Diabetes Part 2

Question 1

What is the target organ for sulfonylureas (SU)?

Answer 1

pancreas

Question 2

What is the target organ for glinides?

Answer 2

pancreas

Question 3

What are the target organs for biguanide (metformin)? (3)

Answer 3

liver, muscle, adipose tissue

Question 4

What are the target organs for thiazolidinediones (TZD)? (3)

Answer 4

adipose tissue, muscle, liver

Question 5

What is the target organ for alpha-glucosidase inhibitors (AGI)?

Answer 5

GIT (s. intestine)

Question 6

What is the target organ for DPP-4 inhibitors?

Answer 6

GIT

Question 7

What is the target organ for SGLT-2 inhibitors?

Answer 7

kidneys

Question 8

What is the target organ for insulin?

Answer 8

liver

Question 9

What are the target organs for GLP-1 receptor agonists? (4)

Answer 9

GIT, brain, liver, pancreas (beta cells)

Question 10

What are the target organs for amylin analogue (pramlintide)? (3)

Answer 10

GIT, liver, brain

Question 11

What is the MOA of sulfonylureas (SU)?

Answer 11

Enhance insulin secretion from beta cell (independent of glucose load)

Question 12

What is the MOA of glinides?

Answer 12

Enhance insulin secretion from beta cell (independent of glucose load)

Question 13

What is the MOA of biguanide (metformin)?

Answer 13

Decrease hepatic glucose production and increase insulin sensitivity

Question 14

What is the MOA of TZDs?

Answer 14

Activate PPAR-gamma in muscle, liver, and fat leading to changes in gene transcription; inc glucose transporter expression

Question 15

What is the MOA of AGIs?

Answer 15

Inhibit enzymes in the small intestine that hydrolyze polysaccharides into simple sugars→ delays absorption of dietary CHO

Question 16

What is the MOA of DPP-4 inhibitors?

Answer 16

Inhibits enzyme responsible for the breakdown of endogenous GLP-1

Question 17

What is the MOA of SGLT-2 inhibitors?

Answer 17

Inhibits the SGLT-2 transporter in the kidney to dec reabsorption of glucose→ inc urinary glucose excretion

Question 18

What is the MOA of GLP-1 receptor agonists?

Answer 18

Enhances glucose dependent insulin secretion, slows gastric emptying, inc satiety, suppresses postprandial glucagon release, suppresses hepatic glucose production

Question 19

What is the MOA of amylin analogue (pramlintide)?

Answer 19

Slows gastric emptying, inc satiety, suppresses postprandial glucagon release, suppresses hepatic glucose production

Question 20

What are some clinical pearls of metformin? (7)

Answer 20

1) Cornerstone of T2DM tx- safe, effective, cheap, may reduce risk of CV and death
2) Low risk of hypoglycemia
3) Max therapeutic effect w/in 2 weeks
4) Effects FPG and PPG
5) Can cause Vit B12 deficiency in high doses w/long term use-monitor levels
6) Weight loss or neutral
7) Bad GI effects-diarrhea

Question 21

What is the initial dose when starting on metformin?

Answer 21

500 mg daily

Question 22

How is metformin titrated over 4 weeks, leading to the max clinical dose?

Answer 22

Week 1: 500 mg daily
Week 2: 500 mg BID
Week 3: 500 mg in AM, 1000 mg in PM
Week 4: 1000 mg BID→ max clinical dose

Question 23

What formulation of metformin minimizes GI effects?

Answer 23

ER formulation

Question 24

What are some clinical pearls of Sulfonylureas (SU)? (6)

Answer 24

1) Requires functioning beta-cells
2) Primarily affects FPG
3) Max therapeutic effects at 50% MDD
4) Avoid glyburide: long acting, high risk of hypoglycemia, long half life and active metabolite
5) HIGH risk of hypoglycemia
6) Limited durability: usually good for 6 months w/high secondary failure after

Question 25

What are the 3 SU drugs?

