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PDAT2 > 16 - DM GLP-1 RA Injectables > Flashcards

16 - DM GLP-1 RA Injectables Flashcards

1
Q

How do GLP-1 RA’s COMPLEMENT Basal Insulin?

A

•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%

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2
Q

GLP-1

MoA & Function

(Glucagon-Like Peptide-1 Receptor Agonist)

A

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

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3
Q

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

A

LIRAGLUTIDE

VICTOZA

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4
Q

Long Acting GLP-1 RA’s

Differences

A

GREATER Resistance to DPP4 Degradation

MORE effect on FBG

less effect on _gastric emptying & PPG_

preferred vs short acting (byetta) due to DOSING CONVENIENCE

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5
Q

Exenatide Long Acting

Brand + Dose + Extra

GLP-1 RA

A

Byetta also but is Short Acting

Bydureon

2 mg WEEKLY

avoid in pts w/ CrCL <30 ml/min

NVD + dizziness / HA / dyspepsia / constipation + hypoclycemia

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6
Q

Dosing Frequency of

Exenatide = Byetta

A

TWICE A DAY

GLP-1 RA

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7
Q

Pramlintide

ADVANTAGES

A

SYMLIN

(AmylinoMimetic = Synthetic Analog of Amylin)

WEIGHT LOSS

PPG REDUCTION

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8
Q

Lixisenatide

Brand + Dose + Extra

GLP-1 RA

A

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

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9
Q

Precautions for

GLP-1 RA’s

A

Pancreatitis

Pt education: persistant AB PAIN –> radiate to back or w/ N/V

hypoGlycemia

RENAL Impairment

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10
Q

Considerations of Pramlintide + Insulin

Symlin

A

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

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11
Q

Semaglutide

Brand + Dose + Extra

GLP1 - RA

A

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

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12
Q

Dulaglutide

Brand + Dose + Extra

GLP-1 RA

A

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

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13
Q

Disadvantages of

GLP-1 RA’s

A

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_

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14
Q

Exenatide Short Acting

Dose + Brand + Extra

GLP-1 RA’s

A

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

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15
Q

Soliqua 100/33

Dose / Indication / Name

3ml prefilled pen of

Insulin Glargine 100units/ml + Lixisenatide 33mcg/ml

(Lantus LA + Adlyxin)

A

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

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16
Q

Advantages of

GLP-1 RA’s

A

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

17
Q

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

A

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

18
Q

What INACTIVATES Incretins?

A

DPP4 Enzyme

–> inactive GLP-1 & GIP

occurs VERY QUICKLY after the release of these GUT Horomones

19
Q

Pramlintide for T2DM

Dosing

A

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

20
Q

Xultophy 100/3.6

Dose / Indication

3ml prefilled pen of Insulin

Insulin DEGLUDEC 100u/ml + LIRAGLUTIDE 3.6mcg/ml

(triseba LA basal insulin + Victoza)

A

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

21
Q

Pramlintide

Drug Type / Brand / Indication

A

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

22
Q

Dosing Frequency of:

Albiglutide = Tanzeum

Semaglutide = Ozempic

A

WEEKLY

GLP-1 RA’s

Dulaglutide = Trulicity

Exenatide = Bydureon

23
Q

What other DM medication should be discontinued when switching to a

GLP-1 RA?

A

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

24
Q

Pramlintide for T1DM

Dosing

A

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

25
Q

Amylin Function

A

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

26
Q

Liraglutide

Brand + Dose + Extra

GLP-1 RA

A

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

27
Q

Incretin Effect

Incretin = group of metabolic hormones, including GLP-1

A

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

28
Q

Pramlintide = Symlin

BOXED WARNING

A

SEVERE hypoGlycemia

seen within 3 hours following injection

PROPER EDUCATION

contraindicated in patient also with confirmed GASTROPARESIS

29
Q

Incretins

2 Main functions that result in decreased blood glucose

A

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

30
Q

DIfferences between

SHORT & LONG acting GLP-1 RA’s

A

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

31
Q

Pramlintide

Disadvantages

A
  • *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

32
Q

Dosing Frequency of

Liraglutide = Victoza

Lixisenatide = Adlyxin

A

DAILY

GLP-1 RA

33
Q

Exendin-4

A

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

PDAT2 (22 decks)

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