Diabetes

Question 1

Metformin mechanism of action

Answer 1

1. Increase peripheral glucose uptake
2. Decrease hepatic glucose production
3. Decrease glucose absorption in GI tract

Question 2

Metformin pros/cons

Answer 2

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

Question 3

Metformin lactic acidosis risk factors

Answer 3

Contraindications:

• GFR<30
• Liver disease
• Alcohol use disorder
• Acute or exacerbated HF
• Past hx of lactic acidosis with metformin
• Hemodynamic instability

Question 4

GLP-1 Hormone Mechanism of Action

Answer 4

• Increases insulin secretion
• Decreases glucagon production
• Increases beta cell mass
• Increase satiety
• Increases insulin sensitivity

Question 5

DPP-4 Enzyme

Answer 5

Breaks down active incretins

Incretins are responsible for increasing the release of insulin and decreasing hepatic glucose production

Question 6

GLP-1 Agonists Mechanism of Action and Examples

Answer 6

Bind with GLP-1 receptor enhancing the effects of GLP-1

Mimic incretins

Examples: Liraglutide (Victoza), Dulaglutide (Trulicity), Semaglutide (Ozempic), Exenatide (Byetta), Lixisenatide (Adlyxin)

Question 7

GLP-1 Agonist Benefits

Answer 7

Reduces fasting and postprandial blood sugars

Weight loss

May decrease CVD outcomes

Can be given as monotherapy or as secondline agent

Question 8

GLP-1 Agonist Adverse Effects

Answer 8

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***

Question 9

DPP-4 Inhibitors Mechanism of Action and Examples

Answer 9

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)

Question 10

DPP-4 Inhibitor Benefits

Answer 10

Reduces fasting and postprandial blood sugar

No impact on weight

Low risk for hypoglycemia

Oral formulation

Question 11

DPP-4 Inhibitor Adverse Effects

Answer 11

URI, headache

Requires renal dosing

Avoid in HF patients

Question 12

SGLT2 Inhibitors: Mechanism of Action and Examples

Answer 12

Block reabsorption of glucose in the kidneys promoting renal excretion of glucose

Examples: Canagliflozin (Invokana), Empagliflozin (Jardiance), Dapagliflozin (Farxiga), Ertugliflozin

Question 13

SGLT2 Inhibitor Benefits

Answer 13

Weight loss

Decreased CVD outcomes

Low risk for hypoglycemia

Oral administration

Question 14

SGLT2 Inhibitor Adverse Effects

Answer 14

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.

Question 15

Thiazolidinediones Mechanism of Action and Examples

Answer 15

Diminish insulin resistance by increasing glucose uptake and metabolism in muscle and adipose tissues. Also decreases hepatic gluconeogenesis.

Examples: Pioglitazone, Rosiglitazone, Avandia

Question 16

Thiazolidinedione Benefits

Answer 16

Reduces fasting and postprandial blood glucose

Decreases lipids

Low risk for hypoglycemia

Oral administration

Question 17

Thiazolidinedione Adverse Effects

Answer 17

Weight gain, edema, anemia

Increased risk for fracture, ?? bladder cancer

Avoid with hepatic impairment

***Black Box warning: Avoid in HF class III or IV***

Question 18

Sulfonylureas Mechanism of Action and Examples

Answer 18

Stimulate first-phase insulin secretion in the pancreatic beta cells

Examples: Chlorpropamide (Diabinese), Tolbutamide (Orinase), Glipizide (Glucotrol), Glyburide (Diabeta), Glimepiride (Amaryl)

Question 19

Sulfonylureas Benefits

Answer 19

Lowers postprandial blood sugar

Oral administration

Inexpensive

Question 20

Sulfonylureas Adverse Effects

Answer 20

High risk for hypoglycemia (especially in CKD), weight gain, nausea, skin reaction, disulfarim like reaction

Interacts with many drugs (risk for hypo/hyperglycemia)

Question 21

Insulin onsets, peaks and durations

Answer 21

Question 22

Basal Insulin

Answer 22

Controls fasting blood sugars

Weight based dosing to start 0.1-0.2u/kg

Titrate every 2-3 days to reach glycemic goal

Question 23

Signs of “overbasalization” with insulin therapy

Answer 23

• 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

Question 24

Prandial Insulin

Answer 24

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