiride, Glipizide, Glyburide

Meglitinides: Nateglinide, Repaglinide

Question 9

Sulfonylureas - Mechanism of action

Answer 9

Close potassium channel in pancreatic beta cell membrane –> Cell depolarizes –> Insulin release via high Calcium influx

Insulin release independent (regardless) of glucose concentrations
Require pancreatic function (does not work in DM 1)

Question 10

Sulfonylureas - Adverse effects

Answer 10

Hypoglycemia (high risk with renal failure)
Weight gain

1st gen: Disulfiram like reactions (hangover)
2nd gen: Hypoglycemia

Question 11

DPP-4 inhibitors - Mechanism of action

Linagliptin, Saxagliptin, Sitagliptin

Answer 11

Inhibit DPP-4 enzyme that deactivates GLP-1 (hence GLP-1 is activated)
Low glucagon release
Low gastric emptying
High glucose dependent insulin release
Satiety

Question 12

DPP-4 inhibitors - Adverse effects

Linagliptin, Saxagliptin, Sitagliptin

Answer 12

Mild urinary or respiratory infections
Weight neutral

Low risk of hypoglycemia

Question 13

Glitazones/Thiazolidinediones - Mechanism of action

Pioglitazone, Rosiglitazone

Answer 13

Activate PPAR-gamma (a nuclear receptor) –> High insulin sensitivity and high levels of adiponectin –> regulation of glucose metabolism and fatty acid storage

Question 14

Glitazones/Thiazolidinediones - Adverse effects

Pioglitazone, Rosiglitazone

Answer 14

Weight gain
Edema*
HF
High risk of fractures 
Delayed onset of actions (several weeks)

Question 15

Sodium-glucose cotransporter 2 (SGLT2) inhibitors - Mechanism of action

Canaglifozin
Dapaglifozin
Empaglifozin

Answer 15

Blocks reabsorption of glucose (and Na) in proximal convoluted tubules leading to high urinary glucose loss and hence, low blood glucose levels

Effectiveness depends on GFR, measure creatinine prior to use.

Question 16

Sodium-glucose cotransporter 2 (SGLT2) inhibitors - Adverse effects

Canaglifozin
Dapaglifozin
Empaglifozin

Answer 16

Glucosuria
UTIs
Vaginal yeast infection
Hyperkalemia
Dehydration (orthostatic hypotension)
Weight loss *

Used when first line meds are not adequate

Question 17

Alpha-glucosidase inhibitors - Mechanism of action

Acarbose, Miglitol

Answer 17

Inhibit intestinal brush border alpha-glucosidases –> delayed carbohydrate hydrolysis and glucose absorption –> low postprandial hyperglycemia

Question 18

Alpha-glucosidase inhibitors - Adverse effects

Acarbose, Miglitol

Answer 18

Gi upset

Not recommended with impaired kidney function