Lecture 13

Question 1

Non-Insulin Treatments

• none of these products are as effective as ___ in terms of glucose lowering effect
• ideal treatments would ___ beta cell function, prevent weight ___ , prevent ____ , and improve/not worsen concomitant disease states

Answer 1

• insulin
• preserve, gain, hypoglycemia

Question 2

Metformin

MOA:
- decrease ___ glucose production
- increase ___ glucose utilization and decrease glucose uptake into ___
- increase ___ secretion
- modest effect on increasing ___ uptake and utilization of glucose by the ___

Glucophage, Fortamet, or Glumetza

Answer 2

• hepatic
• intestinal, circulation
• GLP-1
• tissue, muscle

Question 3

Metformin

Clinical applications
- adjunct to diet in uncontrolled type ___ pts
- in combination with insulin and non-insulin agents
- reduce __ death
- minimal ___
- ___ neutral

Off label:
- overweight type ___ with low risk of ___
- PCOS (lowers ___ and increase ___ )

Answer 3

• type 2
• CV
• hypoglycemia
• weight
• type I, ketoacidosis
• androgen, ovulation

Question 4

metformin PK

T or F: metformin is excreted, changed in the urine

Answer 4

F: unchanged

Question 5

metformin

Efficacy
- decrease A1C by ___ %
- decrease FBG by ___ mg/dL
- no weight gain and often weight loss ( ___ kg )

Answer 5

1.5-2%
60-80 mg/dL
2-3 kg

Question 6

Metfomrin

Advantages
- less risk for ___ due to no insulin release
- deceased lipids ( ___ and ___ ) by ___ %
- ___ loss/neutral
- cost effective
- increased ___ = CV protection
- decrease ___ complications and total mortality
- decrease risk of ___ compared to insulin and SUs
- decrease diabetes related death and ___

Answer 6

• hypoglycemia
• TG, LDL, 8-15%
• weight
• fibrinolysis
• macrovascular
• stroke
• MI

Question 7

Metformin

Disadvantages
- may cause ___ (rare, weak causal relationship)
- ___ side effects
- ___ deficiency
- ___ risk (controversial)

Answer 7

• lactic acidosis
• GI
• Vit B12
• dementia

Question 8

Metformin

Contraindications
- renal dysfunction (look at ___ , not SCr)
- unstable ___
- alcoholics
- pts at risk for ___ acidosis (post ___ , ___ failure, COPD, shock, and contrast ___ )

Answer 8

• eGFR
• HF
• lactic, MI, hepatic, dye

Question 9

T or F: metformin has shown some benefit in stable HF patients

Answer 9

T; decreased mortality, decrease HF, may be from effect on decreasing insulin resistance

contraindicated in pts with unstable HF

Question 10

Metformin Dosing - initial and max dose

initial - ___ mg po BID or ___ daily, with meals
- titrate dose ___ or bi-monthly by ___ - ___ mg/day

Max: ___ gm/day
- package insert says ___ gm/day

Answer 10

500, 850
- weekly, 250-500

2
- 2.55

Question 11

Metformin Dosing - renal insufficiency

eGFR , 60-45
- safe to start therapy
- continue to use is already taking
- monitor SCr every ___ months

Answer 11

3-6 months

Question 12

Metformin Dosing - renal insufficiency

eGFR 44-30
- starting metformin is ___ recommeded
- reduce dose by ____ % if already taking
- monitor SCr every ___ months

Answer 12

• NOT
• 50%
• 3 months

Question 13

Metformin Dosing - renal insufficiency

eGFR < 30
- ___ start metformin
- ___ metformin if currently takig

Answer 13

• DO NOT
• STOP

Question 14

SGLT2 - MOA

• SGLT2 is the major renal transporter for ___ reabsorption
• inhibition of SGLT2 leads to renal glucose ____ (up to ___ gm/day)

Answer 14

• glucose
• excretion, 60-90

pee out extra sugar

Question 15

SGLT2

clinical application
- adjunct to diet and exercise in type ___ pts
- recommended with or without ___ as apropriate ____ therapy for individuals with type ___ diabetes at high risk for ACVD, ___ , and/or ___

Answer 15

• 2
• metformin, initial, 2
• HF, CKD

Question 16

SGLT2 - Efficacy

A1C: decrease ___ - ___ %
FBG: decrease ___ - ___ mg/dL
PPG: decrease ___ - ___ mg/dL
weight: decrease ___ - ___ kg
BP: decrease SBP ___ - ___ mmHg and DBP: ___ - ___ mmHg

