Endocrine 3 (Type 2 Diabetes | Non Cardio Risk)

Question 1

Sodium Glucose Cotransporter 2 Inhibitors
(SGLT2)
- Examples

Answer 1

Canagliflozin, Dapagliflozin, Empagliflozin, Ertugliflozin, Bexagliflozin

Question 2

Sodium Glucose Cotransporter 2 Inhibitors
(SGLT2)
- MOA

Answer 2

Inhibits SGLT2
- Preventing reabsorption of glucose
- Lowers Blood Sugar

Question 3

Sodium Glucose Cotransporter 2 Inhibitors
(SGLT2)
- Benefits

Answer 3

Benefits
- No Insulin Action = No Hypoglycemia
- Benefits Cardiovascular System

Question 4

Sodium Glucose Cotransporter 2 Inhibitors
(SGLT2)
- Adverse Effects

Answer 4

Adverse
- Increase Urinary/Genital Infection
- Increases Ketoacidosis (Greater concern in Type 1)
- Increased Risk of Amputation (Canagliflozin)

Question 5

Incretin Effect

Answer 5

Oral Administered Insulin will trigger endocrine receptors leading to the secretion of hormones on its way to the pancreas
- Results in a larger response

Question 6

GLP-1
- MOA

Answer 6

Enhances glucose stimulated insulin secretion
- More potent at higher levels of glucose

Low risk of hypoglycemia as it is glucose dependent
- Less Glucose = Less Insulin

Inhibits Glucagon secretion
- Decreases Hepatic Glucose Production

Inhibits Gastric Emptying
- Delays appearance of nutrients like glucose in the circulation

Inhibits Appetite
- Reduction in body weight and adiposity

Must be injected

Question 7

GLP-1
- Benefits

Answer 7

Benefits:
- Weight Loss
- No Hypoglycemia
- Reduced cardiovascular risks

Question 8

GLP-1
- Adverse Effects

Answer 8

Adverse:
- Increased Heart Rate
- Pancreatitis (No data, however, still some concerns)

Question 9

How is inactivation of GLP-1 prevented

Answer 9

Dipeptidyl-Peptidase 4 (DPP-4) is an enzyme that inactivates GLP-1

Prevent inactivation by:
- Degradation-Resistant GLP-1R Agonists
- DPP-4 Inhibitors

Question 10

DPP-4 Inhibitor
- Example

Answer 10

Sitagliptin, Vildagliptin, Saxagliptin, Alogliptin, Linagliptin

Question 11

DPP-4 Inhibitor
- MOA

Answer 11

Inhibits DPP-4 to prevent the breakdown of endogenous GLP-1

Taken Orally

Question 12

DPP-4 Inhibitor
- Benefits

Answer 12

Benefits:
- No Hypoglycemia

Question 13

DPP-4 Inhibitor
- Adverse Effects

Answer 13

Adverse:
- Pancreatitis (No data)
- Does not cause weight loss like GLP-1 agonists
- Increased risk of heart failure (Saxagliptin)

Question 14

GLP-1 Agonists vs DPP-4 Inhibitors

Answer 14

Both induce glucose-lowering by manipulating GLP-1 action on insulin secretion
- GLP-1 agonists have a larger effect as they are a new stimulation (Pharmacological)
- DPP-4 Inhibitors only affect endogenous GLP-1 (Physiological)
- DPP-4 degrades a large number of peptides, a very complex process