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Fall 2020: Therapeutics 2 > Dr. Kania's Non-Insulin Lectures > Flashcards

Dr. Kania's Non-Insulin Lectures Flashcards

1
Q

What are the characteristics of an ideal non-insulin treatment?

A
  • Preserves beta cell function
  • Prevents weight gain
  • Prevents hypoglycemia
  • Improves/not worsens concomitant disease states
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2
Q

What are the two antidiabetic drug classes that are injectable?

A
  • GLP-1 agonists
  • Amylin mimetics
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3
Q

Which 2 drugs/drug classes decrease hepatic glucose output?

A

Metformin and thiazolidinediones

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4
Q

What 3 drug classes enhance insulin secretion?

A

Sulfonylureas, meglitinides, and incretins

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5
Q

What 2 drug classes decrease glucagon secretion?

A

Incretins and amylin

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6
Q

What 2 drug classes improve appetite control?

A

Incretins and amylins

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7
Q

What drug class has a risk of lipotoxicity?

A

Thiazolidinediones

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8
Q

What drug class decreases glucose reabsorption?

A

SGLT2 inhibitors

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9
Q

Which 2 drugs increase glucose uptake and utilization?

A

Thiazolidinediones and metformin

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10
Q

What is metformin’s mechanism of action?

A
  • Decreases hepatic glucose production
  • Increases intestinal glucose utilization
  • Decreases glucose uptake into circulation
  • Can increase GLP-1 secretion
  • Modest effect on increasing tissue uptake and utilization of glucose by muscle
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11
Q

What are the 2 off-label uses for metformin?

A
  • T1DM patients who are overweight with low ketoacidosis risk
  • PCOS (lowers androgens and increases ovulation)
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12
Q

How much does metformin lower A1C by?

A

1.5-2%

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13
Q

How much can metformin reduce fasting blood glucose?

A

60-80 mg/dl

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14
Q

Is metformin renally or hepatically secreted?

A

Renally (excreted unchanged in the urine)

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15
Q

Does metformin have a low or high risk of hypoglycemia?

A

Low risk, due to no insulin release

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16
Q

Other than low risk of hypoglycemia, describe the other advantages of metformin.

A
  • Decreases triglycerides and LDL by 8-15%
  • Weight neutral to possible weight loss (2-3 kg)
  • Cheap
  • CV protection (increased fibrinolysis)
  • Decreases mascrovascular complications and mortality
  • Lower stroke risk than insulin and SUs
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17
Q

What is the most common (and arguably the worst) side effect of metformin?

A

GI effects (diarrhea, nausea/vomiting, flatulence)

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18
Q

What recommendations would you make to reduce the GI effects of metformin?

A

Take with the largest meal of the day and titrate doses

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19
Q

How big of a concern is lactic acidosis in patients taking metformin?

A

Not a major issue; weak causal relationship

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20
Q

When is metformin contraindicated?

A
  • Heart failure (especially NYHA class III and IV)
  • eGFR <30 ml/min/1.73 m2
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21
Q

What patient groups are at an increased risk of lactic acidosis with metformin?

A
  • Alcoholics
  • Post-MI
  • Hepatic failure
  • Surgery/procedure patients
  • COPD exacerbations/end-of-life
  • Shock
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22
Q

How long should you hold metformin in patients undergoing a surgery or procedure?

A

Hold metformin 1-2 days before and then 2 days after (depending on patient status)

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23
Q

What vitamin deficiency is most common with metformin?

A

Vitamin B12

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24
Q

What is the MAXIMUM clinical dose for metformin (grams/day)?

A

2 grams per day

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25
Q

What strengths do metformin tablets come in?

A

500, 850, and 1000 mg

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26
Q

What is an appropriate initial metformin dose?

A
  • 500 mg BID
  • 850 mg daily
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27
Q

How would you titrate metformin?

A
  • Weekly or bi-monthly
  • Increase by 250-500 mg/day
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28
Q

Why was metformin XL recalled?

A

Unacceptable levels of NDMA (causes cancer and liver damage)

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29
Q

If a patient has an eGFR ≥60, how often would you recommend monitoring SCr?

A

Annually

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30
Q

How often would you monitor SCr in a patient taking metformin with an eGFR between 59 and 45?

A

Every 3-6 months

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31
Q

At what threshold is it not recommended to start metformin?

32
Q

What should a patient do if they are already taking metformin, but their eGFR is between 44 and 30?

A

Reduce metformin dose by 50%

33
Q

How often should you monitor SCr in a patient taking metformin with an eGFR between 44 and 30?

A

Every 3 months

34
Q

List the 4 SGLT2 inhibitors, brand and generic.

A
  • Canagliflozin (Invokana)
  • Dapagliflozin (Farxiga)
  • Empagliflozin (Jardiance)
  • Ertugliflozin (Steglatro)
35
Q

What is the mechanism of action for SGLT2 inhibitors?

A

SGLT2 transports renal glucose to aid in reabsorption, so inhibiting it leads to renal glucose excretion (up to 60-90 grams/day) as the patient pees out excess sugar

36
Q

How much can SGLT2s decrease A1C?

37
Q

How much can SGLT2s decrease fasting blood glucose by?

A

25-35 mg/dl

38
Q

How much can SGLT2s decrease PPG by?

A

40-60 mg/dl (MAJOR benefit)

39
Q

What effect do SGLT2s have on weight?

A

Weight loss (1-4 kg)

40
Q

How much do SGLT2s decrease systolic blood pressure?

41
Q

How much do SGLT2s decrease diastolic blood pressure?

