Diabetic Medications

Question 1

Where and how do Sulfonylureas (insulin secretogogues) work? Medication example? Are they for DM1 or DM2?

What has similar MOA to Sulfonylureas?

Answer 1

They work on the pancreas by stimulating beta cells which release insulin in DM2 pts.

Medication examples: Chlorpropamide, Tolbutamide (-mide) are FIRST-GEN. Glyburide and Glipizide (-ride and -zide) are SECOND-GEN (more potent).

Meglitinides (-glinide) have same MOA, just better for post-prandial spike (rapid onset, short DOA)

Question 2

Where and how do Incretins work? Medication example?

Where and how do DPP-4 inhibitors work? Medication example?

Are GLP-1 meds and DPP-4 meds used together?

In what pt populations are DPP-4 inhibitors used?

Are these drugs safe? and are they used secondarily to something?

Answer 2

Example of Incretin is GLP-1 agonist “Exanatide / (-tide)” which works on the pancreatic beta cells which release insulin UPON food intake. The amount released in proportional to how much you eat. This agonist acts like our natural GLP-1.

DPP-4 inhibitor is also under this category.

Example of DPP-4 inhibitor are “-gliptins”. They work by inhibiting the breakdown of endogenous GLP-1 and thus increasing it’s half-life.

GLP-1 and DPP-4 meds are not usually used together bc it doesn’t show much benefit and amps up cost for pt.

• Patients who can’t tolerate GLP-1 receptor agonists.
• Those preferring oral medications over injectables.
• Elderly or frail individuals with mild hyperglycemia.
• People with moderate kidney disease requiring safe options.

These drugs are relatively safe and commonly used secondarily to metformin.

Question 3

What are SGLT-2 inhibitors and how are they used? Medication example?

Major side effect/risk? Mechanism? Which population is more at risk?

Answer 3

SGLT-2 inhibitors work on the kidneys and promote the loss of glucose at the PT.

Medication example is canaglifozin.

A rare, but major risk of SGLT-2 inhibitors is euglycemic DKA. SGLT-2 inhibitors lower BG, pt then takes lower insulin dose, the drop in BG makes the body think its going towards hypoglycemia, glucagon is released which also strongly promotes lipolysis leading to ketones in the blood.

Type 1 diabetics are more at risk with off-label use.

Question 4

What are thiazolidinediones (TZD, -glitazones) and how are they used? Does it have any relationship with insulin resistance? Medication example?

Answer 4

TZDs work on increasing gene expression of GLUT transporter at the cellular level in tissues that are insulin-sensitive (adipose tissue, skeletal muscle, and the liver).

TZDs help lower insulin resistance and increase sensitivity.

Medication example is rosiglitazone.

Question 5

What are biguinides and how are they used? Medication example?

Answer 5

Biguinides work by lowering glucose synthesis (gluconeogenesis) via the liver.

Medication example is Metformin.

Question 6

Tell me about Tirzepatide: class, use, ADRs

Answer 6

-tide so GLP-1 agonist AND GIP agonist (dual activity)

can be used to promote weight loss, the GIP agnist part helps with bone formation by inhibiting bone resorption via osteoclasts.

works at the GI level so GI ADRs: N/V/D, constipation, and muscle loss

Question 7

How does glucagon work?

Answer 7

Binds to liver receptor, increases cAMP, causes glycogenolysis and gluconeogenesis to raise BGL in emergency situations.

If pt cannot swallow, IV dextrose.

Question 8

How to tx DKA?

When correcting DKA, what’s a possible electrolyte disturbance?

Answer 8

IV insulin, fluids, electrolytes (potassium, bicarb, phosphate)

hypokalemia can happen bc insulin causes it to shift INTO the call away from bloodstream.

Question 9

What are some notable SEs of sulfonylureas?

Answer 9

hypoglycemia, GI disturbances, photosensitivity

Question 10

What are some notable SEs of FIRST-GEN sulfonylureas? (-mide)

Answer 10

DDIs, avoid alcohol d/t disulfiram rxn, hypoglycemic risk in elderly with chlorpropamide

given all this, we don’t really use anymore

Question 11

What are some notable SEs of meglitinides?

Answer 11

weight gain, DDI

Question 12

What are some notable SEs of Exenatide?

Answer 12

pancreatitis

Question 13

What are some notable SEs of alpha glucosidase inhibitors?

Answer 13

diarrhea, flactulence

Question 14

What are some notable SEs of DPP-4 inhibitors?

Answer 14

headache, nausea

Question 15

What are some notable SEs of biguinides (metformin)?

Answer 15

diarrhea!!!, lactic acidosis (bc lactic acid is not used by liver for gluconeogenesis and builds up)

Question 16

What are some notable SEs of TZDs?

Answer 16

edema, fluid retention (not great for HTN and HF pts)

Question 17

What are some notable SEs of SGLT-2 inhibitors (canagliflozin)?

Answer 17

ketoacidosis!!, HTN, dehydration, UTI, low bone density

Question 18

Describe T1DM, T2DM, T3DM, and T4DM

Answer 18

T1DM: autoimmune, cannot make insulin

T2DM: insulin resistance

T3DM: non-pathological, drug-induced

T4DM: gestational DM

Question 19

How do alpha glucosidase inhibitors work? Medication example?

Answer 19

Medication example is “Acarbose and Migitol,” they slow carbohydrate absorption in the gut.

They are NOT absorbed, but interfere with absorption. by staying in the gut and not crossing into the bloodstream.

Question 20

How do Pramlintide’s work? What’s unique about it?

Answer 20

Pramlintide is a pancreatic amalyin analog which suppresses glucagon secretion and slows gastric emptying.

It is used with mealtime insulin in a separate syringe to enhance insulin’s effects!

Question 21

which drugs have the highest risk for hypoglycemia?

which drugs have medium risk for hypoglycemia?

which drugs have the lowest risk for hypoglycemia?

Answer 21

HIGH: insulin and pramlintide (used with insulin AND suppresses glucagon, double whammy!)

MEDIUM: sulfonylureas and meglitinides

LOW: GLP-1, DPP-4, TZDs, SGLT2, Metformin