PR2157 Diabetes

Major drugs for T2DM

What is the MOA of Metformin?

1. Reduce gluconeogenesis in the liver

2. Increase peripheral uptake of glucose mainly in skeletal muscles by increasing insulin sensitivity

What drug class is metformin?

biguanides

What are the adverse effects of metformin?

Anorexia, GI disturbances, increased risk of VitB12 malabsorption, use with caution in patients with renal impairment or lactic acidosis

What is lactic acidosis?

1. increased production of lactate due to lack of oxygen (anaerobic respiration, from pyruvate)

2. decreased clearance of lactate due to liver impairment

What are the possible drug interactions with Metformin?

1. alcohol (increase risk of lactic acidosis)

2. Organic cationic transporter 2 inhibitors may increase the plasma metformin by reducing renal elimination of the drug

What is the drug class of Glipizide?

Sulfonylureas

What is the MOA of sulfonylureas?

Insulin secretagogues

1. Binds to the subunits of the ATP-sensitive Katp channels

2. Inhibits the K efflux

3. triggers the calcium-dependent exocytosis of insulin from pancreatic beta cells (to secrete insulin)

What is an important factor for sulfonylurea drugs to work?

Functional pancreatic beta cells

What are the adverse effects of Sulfonylureas?

1. Hypoglycemia (more common in elderly)

2. Weight gain

What are the possible drug interactions with sulfonylureas? (There is 3)

1. Beta blockers may worsen the signs and symptoms of hypoglycemia

2. Disulfiram-like reaction with alcohol (flushing, tachycardia, vomitting, “drunk”)

3. CYP2C9 inhibitors may increase the presence of glipizide, glimepiride

What drug class is repaglinide?

Meglitinide analogue

What is the MOA of repaglinide/ Meglitinide analogues?

Same as sulfonylureas but less potent

1. Bind to the subunits of ATP-sensitive Katp channels

2. inhibits K efflux

3. Triggers calcium-dependent exocytosis of insulin (secrete insulin)

Should Repaglinide be used in tandem with Sulfonylureas?

NOOOOOO

What are some drug interactions with Meglitinide analogues?

1. taking it together with NPH insulin has reported to cause MI

2. taking it together with fibric acid derivatives may increase hypoglycemia (CYP2C8)

What drug class is Empagliflozin?

SGLT-2 inhibitors

What is the MOA of SGLT-2 inhibitors?

Inhibit sodium-glucose co-transporter-2

1. decrease reabsorption of filtered glucose

2. decrease threshold for glucose

3. increase glucose excretion via urine

Empagliflozin/ SGLT-2 inhibitors can be used together with metformin for a more therapeutic effect. True/ False?

True

What are some adverse effects of SGLT-2 inhibitors? (5)

1. UTI

2. increased urination

3. female genital mycotic infection/ fungal infection

4. diabetic ketoacidosis

5. fournier gangrene

What are incretins?

Metabolic hormones released after eating in glucose-dependent manner

they augment secretion of insulin released from pancreatic beta cells ONLY in the presence of hyperglycemia

Which organ secrets incretins?

Small intestine

What are the two types of incretin hormones released?

GIP and GLP-1

What is the drug class of Sitagliptin?

Dipeptidylpeptidase-4-inhibitor (DPP-4 inhibitor)

What is the MOA of DPP-4 inhibitors?

1. Binds and inhibits the DPP-4 enzyme

2. decrease enzymatic degradation of endogenous incretins

3. Prolongs the actions of endogenous incretin hormones

What are the adverse effects of DPP-4 inhibitors?

1. flu-like symptoms

2. arthralgia

3. dermatologic reactions

4. acute pancreatitis

What drug class is semaglutide?

GLP-1 agonist

What is the MOA of GLP-1 agonist?

1. Bind to GLP-1 receptors on beta cells

2. activates adenylate cyclase

3. activates cAMP and increases the protein kinase A signalling

4. increases glucose-dependent insulin secretion

5. decreases glucagon secretion from alpha cells

6. decreases hepatic glucose production

What are the additional effects of GLP-1 agonists on the body?

1. slows gastric emptying

2. increases satiety

3. reduced food intake

What are the adverse effects of GLP-1 agonists?

1. GI tract (nausea, vomiting, abdominal pain (improves when body adjusts to treatment)

2. diarrhoea, constipation

3. headache/ fatigue

4. alopecia (associated with rapid hairloss)

5. acute pancreatitis

6. acute gallbladder disease

7. worsening pre-existing diabetic retinopathy

What are some drug interactions with GLP-1 agonists?

Due to the additional effect on the body like slower gastric emptying, may affect the absorption of concomitant oral medications.

Which drug increases the risk of aspiration during procedures requiring general anesthesia or deep sedation?

GLP-1 agonists