Diabetes (Slide Deck 4) Flashcards
What does metformin do?
- ↓’s hepatic glucose production
- Can also enhance sensitivity to insulin
- Increases glucose utilization via action in the gut
- Has effects on the gut microbiome which may explain some anti- inflammatory effects
What is the typical dose of metformin?
Start at 250-500 then work to 850-1000mg (Titrating dose decreases the side effect profile)
By how much does the A1C decrease typically decrease on Metformin?
1-1.5%
What is a common AE with metformin?
Diarrhea and GI discomfort
How can the side effects of metformin be avoided?
Titrating doses, Take with food, Extended release version
What are the precautions when taking metformin?
Lactic Acidosis which decreases arterial PH and accumulation of serum lactate
What ClCr is used for metformin decrease
Less then 60ml/min
45-59=1500mg/day
30-44 1000mg/day
What happens if someoen has a ClCr of <30ml/min and is on metformin
Can continue 500mg OD but should not start but can continue the dose
What is the MOA of Sulfonylureas
Enhance insulin secretion by binding to Su receptors on beta cells of the pancreas
This leads to K+ closing and opening of CC stimulating insulin secretion
What are the three 2nd generation sulfonylureas?
glyburide, gliclazide, glimepiride
How much A1C decrease do we see with Sulfonylureas usage?
1-1.5%
What are the adverse effects of Sulfonylureas usage?
Hypoglycemia and weight gain
Which of the sulfonylureas can you use during pregnancy?
glyburide
Which contraindications are present for sulfonylureas?
CI in hepatic and renal impairment
Hold in acute ilness
What are some common DI with sulfonylureas?
Sulfonamides
Alcohol
What is the MOA of Meglitinides?
Binds to a site adjacent to the SU receptor, resulting in stimulation of the secretion of insulin from the pancreas
Similar to SUs but have a faster onset and shorter D of A * Peak levels within 1 hour and half-life is 1 hour
What is the medication that falls under meglitinides?
Repaglinide
How much A1C decrease does repaglinide cause?
1 to 1.5
What adverse effects are associated with repaglinide?
Hypoglycemia and weight gain
What precautions must be taken when on repaglinide?
Cyp 3A4 inhibitors (Increases concentration) grapefruit juice is the biggest one
Alpha-Glucosidase Inhibitors MOA?
- α-Glucosidase enzymes in the small intestine are responsible for the breakdown of polysaccharides into absorbable glucose
- Acarbose inhibits these enzymes, hence there is a delay in the rate of digestion of CHO’s and glucose absorption
Net effect is reduction in PPG levels
What level of A1C decreasing doe we see on Alpha-Glucosidase Inhibitors?
0.5%-0.8%
What is a common Alpha-Glucosidase Inhibitors
Acarbose
What are some adverse effects of Acarbose?
GI Flatulence and diarrhea
What is cautioned with taking acarbose?
IBD and Gi conditions
eGFR <25ml/min and severe liver disease
What is a common Alpha-Glucosidase Inhibitors?
Acarbose
What is a common Alpha-Glucosidase Inhibitors?
Acarbose
What are the thiazolidinediones drugs
Rosiglitazone and Pioglitazone
What are the MOA thiazolidinediones drugs
Bind to PPAR-γ receptors which are primarily found in adipose tissue. Activation alters genes that influence glucose and lipid metabolism.
Which enhances insulin sensitivity at muscle liver and fat tissues
What are the clinical effects of Thiazolidiendiones
Enhance insulin sensitivity at muscle, liver, and fat tissues.
Decrease insulin resistance
Decrease hepatic glucose production
What is the typical decrease in A1C level when on Thiazolidinediones?
1-1.5%
What are the adverse effects of Thiazolidinediones
Peripheral edema (~5%); combined with insulin (~15%)
Weight gain
New onset of worsening of HF
Increase in distal fractures in postmenopausal women
What is the concern with TZDs and what did it cause?
Cardiovascular Effects,
Hence all new Diabetes drugs require cardiovascular trials to back it up
What are the Incretin Based therapies targets?
GLP-1 DPP4 and GIP
What are the GLP-1 receptor agonists drugs
- Exenatide (Byetta®)
- Liraglutide (Victoza®) ®
- Dulaglutide (Trulicity®)
- Exenatide weekly (Bydureon®)
- Lixisenatide (Adlyxine®)
- Semaglutide (Ozempic® SC), and Rybelsus® oral)
What are the DPP-4 inhibitors?
- Linagliptin (Trajenta®)
- Sitagliptin (Januvia®)
- Saxagliptin (Onglyza®)
- Alogliptin (Nesina®)
What are the effects of activating GLP-1
Increase insulin secretion, decrease glucagon, slow gastric emptying and increase satiety
What does DPP-4i do?
Inhibits DPP-4 which stops the cleaving GLP-1
How much does DPP4 inhibitors decrease A1C?
0.7, but typically less then 1
What are some adverse effects and precautions of taking DPP4I
headaches Nasopharyngitis and URTI
Are DPP5 inhibitors CV safe?
yes! but not proven or shown to be cardioprotective
What are DPP4i typically good for?
Elderly and for individuals who do not have large A1C lowering targets
What is the GLP1RA MOA?
Stimulates insulin secretion in a glucose-dependent manner, decreases glucagon, slows gastric emptying, increases satiety
What is the GLP1RAs A1C lowering abilities
1-1.5%
What are the general AE of GLP1RA?
N/V/D, but will resolve in 4-8 weeks
Weight loss due to medication not N/V/D
What are the drug interactions of GLP1RA
Oral Contraceptives
Antibiotics
Narrow TI drugs
Levothyroxine
What renal measurement should Repaglinide be cautioned with?
<30ml/min
