16 - DM GLP-1 RA Injectables Flashcards
How do GLP-1 RA’s COMPLEMENT Basal Insulin?
•Basal insulin Analogs
•Control Both nocturnal + FPG
•Lower hypoglycemia risk vs NPH
- Moderate weight increase
- Achieve AIC targets in MOST 50-60%
•GLP1 Agonist
•Pronounced PPG CONTROL
•No hypoglycemia increase of risk
•WEIGHT LOWERING / neutral effects
achieve A1C target in 40-60%
GLP-1
MoA & Function
(Glucagon-Like Peptide-1 Receptor Agonist)
Activates GLP-1 Receptor, couple to AC by G-protein (Gs) in pancreatic beta cells
INCREASES intracellular cAMP –> INSULIN RELEASE, in presence of elevated glucose
- decrease* glucagon secretion
- delay* in gastric emptying
INCREASE in satiety
Which GLP-1 RA reduced CVD Death & Rate of death from any cause
also lowered non-fatal MI & Stroke, but differences were not significant
Leader Trial
LIRAGLUTIDE
VICTOZA
Long Acting GLP-1 RA’s
Differences
GREATER Resistance to DPP4 Degradation
MORE effect on FBG
less effect on _gastric emptying & PPG_
preferred vs short acting (byetta) due to DOSING CONVENIENCE
Exenatide Long Acting
Brand + Dose + Extra
GLP-1 RA
Byetta also but is Short Acting
Bydureon
2 mg WEEKLY
avoid in pts w/ CrCL <30 ml/min
NVD + dizziness / HA / dyspepsia / constipation + hypoclycemia
Dosing Frequency of
Exenatide = Byetta
TWICE A DAY
GLP-1 RA
Pramlintide
ADVANTAGES
SYMLIN
(AmylinoMimetic = Synthetic Analog of Amylin)
WEIGHT LOSS
PPG REDUCTION
Lixisenatide
Brand + Dose + Extra
GLP-1 RA
ADLYXIN
- *10mcg QD,** one hour b4 first meal
- *after 14 days,** 20mcg QD
NVD + HA + Dizziness + hypoGlycemia
no dose adj for renal impairment, just close monitoring
Missed dose -> administer 1 hour prior to next meal
Precautions for
GLP-1 RA’s
Pancreatitis
Pt education: persistant AB PAIN –> radiate to back or w/ N/V
hypoGlycemia
RENAL Impairment
Considerations of Pramlintide + Insulin
Symlin
BOTH SC so SEPERATE INJECTIONS @ SEPERATE SITES >2inches
do not MIX together
Admin using a U-100 insulin syringe
INJECT BEFORE EACH MAJOR MEAL
& snack >250kcal or >30g of CHO
Semaglutide
Brand + Dose + Extra
GLP1 - RA
OZEMPIC
0.25mg weekly for 4 weeks
0.5mg weekly
may increase to 1_mg weekly_ after another _4 weeks_
NVD + ab pain + constipation
no dose adj, no specific dosing time, <5 days miss dose can admin ASAP
Dulaglutide
Brand + Dose + Extra
GLP-1 RA
TRULICITY
0.75 mg Weekly
may increase to 1.5mg Qweek if needed
NVD + ab pain + decreased appitite
caution in renal dysfunction no dose adj tho
Missed doses can be readmin after within 72 hours
Disadvantages of
GLP-1 RA’s
GI SIDE EFFECTS = NVD
acute PANCREATITIS
Injectable / COST
Increase Heart Rate
Black Box Warning:
Tyroid C-Cell Tumors + MTC (medullary thyroid carcinoma)
_exception is IR Exenatide = BYETTA_
Exenatide Short Acting
Dose + Brand + Extra
GLP-1 RA’s
Bydureon is Long acting
Byetta
5mcg BID -> 10mcg BID
Admin 1 hour b4 AM & PM meals
MORE PRONOUNCED EFFECT ON PPG HYPERglycemia
avoid in pts w/ CrCL <30 ml/min
NVD + dizziness / HA / dyspepsia / constipation + hypoclycemia
Soliqua 100/33
Dose / Indication / Name
3ml prefilled pen of
Insulin Glargine 100units/ml + Lixisenatide 33mcg/ml
(Lantus LA + Adlyxin)
Indicated for T2DM *inadequately controlled* on basal insulin <60 units/qd or Lixisenatide
inadequate control <30units insulin or lixisenatide
starting dose is 15 units QD
inadequate control on 30-60 units of basal insulin
starting dose = 30 units QD
MAX DOSE = 60 units
Advantages of
GLP-1 RA’s
Weight Reduction
PPG REDUCTION
Significant AIC Reduction 0.5-1%
minimal risk of hypoglycemia
Associated w/ lower CVD event rate & Mortality in patients w/ CVD
GLP-1 RA
Indication
Not 1st line therapy for patients inadequately controlled on diet/exercise
Adjunct to Diet+Exercise, to improve glycemic control in adults w/ T2DM
Dual or Triple Therapy
w/ Metormin or other DM med (except DPP-4’s) when PRIMARY consideration is:
WEIGHT LOSS** or **Avoiding hypoGlycemia
A1C is CLOSE to target (within 1-1.5%)
cost or injection is NOT a major barrier
if PMH = MI or Stroke –> chose Liraglutide + Metformin
What INACTIVATES Incretins?
