EXAM 4 Diabetes Drugs Dr. Hess Flashcards
What is the backbone of treating Prediabetes and T2DM?
-Medical nutrition therapy -> individualized meals (dietitian) -> weight loss
-Exercise
MOA of Metformin
Insulin Sensitizer (reducing Insulin resistance)
-reduces hepatic glucose production and glucose absorption in the gut
What is the most common side effect of Metformin?
Diarrhea
-it reduces glucose absorption in the gut -> glucose stays in the gut where bacteria comes in
What are ways to reduce the adverse effects of diarrhea when taking Metformin?
-take with food
-titrate weekly (increase by 500 mg)
-use the ER formulation
What is the maximum dose of Metformin?
2550 mg/day (850mg TID)
the maximum dose that is actually effective and seen in practice is 2000 mg
-titrate up until 2000 mg or control of blood glucose
-if blood glucose is controlled then don’t need to go to 2000 mg and potentially cause diarrhea (dose-depndent)
How much does Metformin lower A1c?
on average 1-2%
(reducing A1c by more than 1% is considered high efficacy)
What is the risk of Hypoglycemia of Metformin?
Low
-since it doesn’t stimulate insulin release but increases sensitivity
How does Metformin affect weight?
weight-neutral
Contraindications of Metformin
-Renal disease (eGFR < 30)
->excreted 100% in the kidney
-use of contrast dye - nephrotoxic (eGFR < 60)
-BBW: Lactic acidosis (don’t give if hx of Lactic acidosis)
-reduces Vitamin B12 absorption
A patient’s eGFR on Metformin has decreased to 35, what is the medical approach to it?
eGFR: 30-45
-if they were not on Metformin don’t start
-if they are on Metformin: consider a 50% dose reduction and close monitoring
if the eGFR is below 30: CONTRAINDICATED
if eGFR is over 45: it is OK to start or continue
MOA of SGLT2i
blocking glucose reabsorption in the kidney
-> excreted via urine
Efficacy of SGLT2i
0.5 - 1% (moderate)
What are the other protective effects of SGLT2i?
-Cardiovascular protective (heart failure)
-Renal protective (CKD)
Hypoglycemia risk for SGT2i
Low
Adverse effects of SGLT2i
Mycotic infections, UTI
-Polyuria
-dehydration (mild diuretic)
-Hypotension
-Weight loss !!!
-Euglycemic diabetic ketoacidosis (rare)
Why may patients on SGLT2i develop Euglycemic diabetic ketoacidosis?
the blood glucose is normal (normal-high) but they are acidic
they pee out the sugar which lowers the blood glucose
When are SGLT2i contraindicated?
severe renal dysfunction (eGFR < 20)
Which SGLT2i is indicated for T2DM with ASCVD, HF, and CKD?
Jardiance (Empagliflozin)
What is the indication of Farxiga (dapagliflozin)?
T2DM
HF
CKD
What is the indication of Invokana (Canagliflozin)?
T2DM
T2DM with ASCVD
T2DM with CKD
had a BBW for imputations, but it was removed
-not often used in practice
What is the risk of hypoglycemia for SGLT2i when combined with other antidiabetics?
-SGLT2i has a low risk of hypoglycemia
-SU has a higher risk of hypoglycemia -> combined higher risk for hypoglycemia
reduce the dose of SU to reduce the risk of hypoglycemia
Which SGLT2is have shown renal benefits?
Farxiga (dapagliflozin)
Invokana (canagliflozin)
Which of the SGLT2i have HF benefits?
Farxiga (dapagliflozin)
Jardiance (empagliflozin)
Which of the SGLT2i have CVD benefits?
Jardiance (empagliflozin)
Invokana (canagliflozin)
Which drugs may cause weight loss?
SGLT2i (pee out 80g sugar per day)
GLP-1
..
MOA of GLP-1 and GIP
activate GLP-1 receptors -> increase in insulin secretion (endegeounous GLP-1 comes from the gut)
high efficacy: 0-75 - 1.5%
How does GLP-1 cause weight loss?
it works in different parts of the body:
Brain: reduced food intake, increased satiety
Pancreas: GLP-1: increased insulin, decreased glucagon
Stomach: reduced gastric emptying
Why does GLP-1 have a low hypoglycemia risk despite increasing insulin release?
Because the insulin release is glucose-dependent
What are the side effects of GLP-1?
-N/VD
-Weight loss
-Pancreatitis (rare)
-Injection reactions
What is the BBW for GLP-1?
-Hx of medullary thyroid carcinoma (MTC) seen in rats
-not thyroids, but medullary thyroid cancer -> produces calcitonin
-Hx of multiple endocrine neoplasm type 2 (MEN2)
Patient population to be cautious when using GLP-1?
-poor renal function (should be over 30)
-when they use Sulfonylurea -> hypoglycemia risk
-Hx pancreatitits
-Hx of gastroparesis or delayed gastric emptying
Which GLP-1s have an indication for T2DM with ASCVD?
Victoza
-Ozempic
-Trulicity (dulaglutide)
How are GLP-1 dosed?
weekly
except for Vicotza
How are SGLT2i dosed?
daily
start dosing -> uptitration
Which drug is a GIP and GLP-1 agonist?
Tirzepatide (Mounjaro)
How is Tirzepatide (Mounjaro) dosed?
increase in the dose every month by 2.5 mg (if they tolerate it)
it is taken once a week
Which GLP-1 has the longest/shortest storage time at room temperature?
longest: Ozempic (56 days)
shortest: Trulicity (14 days)
Which GLP-1s have a storage time at room temperature of 28-30 days?
Bydureon BCise (exenatide LA): 28 days
Byetta (exenatide): 30 days
Victoza (Liraglutide): 30 days
all of them including Ozempic, Trulicity and Mounjaro should be kept in the fridge prior using
What is the orally formulated GLP-1 and how should it be taken?
Semaglutide (Rybelsus)
-at least 30 minutes before the first food, beverage, or other oral medications
-not more than 4 oz water
-Keep in the original blister pack (protection from moisture)
Which of the GLP-1s have CVD benefits?
-Victoza (Trulicity)
-Ozempic (Semaglutide)
-Trulicity (Dulaglutide)
What is the first-line antidiabetic drug based on the guidelines?
if they have ASCVD risk, HF, or CKD
-> go with SGLT2i or GLP-1 before metformin
in practice, Metformin is often used first