Answer 16

• 0.5-1.0%
• 25-35 mg/dL
• 40-60 mg/dL
• 1-5 kg
• 3-6, 2-3

Question 17

SGLT2 - PK

• undergoes ___ by UGT1A9 and UGT2B4 to ___ metabolites
• ___ metabolism is minimal
• excreted mostly in ____ , but 1/3 in urine

Answer 17

• glucuronidation
• inactive
• CYP3A4
• feces

Question 18

SGLT2

Adverse effects
- UTIs
- ___ infections
- increased ___
- ___ due to volume loss
- hyper___
- ___ cholesterol

Answer 18

• fungal (yeast)
• urination
• hypotension
• kalemia
• increased

Question 19

SGLT2

FDA warning: DKA
- most pts were type ___ with mildly elevated ___
- factors: illness, dehydration, decreased insulin dose
- hold SGLT2 ___ days before surgery, resume when oral intake is back to normal baseline
- hold 4 days before surgery for ___

Answer 19

• 2, BG
• 3
• ertugliflozin

Question 20

SGLT2

FDA warning: bone fractures and decreased BMD with ___

Answer 20

canagliflozin

Question 21

SGLT2

FDA warning: AKI with ___ and ___
- 50% of cases started within one month of treatment initiation and improved after treatment discontinuation
- likely due to volume ___and ___
- caution in pts with potential for ___ or if they are on ____ , NSAIDs, or ___ / ___

Answer 21

canagliflozin, dapagliflozin
- depletion, hypotension
- dehydration, diuretics, ACE-Is/ARBs

Question 22

SGLT2

FDA warning: increased leg and foot amputations with ___
- mostly affecting the ___
- use caution with pts with prior amputation, PVD, ___, and foot __

warning removed in 2020

Answer 22

canagliflozin
- toes
- neuropathy, ulcers

Question 23

SGLT2

FDA warning: serious genital infections
- necrotizing fascitis of perineum ( ___ gangrene)
- urologic emergency, requires ___ antibiotics and immediate ___ intervention
- pts should seek medical attention if there is amy tenderness, redness, swelling, fever, fatigue, and malaise

Answer 23

• Fournier’s
• broad-spectrum, surgical

Question 24

T or F: we can use SGLT2s on dialysis pts to improve kidney function

Answer 24

FALSE

they cannot pee bro

Question 25

# SGLT2 renal dosing - canagliflozin eGFR > 60 - ___ mg daily, MAX: ___ mg daily eGFR 30-60 - MAX: ___ mg daily if no ___ eGFR < 30 - do not start - if already taking, may use ___ mg daily if albuminurial > ___ mg/dL

Answer 25

- 100, 300 - 100, albuminuria - 100, 300

Question 26

# SGLT2 renal dosing - dapagliflozin eGFR > 45 - ___ mg daily, MAX: ___ daily eGFR < 25 - do not start - if on therapy, ___ and monitor

Answer 26

- 5, 10 - continue

Question 27

# SGLT2 renal dosing - empagliflozin eGFR > 30 - ___ mg daily, MAX: ___ daily eGFR < 30 - do not start - if on therapy, ___ and monitor

Answer 27

- 10, 25 - continue

Question 28

# SGLT2 renal dosing - ertugliflozin eGFR > 60 - ___ mg daily, MAX: ___ mg daily eGFR < 45 - do not start - if on therapy, monitor - if eGFR persistently low, ___

Answer 28

5, 15 discontinue

Question 29

# SGLT2 CV Benefits CV benefits may be from a combination of decreased ___ , decreased ___ , and osmotic diuresis leading to a reduction in ___ volume

Answer 29

weight BP plasma

Question 30

# SGLT2 Renal Benefits reduce worsening renal function, end stage renal disease or renal death by ___ % - benefits seen in pts with/without ___ - benefits independent of improvement in ___ control

Answer 30

- 45% - atherosclerosis - glycemic

Question 31

# GLP-1 Agonists MOA: GLP-1 potentiates glucose-___ insulin secretion by stimulating ___ growth and differentiation and insulin gene expression - inhibit ___ death - inhibits ___ secretion, delays ___ emptying, and decreases ___ - resistant to ___ - increases ___ and ___ phase insulin secretion after ___ occur - leads to insulin release only in presence of elevated ___

Answer 31

dependent, B-cell - B-cell - glucagon, gastric, appetite - DPP-V - 1st, 2nd, meals - BG

Question 32

# GLP-1 Agonists clinical applications: - recommended with or without ___ as appropriate ___ therapy for individuals with type II with high ACVD, HF, and/or CKD - for type II preferred over ___ if possible - if ___ is used, combo therapy with GLP-1 is recommended for greater efficacy and durability of. - choose insulin first when A1C is > ___ %