DPP4 Enzyme
–> inactive GLP-1 & GIP
occurs VERY QUICKLY after the release of these GUT Horomones
Pramlintide for T2DM
Dosing
Symlin = Amylin Analog
FIRST = REDUCE MEALTIME INSULIN DOSE BY 50%
start 60mcg subQ
immediately PRIOR to each major meal
may INCREASE to 120mcg
if no clinically significant NAUSEA occured for the last 3 days
Xultophy 100/3.6
Dose / Indication
3ml prefilled pen of Insulin
Insulin DEGLUDEC 100u/ml + LIRAGLUTIDE 3.6mcg/ml
(triseba LA basal insulin + Victoza)
Indicated for T2DM *inadequately controlled* on
basal insulin <50 units/qd or < 1.8mg Liraglutide QD
inadequate control <30units insulin or lixisenatide
starting dose is 16 units QD
with or without food
MAX DOSE = 50 units
Pramlintide
Drug Type / Brand / Indication
SYMLIN
AmylinoMimetic = Synthetic Analog of Amylin
Indicated for BOTH T1DM & T2DM** patients who use **Mealtime insulin, and has FAILED to reach glycemic control despite optimal insulin therapy.
avg A1C reduction is only ~0.6% not very significant
Dosing Frequency of:
Albiglutide = Tanzeum
Semaglutide = Ozempic
WEEKLY
GLP-1 RA’s
Dulaglutide = Trulicity
Exenatide = Bydureon
What other DM medication should be discontinued when switching to a
GLP-1 RA?
DPP4 INHIBITORS LASS
both reduce PPG & act on the incretin system
Sitagliptin
Januvia - 100mg qd
Saxagliptin
Onglyza - 2.5-5mg qd
Linagliptin
Tradjenta - 5mg qd, no dose adjustment
Alogliptin
Nesina - 25mg qd
Pramlintide for T1DM
Dosing
Symlin = Amylin Analog
FIRST = REDUCE MEALTIME INSULIN DOSE BY 50%
start 15mcg subQ
immediately PRIOR to each major meal
TITRATE up by 15mcg increments (30->45->60mcg)
MAX = 60mcg prior to each meal
Amylin Function
Peptide Hormone that is CO-SECRETED w insulin by the pancreas
Reduce PPG output
liver activity
Regulate Gastric Emptying
Stomach activity
INCREASE SATIETY –> reduce food intake & weight
Brain activity
Liraglutide
Brand + Dose + Extra
GLP-1 RA
VICTOZA
0.6 mg QD for 1 week
then 1.2 mg QD –> 1.8mg QD if needed
TITRATION REQUIRED, restart @ 0.6mg if miss >3 doses
N / D / HA (headache)
Caution in pts w/ renal dysfunction, no dose adj tho
Incretin Effect
Incretin = group of metabolic hormones, including GLP-1
Substantually MORE insulin secreted in response to oral glucose, in comparison to IV Glucose
Meal -> intestinal GLP-1 Release ->
active GLP-1 -> DPP4 -> inactive GLP1
(inactivation occurs VERY QUICKLY, t1/2 = 1-2min)
Hypothesized that glucose in the digestive tract activated a feed forward mechanism that increased insulin secretion, anticipating the rise in blood glucose following absorption of ingested CHO
Pramlintide = Symlin
BOXED WARNING
SEVERE hypoGlycemia
seen within 3 hours following injection
PROPER EDUCATION
contraindicated in patient also with confirmed GASTROPARESIS
Incretins
2 Main functions that result in decreased blood glucose
Glucose-Dependent INCREASED insulin from beta cells
–> INCREASED glucose uptake by muscles
Glucose-dependent decreased glucagon from alpha cells (GLP-1 only)
–> decreased glucose production by liver
DIfferences between
SHORT & LONG acting GLP-1 RA’s
Exenatide vs Exenatide LAR + Liraglutide + Dulaglutide
A1C reduction: Modest vs Strong
FPG reduction: Modest vs Strong
PPG reduction: Strong vs Modest
Same gastric emptying and BP reduction
Body Weight reduction: 1-5kg vs 2-5kg
Pramlintide
Disadvantages
- *Screen Drugs affecting GI motility**
- may delay absorption, admin 1 hour before or 2 hours after oral meds*
Only a Modest A1C Efficacy ~0.6%, very little compared to others
hypoGlycemia, need to reduce insulin dose
GI effects = N/V
FREQUENT DOSING SCHEDULE
injectable, do not mix with insulin
Dosing Frequency of
Liraglutide = Victoza
Lixisenatide = Adlyxin
DAILY
GLP-1 RA
Exendin-4
Peptide that was closely related to GLP-1, discovered in the saliva of Gila monster
RESISTANT to degradation by DPP4
NOT actively secreted by the KIDNEY
BYETTA = first GLP-1 Receptor agonist