42
Q

What are the most common adverse effects of SGLT2s?

A
  • UTIs
  • Genital fungal infections
  • Increased urination
  • Other: hypotension, hyperkalemia, increased cholesterol
43
Q

Explain the pharmacokinetics of SGLT2s.

A
  • Undergoes glucuronidation by UGT1A9 and UGT2B4 to inactive metabolites
  • CYP3A4 metabolism is minimal
  • Excreted mostly in feces, but 1/3 in urine
44
Q

Which FDA warnings exist for SGLT2s?

A
  • DKA
  • Bone fractures, decreased BMD (canagliflozin)
  • AKI (canagliflozin and dapagliflozin)
  • Increased leg and foot amputations (canagliflozin)
  • Serious genital infections
45
Q

For all intents and purposes, what is the #1 prescribed SGLT2?

A

Empagliflozin (Jardiance)

46
Q

What eGFR threshold makes a patient ineligible to use any SGLT2s?

A

eGFR <30 ml/min/1.73 m2

47
Q

What SGLT2s (meds, doses, and max doses) are available to a patient with an eGFR >60?

A
  • Canagliflozin (Invokana): 100 mg daily (300 mg daily MAX)
  • Ertugliflozin (Steglatro): 5 mg daily (15 mg daily MAX)
48
Q

What SGLT2s (meds, doses, and max doses) are available to a patient with an eGFR between 45 and 60?

A
  • Canagliflozin (Invokana): MAX 100 mg daily if no albuminuria
  • Dapagliflozin (Farxiga): 5 mg daily (MAX 10 mg daily)
  • Empagliflozin (Jardiance): 10 mg daily (MAX 25 mg daily)
49
Q

What is the only SGLT2 that does not need to be discontinued when eGFR is between 30 and 45, so long as albuminuria is >300 mg/dl?

A

Canagliflozin (Invokana)

50
Q

What is 3-point MACE?

A

Composite death from CV cause, nonfatal MI, or nonfatal stroke

51
Q

SGLT2 inhibitors have ______ and ______ benefits.

A

Renal, heart failure

52
Q

What are the 5 GLP-1 agonists (brand and generic)?

A
  • Liraglutide (Victoza)
  • Dulaglutide (Trulicity)
  • Semaglutide (Ozempic, Rybelsus)
  • Exenatide (Byetta, Bydureon)
  • Lixisenatide (Adylyxin)
53
Q

How does GLP-1 potentiate glucose-dependent insulin secretion?

A

By stimulating B-cell growth and differentiation and insulin gene expression

54
Q

What are GLP-1 analogs’ mechanism(s) of action?

A
  • Inhibit B-cell death
  • Inhibit glucagon secretion
  • Delay gastric emptying and decrease appetite
55
Q

GLP-1 agonists are resistant to which enzyme?

A

Dipeptidyl peptidase IV (the enzyme that inactivates natural GLP-1)

56
Q

Why is it beneficial that GLP-1 agonists are glucose-dependent?

A

Leads to insulin release only in the presence of elevated blood sugar

57
Q

Can GLP-1 agonists aid in weight loss? If yes, how much?

58
Q

How much can GLP-1 agonists decrease A1C?

59
Q

What are the two “short-acting” GLP-1 analogs?

A

Exenatide and lixisenatide

60
Q

When comparing short-acting and long-acting GLP-1 agonists, which are better at controlling PPG and which are better at controlling FBS?

A
  • Short-acting are better for PPG
  • Long-acting are better for FBS
61
Q

What are some adverse effects associated with GLP-1 agonists?

A
  • Nausea
  • Vomiting
  • Acute pancreatitis
  • Thyroid c-cell tumors (black box warning)
62
Q

Which GLP-1 agonists have needles included?

A

Trulicity and Ozempic

63
Q

Which GLP-1 agonists are dosed once weekly?

A

Trulicity, Ozempic, and Bydureon Bcise

64
Q

Which GLP-1 agonists are dosed daily?

A

Victoza and Adylyxin

65
Q

What is the only GLP-1 agonist that is dosed BID?

66
Q

What is the dosing for Trulicity (dulaglutide)?

A

0.75 mg, 1.5 mg once weekly

67
Q

What is the dosing for Victoza (liraglutide)?

A

0.6 mg daily for 1 week, then increase to 1.2 mg daily

68
Q

What is the dosing for Ozempic (semaglutide)?

A

.25 mg weekly for 4 weeks, then .5-1 mg weekly

69
Q

What is the dosing for Byetta (exenatide)?

A

5 mcg BID within 60 minutes before breakfast and dinner

70
Q

What is the dosing for Adylyxin (lixisenatide)?

A

10 mcg daily for 2 weeks, then 20 mcg 1 hour before the first meal of the day

71
Q

What is the dosing for Rybelsus (oral semaglutide)?

A

3 mg daily for 30 days, then 7 mg daily (up to 14 mg)

72
Q

LEADER trial

A

CV benefits in liraglutide

73
Q

SUSTAIN-6

A

CV benefits in semaglutide

74
Q

REWIND

A

Dulaglutide and CV outcomes

75
Q

Which drug class should you NEVER use in combination with GLP-1 agonists?

A

DPP-4 inhibitors

76
Q

List the 4 DPP-4 inhibitors (brand and generic)

A
  • Sitagliptin (Januvia)
  • Saxagliptin (Onglyza)
  • Linagliptin (Tradjenta)
  • Alogliptin (Nesina)

Fall 2020: Therapeutics 2 (11 decks)

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