Answer 25

1) Glyburide 2) Glipizide 3) Glimeperide

Question 26

What are the 2 glinide drugs?

Answer 26

1) Repalinide | 2) Nateglinide

Question 27

What are some clinical pearls of glinides? (4)

Answer 27

1) Requires functioning beta-cells 2) Effects PPG 3) Requires multiple doses daily (before meals) 4) Less risk of hypoglycemia vs. SUs b/c rapid onset and short duration of action

Question 28

What are the 2 TZD drugs?

Answer 28

1) pioglitazone | 2) rosiglitazone

Question 29

What are some clinical pearls of TXDs? (5)

Answer 29

1) Insulin sensitizers 2) Primarily affects FPG 3) Max therapeutic effects seen at 8-12 weeks-titrating to max dose not recommended 4) Low hypoglycemia risk 5) Good A1c durability

Question 30

What are 5 SEs of pioglitazone?

Answer 30

1) edema 2) weight gain 3) atypical bone fractures 4) bladder cancer 5) macula edema

Question 31

What are 2 alpha-glucosidase inhibitors (AGIs)?

Answer 31

1) acarbose | 2) miglitol

Question 32

What are some clinical pearls of AGIs? (5)

Answer 32

1) Affects PPG 2) Most effective if diet contains large amounts of carbs 3) Requires multiple daily doses-must be present in gut to work 4) Max therapeutic effects 1 hr after eating 5) Titrate over 4-8 weeks to minimize GI SEs (abd pain, flatulence, bloating)→ poor tolerability, not used often

Question 33

What are 4 DPP-4 inhibitors?

Answer 33

1) lingagliptin 2) alogliptin 3) sitagliptin 4) saxagliptin

Question 34

What are some clinical pearls of DPP-4 inhibitors? (7)

Answer 34

1) Primarily PPG 2) Modestly effective at lowering A1c 3) Max therapeutic effect in 2 weeks 4) Weight neutral 5) Well tolerated (SEs: HA, rash, nasopharyngitis) 6) Low hypoglycemia risk 7) May need to reduce dose of SU if given in combo

Question 35

What are 3 SGLT-2 inhibitors?

Answer 35

1) canagliflozin 2) empagliflozin 3) dapagliflozin

Question 36

What are 4 benefits of SGLT-2 inhibitors?

Answer 36

1) useful for all durations of diabetes: not dependent on beta cell for efficacy; primarily affects FPG 2) weight loss 3) low risk of hypoglycemia 4) CV data

Question 37

What are 3 safety concerns of SGLT-2 inhibitors?

Answer 37

1) inc incidence of UTIs and genital infections 2) dec BP 3) acute kidney injury

Question 38

What are 5 GLP-1 receptor agonists?

Answer 38

1) exenatide 2) liraglutide 3) albiglutide 4) dulaglutide 5) lixisenatide

Question 39

What are some clinical pearls of GLP-1 receptor agonists? (7)

Answer 39

1) Work on multiple pathophys targets 2) Inc insulin secretion from beta cells-glucose dependent 3) May preserve beta-cell function and mass 4) Effects FPG and PPG 5) Weight loss of 2-4 kg over 12 weeks 6) Low hypoglycemia risk 7) Most approved to be used w/basal insulin-no FDA approval for prandial insulin

Question 40

Which 3 GLP-1 agonists are daily?

Answer 40

1) exenatide (BID) 2) liraglutide 3) lixisenatide

Question 41

What 2 GLP-1 agonists are short acting?

Answer 41

1) exenatide (BID) | 2) lixisenatide

Question 42

Which 3 GLP-1 agonists are weekly?

Answer 42

1) exenatide ER 2) dulaglutide 3) albiglutide

Question 43

Which 4 GLP-1 agonists are long acting?

Answer 43

1) exenatide ER 2) dulaglutide 3) albiglutide 4) liraglutide

Question 44

Which 2 GLP-1 agonists primarily cover PPG?

