Hypoglycaemic Agents

Question 1

Name the 2 insulin sensitizers:

Answer 1

1. Biguanide - Metformin
2. Thiazoldinediones - Pioglitazone

Question 2

Name the 2 Meglitinides.

Answer 2

1. Repaglinide
2. Nateglinide

Question 3

Name the 2 naturally occurring incretin hormones.

Answer 3

1. Glucose-dependent insulinotropic polypeptide (GIP)
2. Glucagon-like peptide-1

• increases insulin secretion when there is an increase in glucose levels

Question 4

Why do Incretin hormones have a short half life?

Answer 4

• due to rapid inactivation by dipeptidyl peptidase-4

(So in incretin based therapy, we inhibit dipeptidyl peptidase-4, so that incretin hormones will exist for longer and more insulin is secreted)

Question 5

Name the 3 SGLT2 inhibitors.

Answer 5

1. Empaglifozin
2. Canagliflozin (increases risk of lower limb amputation)
3. Dapaglifozin

Question 6

SGLT2 inhibitors have what effect?

Answer 6

• cardiorenal protective effects

Question 7

List out the 5 types of Hypoglycaemic Agents.

Answer 7

1. Insulin sensitisers
2. Insulin secretagogues
3. α glucosidase inhibitors
4. Incretin based therapy
5. Sodium-glucose co-transporter 2 inhibitors

Question 8

What are the 2 types of hypoglycaemic agents that cause weight gain?

Answer 8

1. Thiazoldinediones - Pioglitazone
2. Sulfonylureas e.g. Gibenclamide

• better not give in obese patients

Question 9

Which Hypoglycaemic agents are preferred for obese patients?

Answer 9

1. GLP-1 receptor agonist
   - incretin mimic, promotes secretion of insulin + feeling of satiety
2. Sodium-Glucose co-transporter 2 inhibitors
   - prevents reabsorption of glucose, glucose gets excreted

Question 10

What is the main difference between sulfonylureas and meglitinides? + implications

Answer 10

Dependency on glucose levels

Sulfonylureas NOT dependent, Meglitinides DEPENDENT

Sulfonylureas have a higher risk for hypoglycaemia as it is not glucose dependent
Meglitinides diminish at low glucose concentrations => reduces risk of hypoglycaemia

Question 11

What are some negative side effects of incretin mimetics?

Answer 11

1. GIT issues: nausea, vomiting, diarrhea, indigestion
2. Use w caution in patient w renal problems.
   => contraindicated in patients w severe renal impairment
3. Increased risk of Vit B12 malabsorption => vit b12 deficiency, can worsen symptoms of neuropathy

TLDR: git, renal, vit b12

Question 12

Simply put, what do Sulfonylureas do?

Answer 12

• bind to potassium channel => cause insulin to be released whether or not glucose is present

Question 13

Side effects of Sulfonylureas?

Answer 13

1. Weight gain
2. High risk for hypoglycemia
   - esp in elderly n those w renal/hepatic impairment
   - renal impairment=> metabolism impaired=> sulfonylurea stays in system for longer

Question 14

Name all the Sulfonylurea drugs:

Answer 14

1. Gibenclamide
   - longest acting sulfonylurea, highest risk of hypoglycemia
   - 50% renal 50% faecal excretion
2. Glipizide
   - shortest duration of action
   - excreted in urine
3. Glimepiride (2nd gen)
4. Gliclazide
5. Tolbutamide (1st gen)

Question 15

What are insulin secretagouges and which are the 2 classes of insulin secretagouges?

Answer 15

Insulin secretagouges: gets pancreatic β-cells to secrete insulin

1. Sulfonylureas
   - independent of glucose levels => higher risk of hypoglycemia
   - side effect: weight gain
2. Meglitinides
   - dependent on glucose levels, diminishes at low glucose concentrations => reduced risk of hypoglycemia
   - more rapid onset + shorter duration than sulfonylureas

Question 16

Name the 3 DPP-4 inhibitors:

Answer 16

1. Sitagliptin
2. Vildagliptin
3. Linagliptin*
   - suitable for px w renal impairment!!
   -> no dose adjustment in patients w chronic kidney disease cuz it is excreted 80% thru faeces (other 2 are excreted via renal)

Question 17

Which DPP-4 inhibitor is suitable in patients w renal impairment?

