Diabetes: Lecture 3 Flashcards
Key factors to consider when selecting an agent for T2DM
Efficacy in lowering A1c Cost Effect on weight Side effects Hypoglycemia risk
highest A1c efficacy?
GLP-1 RA (1-1.5% decrease)
A1c efficacy less than 1%?
SGLT2i and DPP-4 Inhib
Lowest cost T2DM drug?
Generally Sulfonylureas and Pioglitazone
Drugs causing Weight Change?
Loss = SGLT2i, GLP1-RA (Most) Gain = Sulfonylureas, Pioglitazone Neutral = DPP4i
Drug with Hypoglycemia risk?
Sulfonylureas
Drugs to consider based on cost?
Sulfonylurea (Glipizide or Glyburide)
Pioglitazone (Actos)
Drugs to consider based on weight changes?
GLP1-RA (Most loss)
SGLT2i
Weight loss with GLP-1RA
Ozempic>Victoza>Trulicity> Byetta
Drugs in which you wanna minimize hypoglycemia?
Any meds except sulfonylureas.
Drugs that target Fasting BG levels?
Metformin
Basal Insulin
NPH insulin
Drugs that target post prandial BG levels?
DPP-4 Inhib
Exenatide (Byetta)
Regaglinide (Prandin)
Prandial insulin
Drugs that have mixed BG level targets
Sulfonylureas Long acting GLP1-RA TZDs SGLT2i Mixed insulins
GLP1-RA Mechanism of Action
Increase glucose dependent insulin secretion
Suppresses post-prandial glucagon secretion
Decreases gastric emptying time
Increase satiety
** Increase Glucose dependent insulin secretion**
GLP1-RA are as effective as….
adding both prandial and basal insulin
similar BG effects, with less hypoglycemia, weight loss instead of gain, but more GI SE
Barriers to using GLP1-RA
Cost
injectable
can be too complicated for some
Typical place in therapy of GLP1-RA?
add on to lifestyle changes and when 1/2 agents +/- basal insulin are insufficient
considered preferred injection over basal insulin in most patients
Bydureon, Trulicity, Ozempic counseling
Once weekly, same day/time of the week. If miss dose inject when remember or within 3 days (5 for Ozempic)
Bydureon Titration
1 dose, no titration
2 mg SC once weekly
Trulicity Titration
0.75 mg 1st month
increase to 1.5 after 4 weeks, then 3mg, 4.5mg at 4 week interval
Ozempic Titration
0.25mg wkly for 4 weeks, after 4 week increase to 0.5mg, then after min 4 week can increase to 1mg
Victoza Titration
0.6mg/day week 1, 1.2mg/day week 2, 1.8mg/day week 3
Counseling for titrations
review each dose per week
GI SE usually light, go away..if not good then do extra week at the dose before increasing
Dose adjustment with Renal function and GLP1-RA
Caution w/ Bydureon…should not be used in <30ml/min
No dose adjustments in others
No hepatic adjustments for any
Oral Semaglutide (Rybelsus) Titration
Start 3mg/day for 30 days
increase to 7mg/day for 30 days
increase to 14mg/day if need more BG lowering
No renal or hepatic adjustments
Oral Semaglutide (Rybelsus) Patient education
take 30min prior to 1st food/drink/other meds
Taken with sip of water <4oz
swallow whole
schedule meds with similar dosing around this time
which injectable has separate pen needle?
Victoza/Ozempic
Victoza needs separate script, Ozempic doesn’t since they come in box
Which injectables don’t need separate pen needles?
Trulicity
Possible side effects GLP1-RA
Nausea
GI
Possible Pancreatitis (Don’t start if they have history of Gallstones)
Bydureon ER side effects
small nodules/lumps where inject
Itchy at first, may be transient
Ozempic Side effects
Risk of DM retinopathy complications
When not to use GLP1-RA
Thyroid C-cell tumors Severely elevated TG Gallbladder disease Pancreatitis Alcoholism
DPP4 Inhibitors MOA
Same effects as GLP1-RA but less overall clinical GLP-1 effects
Using DPP-4 Inhibitor and GLP1-RA together?
don’t use in combo
Dose adjustment with Renal insufficiency DPP4?
