Lecture 13 Flashcards
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
- insulin
- preserve, gain, hypoglycemia
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
- hepatic
- intestinal, circulation
- GLP-1
- tissue, muscle
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 ___ )
- type 2
- CV
- hypoglycemia
- weight
- type I, ketoacidosis
- androgen, ovulation
metformin PK
T or F: metformin is excreted, changed in the urine
F: unchanged
metformin
Efficacy
- decrease A1C by ___ %
- decrease FBG by ___ mg/dL
- no weight gain and often weight loss ( ___ kg )
1.5-2%
60-80 mg/dL
2-3 kg
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 ___
- hypoglycemia
- TG, LDL, 8-15%
- weight
- fibrinolysis
- macrovascular
- stroke
- MI
Metformin
Disadvantages
- may cause ___ (rare, weak causal relationship)
- ___ side effects
- ___ deficiency
- ___ risk (controversial)
- lactic acidosis
- GI
- Vit B12
- dementia
Metformin
Contraindications
- renal dysfunction (look at ___ , not SCr)
- unstable ___
- alcoholics
- pts at risk for ___ acidosis (post ___ , ___ failure, COPD, shock, and contrast ___ )
- eGFR
- HF
- lactic, MI, hepatic, dye
T or F: metformin has shown some benefit in stable HF patients
T; decreased mortality, decrease HF, may be from effect on decreasing insulin resistance
contraindicated in pts with unstable HF
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
500, 850
- weekly, 250-500
2
- 2.55
Metformin Dosing - renal insufficiency
eGFR , 60-45
- safe to start therapy
- continue to use is already taking
- monitor SCr every ___ months
3-6 months
Metformin Dosing - renal insufficiency
eGFR 44-30
- starting metformin is ___ recommeded
- reduce dose by ____ % if already taking
- monitor SCr every ___ months
- NOT
- 50%
- 3 months
Metformin Dosing - renal insufficiency
eGFR < 30
- ___ start metformin
- ___ metformin if currently takig
- DO NOT
- STOP
SGLT2 - MOA
- SGLT2 is the major renal transporter for ___ reabsorption
- inhibition of SGLT2 leads to renal glucose ____ (up to ___ gm/day)
- glucose
- excretion, 60-90
pee out extra sugar
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 ___
- 2
- metformin, initial, 2
- HF, CKD
SGLT2 - Efficacy
A1C: decrease ___ - ___ %
FBG: decrease ___ - ___ mg/dL
PPG: decrease ___ - ___ mg/dL
weight: decrease ___ - ___ kg
BP: decrease SBP ___ - ___ mmHg and DBP: ___ - ___ mmHg
- 0.5-1.0%
- 25-35 mg/dL
- 40-60 mg/dL
- 1-5 kg
- 3-6, 2-3
SGLT2 - PK
- undergoes ___ by UGT1A9 and UGT2B4 to ___ metabolites
- ___ metabolism is minimal
- excreted mostly in ____ , but 1/3 in urine
- glucuronidation
- inactive
- CYP3A4
- feces
SGLT2
Adverse effects
- UTIs
- ___ infections
- increased ___
- ___ due to volume loss
- hyper___
- ___ cholesterol
- fungal (yeast)
- urination
- hypotension
- kalemia
- increased
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 ___
- 2, BG
- 3
- ertugliflozin
SGLT2
FDA warning: bone fractures and decreased BMD with ___
canagliflozin
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 ___ / ___
canagliflozin, dapagliflozin
- depletion, hypotension
- dehydration, diuretics, ACE-Is/ARBs
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
canagliflozin
- toes
- neuropathy, ulcers
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
- Fournier’s
- broad-spectrum, surgical
T or F: we can use SGLT2s on dialysis pts to improve kidney function
FALSE
they cannot pee bro
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
