Diabetes Flashcards
Metformin mechanism of action
- Increase peripheral glucose uptake
- Decrease hepatic glucose production
- Decrease glucose absorption in GI tract
Metformin pros/cons
Pros:
- Effective at lowering glucose levels and A1C
- Low risk for hypoglycemia
- Weight loss
- Lowers lipid levels
Cons:
- GI upset
- B12 deficiency with prolonged use (anemia)
- Lactic acidosis
Metformin lactic acidosis risk factors
Contraindications:
- GFR<30
- Liver disease
- Alcohol use disorder
- Acute or exacerbated HF
- Past hx of lactic acidosis with metformin
- Hemodynamic instability
GLP-1 Hormone Mechanism of Action
- Increases insulin secretion
- Decreases glucagon production
- Increases beta cell mass
- Increase satiety
- Increases insulin sensitivity
DPP-4 Enzyme
Breaks down active incretins
Incretins are responsible for increasing the release of insulin and decreasing hepatic glucose production
GLP-1 Agonists Mechanism of Action and Examples
Bind with GLP-1 receptor enhancing the effects of GLP-1
Mimic incretins
Examples: Liraglutide (Victoza), Dulaglutide (Trulicity), Semaglutide (Ozempic), Exenatide (Byetta), Lixisenatide (Adlyxin)
GLP-1 Agonist Benefits
Reduces fasting and postprandial blood sugars
Weight loss
May decrease CVD outcomes
Can be given as monotherapy or as secondline agent
GLP-1 Agonist Adverse Effects
N/v/d, acute pancreatitis
Increased risk for hypoglycemia when used in combination with sulfonylureas and insulin
Do NOT use with DPP4 inhibitor
Use caution with renal impairment
***Black box warning: Risk for thyroid cancer***
DPP-4 Inhibitors Mechanism of Action and Examples
Inhibit the breakdown of GLP-1 by inhibiting the action of DPP4 - an enzyme that breaks down GLP1
Examples: Sitagliptin (Januvia), Saxagliptin (Onglyza), Linagliptin (Tradjenta), Alogliptin (Vipidia/Nesina)
DPP-4 Inhibitor Benefits
Reduces fasting and postprandial blood sugar
No impact on weight
Low risk for hypoglycemia
Oral formulation
DPP-4 Inhibitor Adverse Effects
URI, headache
Requires renal dosing
Avoid in HF patients
SGLT2 Inhibitors: Mechanism of Action and Examples
Block reabsorption of glucose in the kidneys promoting renal excretion of glucose
Examples: Canagliflozin (Invokana), Empagliflozin (Jardiance), Dapagliflozin (Farxiga), Ertugliflozin
SGLT2 Inhibitor Benefits
Weight loss
Decreased CVD outcomes
Low risk for hypoglycemia
Oral administration
SGLT2 Inhibitor Adverse Effects
Frequent UTI and yeast infections (think sugar in the urine)
Risk for amputation
Risk for dehydration and DKA
Decreasing effect with lowered kidney function, avoid if GFR<45. Check renal function prior to intiating.
Thiazolidinediones Mechanism of Action and Examples
Diminish insulin resistance by increasing glucose uptake and metabolism in muscle and adipose tissues. Also decreases hepatic gluconeogenesis.
Examples: Pioglitazone, Rosiglitazone, Avandia
Thiazolidinedione Benefits
Reduces fasting and postprandial blood glucose
Decreases lipids
Low risk for hypoglycemia
Oral administration
Thiazolidinedione Adverse Effects
Weight gain, edema, anemia
Increased risk for fracture, ?? bladder cancer
Avoid with hepatic impairment
***Black Box warning: Avoid in HF class III or IV***
Sulfonylureas Mechanism of Action and Examples
Stimulate first-phase insulin secretion in the pancreatic beta cells
Examples: Chlorpropamide (Diabinese), Tolbutamide (Orinase), Glipizide (Glucotrol), Glyburide (Diabeta), Glimepiride (Amaryl)
Sulfonylureas Benefits
Lowers postprandial blood sugar
Oral administration
Inexpensive
Sulfonylureas Adverse Effects
High risk for hypoglycemia (especially in CKD), weight gain, nausea, skin reaction, disulfarim like reaction
Interacts with many drugs (risk for hypo/hyperglycemia)
Insulin onsets, peaks and durations
Basal Insulin
Controls fasting blood sugars
Weight based dosing to start 0.1-0.2u/kg
Titrate every 2-3 days to reach glycemic goal
Signs of “overbasalization” with insulin therapy
- basal dose greater than ∼0.5 units/kg,
- high bedtime blood glucose minus morning or post-preprandial glucose differential
- (e.g., bedtime-morning glucose differential ≥50 mg/dL),
- hypoglycemia (aware or unaware),
- high variability in blood sugars
- If fasting sugars are good but A1c is high then check post prandial sugars
Prandial Insulin
Controls post-prandial blood sugars
Rapid/short acting (often Regular Insulin)
Initiation of prandial insulin
•Start with 4 units or 10% of the amount of basal insulin at the largest meal or the meal with the greatest postprandial excursion
As prandial insulin is adjusted it may make sense to decrease basal insulin dosing
