Diabetes Mellitus 2

Question 1

Glyburide (Sulfonylureas)

Answer 1

MOA: K+ ATP channels close, depolarization prolonged, Ca2+ influx, insulin containing vesicles exocytosis,

can cause hypoglycemia

Question 2

Repaglinide (Meglitinides)

Answer 2

MOA: K+ ATP channels close, depolarization prolonged, Ca2+ influx, insulin containing vesicles exocytosis

Can cause hypoglycemia

Fast acting, post prandial due to rapid absorption

Question 3

Metformin (Biguanide)

Answer 3

MOA: impairs mitochondrial respiration, AMP accumulation, AMP kinase activation, change in gene expression
-> increases insulin sensitivity, glucose uptake, FA uptake and oxidation
-> decreases intestinal glucose absorption, hepatic glucose

DRUG of CHOICE, does not cause hypoglycemia, promotes weight loss

excreted unchanged in urine

Question 4

Rosiglitazone (Thiazolidinediones)

Answer 4

MOA: binds to PPARy (nuclear receptor), drug-receptor complex migrates to DNA causing activation of gene transcription involved in glucose and FA metabolism
-> increases GLUT4 expression (increased insulin sensitivity)
-> reduces FFA

used in highly resistant DM2 patients

Question 5

Acarbose

Answer 5

MOA: competitively binds to a-glucosidases on intestinal membrane, prevents glucose absorption

-> doesn’t help with diabetic state, prevents hyperglycemia after meals, needs to be taken with other anti-diabetic drug

Question 6

Dapagliflozin

Answer 6

MOA: SGLTi (sodium-glucose transporter inhibitors) mostly at proximal tubule
–> glucose excretion through urine
–> water excretion increased due to osmosis (decreases bp)

can cause UTI

Question 7

Sitagliptin

Answer 7

MOA: DPP-4 inhibitor, allows GLP-1 to remain active for longer
–> reduces glucagon secretion (decreased glucose in blood)
–> suppresses appetite
–> slows gastric emptying
–> stimulates insulin secretion

insulin secretion only when glucose is increased

Question 8

Exenatide

Answer 8

MOA: agonist of GLP-1 receptors, incretin mimetic (causes insulin secretion only when glucose is increased e.g. post prandial)

Question 9

Pramlintide

Answer 9

MOA: amylin mimetic
–> improves satiety
–> delays gastric emptying
–> decrease glucagon secretion postprandial