Sitaliptin = yes Linagliptin = don't need
DPP4 adverse effects?
well tolerated
Risk of pancreatitis = rare
** Saxagliptan associated with increase HF admissions, avoid in HF **
DPP4 disadvantages
costly
less effective compared to other agents
DPP4 are good to use in…
Frail or elderly persons that may not need significant A1c reduction or who have concern about Hypo risk, AE of other agents or unable to use injectable
SGLT2i Mechanism of Action
Blocks transporter of glucose in proximal tubule
** increase urinary glucose excretion **
Also has diuretic effect, slight BP drop/weight reduction
SGLT2i will have risk of….
Mycotic genital infections and UTI
Women more prone, men too
SGLT2i effect on reducing diabetes related chronic kidney disease?
All of them do it
also associated with reducing hospital admission rate due to HF.
Empagliflozin just got indication for HF
Dosing in renal insufficiency
Empagliflozin (Jardiance)
eGFR < 30 avoid use
HF pts < 20 no defined
Dosing in renal insufficiency
Dapagliflozin (Farxiga)
eGFR < 45 avoid use T2DM
All other indications eGFR < 25 avoid starting
Dosing in renal insufficiency
Canagliflozin (Invokana)
eGFR 30-59: lower dose to 100mg/day
eGFR < 30 avoid use
if already taking, eGFR <30 and UACR > 300 can continue 100mg/day
SGLT2i adverse effects
Polyuria = bathroom al ot Genital fungal infections UTI Monitor for volume depletion, hypotension DKA Amputations (Canagliflozin not others)
Sulfonylurea agents vs Glinide agents?
Sulfonylurea = longer acting, target other fasting and post prandial BG lvls
Glinide agents = primaire target post prandial BG levels, shorter acting
they target Beta cells
Adverse effects of Sulfonylurea and Glinides?
Hypoglycemia
Weight Gain
Dosing Sulfonylurea
once daily
BID at higher dosing to try to minimize hypoglycemia
Glinide Dosing (Repaglide)
start 0.5-1mg po TID 15min before each meal, skip med if skip meal
Increase dose every week as needed to max daily dose of 16mg
Can you still take Sulfonylurea agent if allergic to sulfa?
Generally yea, different moiety
Secondary failure
Good response at first, and then over time your response to these meds decreases
Sulfonylureas + Glinides
Who can benefit from Sulfonylureas + Glinides?
Thin body type
Newly diagnosed diabetes
Less significant Hyperglycemia
Glypizide to Glyburide dose?
Glipizide generally 2 times Glyburide (Max daily dose)
Glypizide vs Glyburide Metabolism?
Glyburide = metabolized in liver to active form, 50% renal elimination = longer hypoglycemia events
Glypizide = metabolized in liver to inactive form
Most important cautions with Sulfonylureas?
Have to take with food, or BG will go too low
Sulfonylurea and Meglitinide Agent counseling points?
Ensure you take with food
Getting Hypoglycemia episodes?
** If people fast, dose adjustment likely needs to happen…1/2 dose or skip dose depending on A1c**
Thiazolidinediones Mechanism of Action
Act on muscle level, improve insulin resistance and increase uptake into muscle
Use PPR-g
Takes 2-3 weeks for BG to start working due to protein turnover
How long can it take to see full effect of TZDs
can be seen in as little as 2-3weeks but can be up to 3-4 months
Place in therapy for TZDs
generally used as add-on oral therapy when patient refuses injections and accepts the side effect profile risk
Dosing Pioglitazone
start 15-30mg daily
increase dose every 3-4 weeks to a max of 45mg daily
no dose adjustment needed for renal insufficiency (not recommended due to fluid retention) and hepatic impairment
Pioglitazone side effects
Fluid retention and edema Weight gain Fracture risk Macular edema ** Black Box Warning for HF ** ** Contraindicated in Class 3/4 HF** caution in pt with Class 1/2 HF
Weird info Pioglitazone?
Possibility beneficial for NASH, animal models in liver cancer
induces ovulation = risk of getting preggers
Liver issues with TZDs?
should not be used in patients with active liver disease
monitor LFTs at baseline and periodically after