Answer 17

Linagliptin
- no dose adjustment in patients w chronic kidney disease cuz it is excreted 80% thru faeces (other 2 are excreted via renal)

Question 18

What are the glucose-dependent hypoglycaemic drugs?

Answer 18

Glucose-dependent: works only in presence of hyperglycemia)
1. Incretin based therapy
- DPP-4 inhibitors (Sitagliptin, Vildagliptin, Linagliptin)
- GLP-1 receptor agonists (Exanatide, Liraglutide)
2. Meglitinides (insulin secretagouges)
- Nateglinide
- Repaglinide

Question 19

What do α-glucosidase inhibitors do? Mechanism of action?

Answer 19

TLDR: prevent absorption of glucose in intestine

Mechanism:
1. Reversibly inhibits α-glucosidase in intestinal brush borders
2. Slow down increase in glucose levels after a meal => inhibit postprandial hyperglycaemia
3. Bacteria breaks down remaining carbs
- α-glucosidase hydrolyse oligosaccharide to glucose & other sugars
- stronger affinity to α-glucosidase than carbs (inhibitor + α-glucosidase > carbs + α-glucosidase)

Question 20

Name the hypoglycaemic drugs that can be orally administered

Answer 20

All hypoglycaemic drugs except GLP-1 receptor agonists(subcutaneous injection).

Aka.
1. Biguanide - Metformin
2. Thiazoldinediones - Pioglitazone
3. Sulfonyureas
4. Meglitinides
5. α-glucosidase inhibitor
6. DPP-4 inhibitors
7. SGLT2 inhibitors

Question 21

Name the hypoglycaemic drug that blocks glucose reabsorption at the kidneys.

Answer 21

SGLT2 inhibitors

Sodium-Glucose Co-Transporter 2 inhibitors

Question 22

Mechanism of action for SGLT2 inhibitors?

Answer 22

1. Inhibits SGLT2
   - decreases reabsorption of filtered glucose
   - decreases renal threshold for glucose (cannot hold as much glucose => pee out)
2. Increases urinary glucose excretion

Question 23

What is unique adverse effect of Canagliflozin?

Answer 23

Increased risk of lower limb amputation

Question 24

Adverse effects of SGLT2 inhibitors?

Answer 24

1. Urinary tract infection (due to increased glucose in urine, which bacteria will feed on)
2. Increased urination (cuz water leaves w the glucose)
3. Female genital mycotic infections (fungal)
4. Diabetic ketoacidosis (even if blood glucose normal)
   +
5. Canagliflozin: increased risk of lower limb amputation

Question 25

Which hypoglycaemic drug is administered subcutaneously

Answer 25

Glucagon-like peptide-1 (GLP-1) receptor agonists E.g. Exenatide, Liraglutide

Question 26

Name a α-glucosidase inhibitor.

Answer 26

Acarbose

Question 27

Gibenclamide is also known as..

Answer 27

Glyburide

Question 28

Liraglutide is a..

Answer 28

Incretin mimic. GLP-1 receptor agonist

Question 29

Exenatide is a..

Answer 29

Incretin mimic. GLP-1 receptor agonist

Question 30

What is the 1st line hypoglycemic drug given during therapy?

Answer 30

Metformin

Question 31

What are the 2nd line hypoglycemic drugs given during therapy?

Answer 31

1. SGLT 2 inhibitors 2. Sulfonylureas - given when metformin is not enough (all 3 drugs are relatively cheap)

Question 32

Which drugs are contraindicated in px w renal impairment?

Answer 32

1. Metformin (biguanide) 2. Pioglitazone (thiazoldinediones)

Question 33

Which drugs are contraindicated in px w pancreatitis?

Answer 33

Incretin based therapy - DPP-4 inhibitors - GLP-1 agonists

Question 34

Which hypoglycemic drug cannot be given in px w inflammatory bowel syndrome?

Answer 34

Acarbose