"Older" Non-insulin Analogues Flashcards
List the 5 “older” options for non-insulin analogues.
- Biguanides
- Sulfonylurea
- Meglitinides
- Thiazolidinediones
- Alpha-glucosidase inhibitors
What is the main biguanide used? What’s the MOA?
Metformin
MOA:
- decrease hepatic glucose production
- increase secretion of GLP-1
may also:
- decrease intestinal absorption of glucose
- increase peripheral glucose uptake
What are the three indications for using biguanides (Metformin)?
- Prediabetes
- T2DM (1st line - every pt should be on metformin as long as no C.I.)
- monotherapy
- combotherapy - Insulin resistance in PCOS pt
When should you use metformin in a prediabetic?
A1c 5.7-6.4 or FBG 100-125
especially:
- < 60yo
- BMI > 35
- h/o gestational DM
How would you dose a patient for metformin?
Start: 250-500 mg/d
Titrate by 250-500mg q1-2wk as tolerated
Usual effective dose = 2g**
Do NOT titrate too fast and scare patient away with ADRs.
What are three clinical pearls related to Metformin?
- RARELY causes hypoglycemia
- Associated w/decreased micro/macrovascular complications (mostly micro)
- Lipid lowering activity
- decrease TG, FFA, LDL
- increase HDL
What are the two things you should monitor for patient on metformin?
- H/H & RBC indices
- beware of B12 def
- monitor initially & at least annually - eGFR
- baseline & at least annually
Which comorbidity has Metformin been proven safe in? Which comorbidity should you avoid Metformin in?
Safe: Stable HF
- hold during exacerbation
Avoid: Renal dysf (GFR <30)
- decreased clearance of lactate –> increased risk for lactic acidosis
Monitor eGFR with your metformin patient. What do you need to know about the values?
> 60: no real concerns
45-60: continue dose, routine f/u
30-45: do NOT initiate therapy at this stage
- continue if already on, should reduce dose 1/2 for CKD
< 30: do NOT use**
What are the Pk and Pd for metformin?
Pk: no CYP interactions (not metabolized)
Pd:
- concomitant hypoglycemic agent
- hyperglycemic-inducing agent (counteracts)
What do you need to do with metformin if your patient is having a radiologic procedure involving IV iodinated contrast?
D/c immediately prior to & for 48hr
Contrast may cause AKI w/increase risk of lactic acidosis
What are 3 ADRs of metformin?
- GI intolerance (MC)
- Metallic taste*, mild anorexia, NVD, abd discomfort - Macrocytic anemia & peripheral neuropathy
- Lactic acidosis
- more serious LA accumulation occurs w/conditions leading to hypoxemia (e.g. AKI or CKD)
Metformin may decrease Vit B12 absorption. Who should you check [B12] and what do you recommend your patient?
Check [B12]
- new or worsening peripheral neuropathy or macrocytic anemia
- at risk pt (vegetarian, PPI user, elderly)
Recommend: daily complete multivitamin for all pt on metformin**
What are the three 2nd gen sulfonylurea? Which is generally the best option to use?
- glyburide (not recommended in ANYONE)
- glimepiride (not recommended in ELDERLY)
- glipizide **
- generally best option to use
What are the sulfonylurea MOA?
Stimulate insulin secretion
Sulfonylurea binds to pancreatic beta cell and insulin is released.
What is the half life of ‘regular’ glipizide? How do you dose it?
2-5 hours
BID dosing
- typically started w/low dose before breakfast
What are the clinical indications of Sulfonylureas?
T2DM
- monotherapy
- combination therapy
Falling out of favor.
What are clinical pearls of metformin?
- decrease A1c 1-1.5%
- needs insulin to work**
- promotes modest weight reduction or at least weight stabilization
Name 3 clinical pearls regarding Sulfonylureas?
- decrease A1c 1-1.5%
- promotes wt gain**
- Glyburide C.I. for eGFR < 50 and also has an active metabolite **
What allergic reaction may occur with Sulfonylurea use?
“Sulfonamide” allergy**
What is the Pk and Pd related to Sulfonylureas?
Pk: 2C9 substrates
Pd:
- concomitant hypoglycemia agent
- hyperglycemia-inducing agent
What are the two most common ADRs related to Sulfonylureas?
**Wt gain & hypoglycemia (glyburide > glimepiride > glipizide)
No CV harm, but No CV benefit either
After metronidazole, what is the next drug you should think of for “disulfiram-like reaction”? Especially after ETOH ingestion.
Glyburide
What are the two Meglitinides? What is the MOA of Meg Zoooot?
Nateglinide & Repaglinide
MOA: increase insulin secretion
- structurally different and exert effects via different receptors compared to sulfonylureas
What are the clinical indications for Meglitinides?
T2DM
- monotherapy
- combo therapy
What should you know regarding the dosing of Meglitinides?
- take prior to meal (e.g. TID)
- dose should be skipped if meal is missed**
Meglitinide clinical pearls?
- A1c reduction 0.5-1%
- weight neutral
- no micro/macrovascular data
main role: “be a sulfonylurea for CKD pt –> mostly repaglinide” **
What is the one ADR related to Meglitinides?
MC is hypoglycemia
less than Sulfonylureas?
What are the two Thiazolidinediones (TZDs)? MOA?
- Pioglitazone > `rosiglitazone
- MOA: increased insulin sensitivity by acting on adipose, muscle, and liver to increase glucose utilization and decrease glucose production
TZD indications
- Don’t use unless forced to!
- Monotherapy DMII or combo
- Insulin resistance in PCOS (metformin first)
TZD Pearls
- Dec A1c 1-1.5%, no hypoglycemia
- **Does not inc pancreatic secretion–> needs insulin
- **May take 6-14 wks for max effect
- **Don’t use in pts who have/had bladder CA
TZD warnings/ADR
- CI in pts w/ NYHA III/IV
- BBW for inc risk of angina or AMI, removed in 2014
- LFT monitoring
- Weight gain, **fluid retention
- **dec bone dens, inc fracture risk
What are the alpha-glucosidase inhibitors? MOA?
- Acarbose, Miglitol
- MOA: Interfere with hydrolysis of carbs in SI, delay absorption of glucose
Alpha-glucosidase indications
- Monotherapy or combo
- Dose TID and take before meals
Alpha-glucosidase Pearls
- No hypoglycemia, dec A1c 0.5-1.0%
- **CI in pts with intestinal or bowel dz, intestinal obstruction
Alpha-glucosidase Pearls
- Abd pain, diarrhea, rancid farts
- **Pts often d/c med due to this
- Begin with lose dose and titrate up to avoid
