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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
What strengths do metformin tablets come in?
500, 850, and 1000 mg
26
What is an appropriate initial metformin dose?
* 500 mg BID * 850 mg daily
27
How would you titrate metformin?
* Weekly or bi-monthly * Increase by 250-500 mg/day
28
Why was metformin XL recalled?
Unacceptable levels of NDMA (causes cancer and liver damage)
29
If a patient has an eGFR ≥60, how often would you recommend monitoring SCr?
Annually
30
How often would you monitor SCr in a patient taking metformin with an eGFR between 59 and 45?
Every 3-6 months
31
At what threshold is it not recommended to start metformin?
\<45
32
What should a patient do if they are already taking metformin, but their eGFR is between 44 and 30?
Reduce metformin dose by 50%
33
How often should you monitor SCr in a patient taking metformin with an eGFR between 44 and 30?
Every 3 months
34
List the 4 SGLT2 inhibitors, brand and generic.
* Canagliflozin (Invokana) * Dapagliflozin (Farxiga) * Empagliflozin (Jardiance) * Ertugliflozin (Steglatro)
35
What is the mechanism of action for SGLT2 inhibitors?
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
How much can SGLT2s decrease A1C?
0.6-1%
37
How much can SGLT2s decrease fasting blood glucose by?
25-35 mg/dl
38
How much can SGLT2s decrease PPG by?
40-60 mg/dl (MAJOR benefit)
39
What effect do SGLT2s have on weight?
Weight loss (1-4 kg)
40
How much do SGLT2s decrease systolic blood pressure?
3-6 mmHg
41
How much do SGLT2s decrease diastolic blood pressure?
2-3 mmHg
42
What are the most common adverse effects of SGLT2s?
* UTIs * Genital fungal infections * Increased urination * Other: hypotension, hyperkalemia, increased cholesterol
43
Explain the pharmacokinetics of SGLT2s.
* Undergoes glucuronidation by UGT1A9 and UGT2B4 to inactive metabolites * CYP3A4 metabolism is minimal * Excreted mostly in feces, but 1/3 in urine
44
Which FDA warnings exist for SGLT2s?
* DKA * Bone fractures, decreased BMD (canagliflozin) * AKI (canagliflozin and dapagliflozin) * Increased leg and foot amputations (canagliflozin) * Serious genital infections
45
For all intents and purposes, what is the #1 prescribed SGLT2?
Empagliflozin (Jardiance)
46
What eGFR threshold makes a patient ineligible to use any SGLT2s?
eGFR \<30 ml/min/1.73 m2
47
What SGLT2s (meds, doses, and max doses) are available to a patient with an eGFR \>60?
* **Canagliflozin (Invokana):** 100 mg daily (300 mg daily MAX) * **Ertugliflozin (Steglatro):** 5 mg daily (15 mg daily MAX)
48
What SGLT2s (meds, doses, and max doses) are available to a patient with an eGFR between 45 and 60?
* **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
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?
Canagliflozin (Invokana)
50
What is 3-point MACE?
Composite death from CV cause, nonfatal MI, or nonfatal stroke
51
SGLT2 inhibitors have ______ and ______ benefits.
Renal, heart failure
52
What are the 5 GLP-1 agonists (brand and generic)?
* Liraglutide (Victoza) * Dulaglutide (Trulicity) * Semaglutide (Ozempic, Rybelsus) * Exenatide (Byetta, Bydureon) * Lixisenatide (Adylyxin)
53
How does GLP-1 potentiate glucose-dependent insulin secretion?
By stimulating B-cell growth and differentiation and insulin gene expression
54
What are GLP-1 analogs' mechanism(s) of action?
* Inhibit B-cell death * Inhibit glucagon secretion * Delay gastric emptying and decrease appetite
55
GLP-1 agonists are resistant to which enzyme?
Dipeptidyl peptidase IV (the enzyme that inactivates natural GLP-1)
56
Why is it beneficial that GLP-1 agonists are glucose-dependent?
Leads to insulin release only in the presence of elevated blood sugar
57
Can GLP-1 agonists aid in weight loss? If yes, how much?
Yes
58
How much can GLP-1 agonists decrease A1C?
0.7-1.6%
59
What are the two "short-acting" GLP-1 analogs?
Exenatide and lixisenatide
60
When comparing short-acting and long-acting GLP-1 agonists, which are better at controlling PPG and which are better at controlling FBS?
* Short-acting are better for PPG * Long-acting are better for FBS
61
What are some adverse effects associated with GLP-1 agonists?
* Nausea * Vomiting * Acute pancreatitis * Thyroid c-cell tumors (black box warning)
62
Which GLP-1 agonists have needles included?
Trulicity and Ozempic
63
Which GLP-1 agonists are dosed once weekly?
Trulicity, Ozempic, and Bydureon Bcise
64
Which GLP-1 agonists are dosed daily?
Victoza and Adylyxin
65
What is the only GLP-1 agonist that is dosed BID?
Byetta
66
What is the dosing for Trulicity (dulaglutide)?
0.75 mg, 1.5 mg once weekly
67
What is the dosing for Victoza (liraglutide)?
0.6 mg daily for 1 week, then increase to 1.2 mg daily
68
What is the dosing for Ozempic (semaglutide)?
.25 mg weekly for 4 weeks, then .5-1 mg weekly
69
What is the dosing for Byetta (exenatide)?
5 mcg BID within 60 minutes before breakfast and dinner
70
What is the dosing for Adylyxin (lixisenatide)?
10 mcg daily for 2 weeks, then 20 mcg 1 hour before the first meal of the day
71
What is the dosing for Rybelsus (oral semaglutide)?
3 mg daily for 30 days, then 7 mg daily (up to 14 mg)
72
LEADER trial
CV benefits in liraglutide
73
SUSTAIN-6
CV benefits in semaglutide
74
REWIND
Dulaglutide and CV outcomes
75
Which drug class should you NEVER use in combination with GLP-1 agonists?
DPP-4 inhibitors
76
List the 4 DPP-4 inhibitors (brand and generic)
* Sitagliptin (Januvia) * Saxagliptin (Onglyza) * Linagliptin (Tradjenta) * Alogliptin (Nesina)
77

Fall 2020: Therapeutics 2 (11 decks)

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