Diabetes oral treatment

Question 1

· List six classes of non-insulin medications used to normalize blood glucose in diabetes and explain their mechanisms of action

Answer 1

Sulfonylureas (insulin secretagogues), amylin analog, incretin enhancer (GLP-1 agonists and DPP-4 inhibitors), thiazolidinediones, metformin, and sodium-glucose co-transporter inhibitor

Question 2

sulfonylureas MOA

Answer 2

increases pancreatic beta cell insulin secretion. Closes ATP-sensitive K channels in beta cells > depolarization> opening of voltage-gated calcium channels > influx of calcium into the β-cell > fusion of insulin-containing secretory granules with the cell membrane > insulin secretion.

Question 3

list sulfonylureas

Answer 3

glipizide (Glucotrol), glyburide (Diabeta, Micronase), and glimepiride (Amaryl).

Question 4

sulfonylureas pros and cons

Answer 4

pros: inexpensive, combo pills with metformin and thiazolidinediones. Cons: weight gain, hypoglycermia, loses effectiveness with longer duration of diabetes

Question 5

sulfonylureas excretion

Answer 5

metabolized by liver, excreted renally- use with caution in renal or liver dz

Question 6

sulfonylureas side effects

Answer 6

sulfa allergy, hemolytic anemia in individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency

Question 7

list biguanides

Answer 7

metformin (glucophage)

Question 8

metformin MOA

Answer 8

Potentiates the suppressive effect of insulin on hepatic glucose production (decreases blood glucose). Does NOT stimulate insulin secretion OR increase circulating insulin levels

Question 9

metformin pros

Answer 9

no hypoglycemia, inexpensive, no weight gain, combo pill with sulfonylureas, thiazolidinediones and DPP-4 inhibitors

Question 10

metformin cons

Answer 10

side effects include nausea, bloating, diarrhea and risk of lactic acidosis with contrast media CHF, renal insufficiency, and liver dz

Question 11

Thiazolidinediones MOA

Answer 11

Increase insulin sensitivity by binding nuclear peroxisome proliferator-activated receptors (PPAR)-amma. Stimulates adiponectin (hormone from adipose tissue) production and action

Question 12

list examples of thiazolidinediones

Answer 12

rosiglitazone (Avandia) and pioglitazone (Actos),

Question 13

Thiazolidinediones pros and cons

Answer 13

pros: MOA, other beneficial effects. Cons: worsening of CHF, expensive, risk of bladder cancer with >1 year of use, not used in liver dz

Question 14

what is the incretin effect

Answer 14

Giving an oral glucose load leads to more insulin secretion (2-3 fold) than giving an isoglycemic IV glucose infusion due to incretins in the gut which augment insulin secretion only if blood glucose is elevated. This is reduced in type 2 diabetes

Question 15

List incretins

Answer 15

glucagon-like peptide-1 (GLP-1 produced in distal ileum and colon) and glucose-dependent insulinotropic polypeptide (GIP)

Question 16

How does GLP-1 lower glucose

Answer 16

food stimulates release of GLP-1 which 1. stimulates glucose dependent insulin secretion > decreases hepatic glucose output. 2. suppresses postprandial glucagon secretion > decreases hepatic glucose output. 3. slows gastric emptying. 4. Inhibits food intake

Question 17

Why is GLP-1 not useful med

Answer 17

Native GLP-1 peptide is rapidly cleaved and inactivated by dipeptidyl peptidase IV (DPP-4) within minutes of appearing in the circulation

Question 18

List GLP-1 agonists

Answer 18

exenatide (Byetta), liraglutide (Victoza), exenatide Qwk (Bydureon), albiglutide (Tanzeum), dulaglutide (Trulicity)

Question 19

pros and cons of GLP-1 agonists

Answer 19

pros: multiple mechanisms to lower postprandial glucose, effects are glucose dependent and weight loss. Cons: SC injections, side effects (medullary thyroid carcinoma), expensive

Question 20

DPP-4 inhibitors MOA

Answer 20

Inhibit DPP-4 which breaks down GLP-1

Question 21

List DPP-4 inhibitors

Answer 21

sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), and alogliptin (Nesina).

Question 22

DPP-4 inhibitors pros and cons

Answer 22

pros: multiple MOA to lower postprandial glucose, oral, once daily, weight neutral, combo pill with metformin. Cons: less potent effects, expensive, side effects (nasopharyngitis, stevens johnson syndrome, acute pancreatitis)

Question 23

Amylin function

Answer 23

hormone secreted by beta cells with diurnal pattern like insulin. Suppresses postprandial glucagon, slows gastric emptying and decreases food intake

Question 24

Amylin levels in diabetes

Answer 24

T1D: absolute deficiency. T2D: initially elevated, then levels parallel the decline in insulin secretion

Question 25

list amylin analogues

Answer 25

Pramlintide (Symlin)

Question 26

amylin analog pros and cons

Answer 26

pros: multiple MOA, induces weight loss. Cons: SC injection (up to 7 a day), side effects, expensive, cant be injcted with insulin

Question 27

Sodium-glucose co-transporter inhibitors MOA

Answer 27

inhbits reabsorption of glucose in kidneys , thus incrasing glucose excretion and reducing circulating glucose levels

Question 28

List Sodium-glucose co-transporter inhibitors

Answer 28

canagliflozin (Invokana), dapagliflozin (Farxiga)

Question 29

Sodium-glucose co-transporter inhibitors pros and cons

Answer 29

pros: novel mechanism, weight loss pill. Cons: increasd risk for UTI and GU infections, increased risk for hypokalemia, expensive, long term safety unknown

Question 30

legacy effect

Answer 30

patients on intensive control continued to have reduced risk for complications compared with the group receiving conventional control, even after the treatment phase of the trials ended and their mean A1c levels increased.

Question 31

Diabetic treatment goals

Answer 31

A1C<180mg/dl

Question 32

compare cost of glucose lowering meds

Answer 32

sulfonylureas and metformin are 4$/month, exenatide is 600$/month. Insulin is 100$/ 1000 units