Answer 44

1) Exenatide (BID) | 2) lixisenatide

Question 45

Which 4 GLP-1 agonists primarily cover FPG?

Answer 45

1) exenatide ER 2) dulaglutide 3) albiglutide 4) liraglutide

Question 46

What is the name of the amylin analogue?

Answer 46

pramlintide

Question 47

What are some clinical pearls of amylin analogue? (6)

Answer 47

1) Effects PPG 2) Slows gastric emptying, inc hunger, thirst 3) Must be used w/intensive insulin regimens (basal-bolus) → given w/mealtime insulin-must reduce dose of bolus insulin by 50% to avoid hypoglycemia 4) Works to complement the action of insulin 5) Requires multiple daily doses 6) SEs: N/V, anorexia, inc risk of insulin-induced hypoglycemia

Question 48

What are 5 drugs that affect FPG?

Answer 48

1) Metformin 2) SUs 3) TZDs 4) SGLT-2 inhibitors 5) GLP-1 receptor agonists

Question 49

What are 6 drugs that affect PPG?

Answer 49

1) Metformin 2) Glinides 3) AGIs 4) DPP-4 inhibitors 5) GLP-1 receptor agonists 6) Amylin analog

Question 50

What are 2 combinations to avoid when using combination therapy?

Answer 50

1) SU + glinides→ same MOA w/inc risk of hypoglycemia + beta-cell burnout 2) GLP-1 + DPP-4 inhibitor→ GLP-1 agonist does what DPP-4 inhibitors do + more and is more efficacious

Question 51

What 3 drugs are safe to use in pts with CV disease?

Answer 51

1) liraglutide 2) empagliflozin 3) metformin (obese pts)

Question 52

What 4 drugs/drug classes should be avoided in CV disease pts?

Answer 52

1) saxagliptin 2) alogliptin 3) TZDs 4) SUs

Question 53

Which 5 drugs/drug classes need to be avoided or dose reduced in renal disease?

Answer 53

1) metformin 2) SUs 3) DPP-4 inhibitors (except linagliptin) 4) exenatide (ER) 5) SGLT-2 inhibitors

Question 54

At what eGFR level is metformin C/I?

Answer 54

CrCl <30

Question 55

At what eGFR level is metformin not supposed to be initiated?

Answer 55

CrCl >/=30-45

Question 56

If eGFR 45-59, what do you do with the Canagliflozin dose? If <45?

Answer 56

Give 100 mg daily; if <45→ avoid

Question 57

At what eGFR level empagliflozin to be avoided?

Answer 57

<45

Question 58

At what eGFR level dapagliflozin to be avoided?

Answer 58

<60

Question 59

What are 4 drug classes that are at highest risk of hypoglycemia when used as monotherapy and what is the strategy to lessen the risk for each?

Answer 59

- Insulin: strategy→ use rapid, long acting, and ultra-long acting - SUs: strategy→ take w/food - Glinides: strategy→ take w/food - Amylin analog: strategy→ reduce dose of bolus insulin by 50%

Question 60

Which 3 medication classes cause weight loss?

Answer 60

1) GLP-1 agonists 2) amylin analogue 3) SGLT-2 inhibitors

Question 61

Which 3 medication classes are weight neutral?

Answer 61

1) metformin 2) DPP-4 inhib 3) AGIs

Question 62

Which 4 medication classes cause weight gain?

Answer 62

1) TZDs 2) SUs 3) glinides 4) insulin

Question 63

Which 8 medication classes are taken orally?

Answer 63

- Metformin - SUs - Glinides - TZDs - AGIs - DPP-4 inhibitors - SGLT-2 inhibitors - Afrezza (inhaled)

Question 64

Which 3 medication classes are SC injectables?

Answer 64

- GLP-1 agonists - Amylin analogues - Insulin (basal, bolus)