Answer 32

- metformin, initial - insulin - insulin - 10%

Question 33

# GLP-1 Agonists - Efficacy A1C: decrease ___ - ___ % Weight: decrease ___ - ___ kg, may be up to ___ kg depending on dosing

Answer 33

- 0.7-1.6% - 1.5-3 kg, 6 kg

Question 34

# GLP-1 Agonists SE: - nausea, vomiting, diarrhea - acute ___ - black box warning for ___ cancer - ___ disease - avoid in pts with ___ - retinopathy

Answer 34

- pancreatitis - thyroid - gall bladder - gastroparesis

Question 35

# GLP-1 Agonists - short acting GLP-1s ( ___ and ___ ) have more effect on ___ - long acting have more effect on ___

Answer 35

- exenatide, lixisenatide, PPG - FBG

Question 36

# GLP-1 Agonists T or F: long acting GLP-1s are eliminated by the kindeys and are contraindicated with severe renal disease

Answer 36

F; short acting

Question 37

# dulaglutide (Trulicity) - frequency: once ___ - dosing: ___ mg up to ___ mg - use in caution in ___ - needles included? ___ - available in ___ pens - at ___ click, medication has been administered, you can remove pen

Answer 37

- weekly - 0.75, 4.5 - ESRD - yes, attached - single - 2nd

Question 38

# semaglutide (Ozempic) - frequency: once ___ - dosing: ___ mg x ___ weeks, then ___ mg up to ___ mg - needles included? ___ - after 1st use, pen can be stored at ___ days at room temp/fridge - check ___ with each new pen - during injection, push button until dose counter goes back to ___ and count to ___ seconds before removing the pen

Answer 38

- weekly - 0.25mg , 4 weeks, 0.5 mg, 2 mg - yes, in carton - 56 - flow - 0, 6

Question 39

# liraglutide (Victoza) - frequency: once ___ - dosing: ___ mg x ___ days, then ___ mg up to ___ mg - needles included? ___ - available in prefilled pens with ___ mg per pen - discard unused medication after ___ days - only prime prior to ___ injection - limited experience in ___

Answer 39

- daily - 0.6 mg, 7 days, 1.2 mg, 1.8 mg - no - 18 - 30 days - 1st - ESRD

Question 40

# exenatide (Byetta) - frequency: ___ - dosing: ___ mcg x 1 ___, then ___ mcg - avoid if CrCl < ___ - needles included? ___

Answer 40

- BID - 5 mcg, month, 10 mcg - 30 - no

Question 41

# exenatide (Bydureon Bcise) - frequency: once ___ - dosing: ___ mg - avoid if CrCl < ___ - needles included? ___

Answer 41

- once weekly - 2 mg - 30 - yes

Question 42

# lixisenatide (Adylyxin) - frequency: once ___ - dosing: ___ mcg x ___ days, then ___ mcg - avoid if eGFR < ___ - needles included?

Answer 42

- daily - 10 mcg, 14 days, 20 mcg - 15 - no

Question 43

# semaglutide (Rybelsus) - ___ mg po daily x ___ days, then increase to __ mg daily - can increase to ___ mg daily if needed - take ___ min before first food/beverage/other oral medications with no more than ___ oz plain water

Answer 43

- 3 mg, 30 days, 7 mg - 14 mg - 30 min, 4 oz

Question 44

T or F: GLP-1s have CV and renal benefit

Answer 44

True | REWIND, SUSTAIN-6, LEADER

Question 45

# Dual GLP-1 and GIP - tirzepatide (Mounjaro) MOA: - enhances ___ and ___ phase insulin sectrion - reduces ___ levels, in a glucose - ___ manner - delays ___ emptying - decreases ___ - ___ outcomes expected 2025 - marketed especially for ___

Answer 45

- 1st, 2nd - glucagon, dependent - gastric - appetite - CV - weight loss

Question 46

# Dual GLP-1 and GIP - tirzepatide (Mounjaro) Efficacy A1C: decrease ___ - ___ % FBG: decrease ___ - ___ mg/dL PPG: decrease ___ - ___ mg/dL Weight: decrease ___ - ___ kg

Answer 46

- 1.5-2.3 % - 40-60 mg/dL - 20-40 mg/dL - 6-11 kg

Question 47

# Dual GLP-1 and GIP - tirzepatide (Mounjaro) Adverse Effects - N, V, D - acute ___ - ___ tumors - ___ disease - ___ cardia (10-20% of pts)

Answer 47

- pancreatitis - thyroid - gall bladder - tachycardia

Question 48

# Dual GLP-1 and GIP - tirzepatide (Mounjaro) Dosing - ___ mg once ___ - adjust once a month by ___ mg per ___ increments, up to ___ mg

Answer 48

- 2.5 mg, weekly - 2.5 mg, week - 15 mg