- 100, 300
- 100, albuminuria
- 100, 300
SGLT2 renal dosing - dapagliflozin
eGFR > 45
- ___ mg daily, MAX: ___ daily
eGFR < 25
- do not start
- if on therapy, ___ and monitor
- 5, 10
- continue
SGLT2 renal dosing - empagliflozin
eGFR > 30
- ___ mg daily, MAX: ___ daily
eGFR < 30
- do not start
- if on therapy, ___ and monitor
- 10, 25
- continue
SGLT2 renal dosing - ertugliflozin
eGFR > 60
- ___ mg daily, MAX: ___ mg daily
eGFR < 45
- do not start
- if on therapy, monitor
- if eGFR persistently low, ___
5, 15
discontinue
SGLT2 CV Benefits
CV benefits may be from a combination of decreased ___ , decreased ___ , and osmotic diuresis leading to a reduction in ___ volume
weight
BP
plasma
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
- 45%
- atherosclerosis
- glycemic
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 ___
dependent, B-cell
- B-cell
- glucagon, gastric, appetite
- DPP-V
- 1st, 2nd, meals
- BG
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 > ___ %
- metformin, initial
- insulin
- insulin
- 10%
GLP-1 Agonists - Efficacy
A1C: decrease ___ - ___ %
Weight: decrease ___ - ___ kg, may be up to ___ kg depending on dosing
- 0.7-1.6%
- 1.5-3 kg, 6 kg
GLP-1 Agonists
SE:
- nausea, vomiting, diarrhea
- acute ___
- black box warning for ___ cancer
- ___ disease
- avoid in pts with ___
- retinopathy
- pancreatitis
- thyroid
- gall bladder
- gastroparesis
GLP-1 Agonists
- short acting GLP-1s ( ___ and ___ ) have more effect on ___
- long acting have more effect on ___
- exenatide, lixisenatide, PPG
- FBG
GLP-1 Agonists
T or F: long acting GLP-1s are eliminated by the kindeys and are contraindicated with severe renal disease
F; short acting
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
- weekly
- 0.75, 4.5
- ESRD
- yes, attached
- single
- 2nd
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
- weekly
- 0.25mg , 4 weeks, 0.5 mg, 2 mg
- yes, in carton
- 56
- flow
- 0, 6
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 ___
- daily
- 0.6 mg, 7 days, 1.2 mg, 1.8 mg
- no
- 18
- 30 days
- 1st
- ESRD
exenatide (Byetta)
- frequency: ___
- dosing: ___ mcg x 1 ___, then ___ mcg
- avoid if CrCl < ___
- needles included? ___
- BID
- 5 mcg, month, 10 mcg
- 30
- no
exenatide (Bydureon Bcise)
- frequency: once ___
- dosing: ___ mg
- avoid if CrCl < ___
- needles included? ___
- once weekly
- 2 mg
- 30
- yes
lixisenatide (Adylyxin)
- frequency: once ___
- dosing: ___ mcg x ___ days, then ___ mcg
- avoid if eGFR < ___
- needles included?
- daily
- 10 mcg, 14 days, 20 mcg
- 15
- no
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
- 3 mg, 30 days, 7 mg
- 14 mg
- 30 min, 4 oz
T or F: GLP-1s have CV and renal benefit
True
REWIND, SUSTAIN-6, LEADER
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 ___
- 1st, 2nd
- glucagon, dependent
- gastric
- appetite
- CV
- weight loss
Dual GLP-1 and GIP - tirzepatide (Mounjaro)
Efficacy
A1C: decrease ___ - ___ %
FBG: decrease ___ - ___ mg/dL
PPG: decrease ___ - ___ mg/dL
Weight: decrease ___ - ___ kg
- 1.5-2.3 %
- 40-60 mg/dL
- 20-40 mg/dL
- 6-11 kg
Dual GLP-1 and GIP - tirzepatide (Mounjaro)
Adverse Effects
- N, V, D
- acute ___
- ___ tumors
- ___ disease
- ___ cardia (10-20% of pts)
- pancreatitis
- thyroid
- gall bladder
- tachycardia
Dual GLP-1 and GIP - tirzepatide (Mounjaro)
Dosing
- ___ mg once ___
- adjust once a month by ___ mg per ___ increments, up to ___ mg
- 2.5 mg, weekly
- 2.5 mg, week
- 15 mg
