30. Anti-Obesity & T2 Diabetes Therapies

Question 1

Define

Laproscopic sleeve gastrectomy (LSG)

Answer 1

a weight loss procedure where about 75% of the stomach is removed leaving a narrow gastric “tube” or “sleeve”

Question 2

Define

Sulfonylureas

Answer 2

a group of medicines used to treat type 2 diabetes. They act by increasing insulin release from the beta cells in the pancreas.

Question 3

Define

Orlistat

Answer 3

a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake

Question 4

Define

Lorcaserin

Answer 4

a weight-loss drug developed by Arena Pharmaceuticals. It reduces appetite by activating a type of serotonin receptor known as the 5-HT2C receptor in a region of the brain called the hypothalamus, which is known to control appetite

Question 5

Define

Contrave

Answer 5

a combination (naltrexone/bupropion) medication for chronic weight management. It is for people with overweight and weight-related complications or obesity. It is meant to be used together with a lifestyle therapy regimen involving a reduced calorie diet and increased physical activity

Question 6

Define

Laproscopic adjustable gastric band (LAGB)

Answer 6

a type of weight-loss surger where an inflatable silicone device placed around the top portion of the stomach to treat obesity, intended to decrease food consumption

Question 7

Define

Incretin

Answer 7

a group of metabolic hormones that stimulate a decrease in blood glucose levels

Question 8

Define

GLP-1 receptor agonists

Answer 8

a type of incretin-based medicine for type 2 diabetes. This type of medicine is based on the action of hormones called incretins, which help control how the pancreas works

Question 9

Define

Bariatric surgery

Answer 9

surgery that affects your stomach and how you digest food. It’s designed to make your stomach much smaller, which causes you to feel full after eating only a small amount of food

Question 10

Define

Metformin

Answer 10

marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is not associated with weight gain.

Question 11

Definition

a weight loss procedure where about 75% of the stomach is removed leaving a narrow gastric “tube” or “sleeve”

Answer 11

Laproscopic sleeve gastrectomy (LSG)

Question 12

Definition

a group of medicines used to treat type 2 diabetes. They act by increasing insulin release from the beta cells in the pancreas.

Answer 12

Sulfonylureas

Question 13

Definition

a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake

Answer 13

Orlistat

Question 14

Definition

a weight-loss drug developed by Arena Pharmaceuticals. It reduces appetite by activating a type of serotonin receptor known as the 5-HT2C receptor in a region of the brain called the hypothalamus, which is known to control appetite

Answer 14

Lorcaserin

Question 15

Definition

a combination (naltrexone/bupropion) medication for chronic weight management. It is for people with overweight and weight-related complications or obesity. It is meant to be used together with a lifestyle therapy regimen involving a reduced calorie diet and increased physical activity

Answer 15

Contrave

Question 16

Definition

a type of weight-loss surger where an inflatable silicone device placed around the top portion of the stomach to treat obesity, intended to decrease food consumption

Answer 16

Laproscopic adjustable gastric band (LAGB)

Question 17

Definition

a group of metabolic hormones that stimulate a decrease in blood glucose levels

Answer 17

Incretin

Question 18

Definition

a type of incretin-based medicine for type 2 diabetes. This type of medicine is based on the action of hormones called incretins, which help control how the pancreas works

Answer 18

GLP-1 receptor agonists

Question 19

Definition

surgery that affects your stomach and how you digest food. It’s designed to make your stomach much smaller, which causes you to feel full after eating only a small amount of food

Answer 19

Bariatric surgery

Question 20

Definition

marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is not associated with weight gain.

Answer 20

Metformin

Question 21

What are the complications of diabetes?

Answer 21

Macrovascular disease (heart attack, stroke, angina etc)

Microvascular disease (diabetic retinopathy, end-stage renal disease, neuropathy etc.)

Question 22

What causes the complications seen in diabetes?

Answer 22

Increased glucose levels cause an increase in glycosylation

Question 23

What is the most common cause of blindness in industrialised countries?

Answer 23

Diabetic retinopathy

Question 24

What percentage of diabetics have neuropathy?

Answer 24

50%

Question 25

What is the first-line treatment for diabetes?

Answer 25

Changing lifestyle habits (diet and exercise)

Question 26

What therapies are used for diabetes?

Answer 26

* Lifestyle (diet & exercise) * Metformin (e.g. Glucophage, Glumetza) * Sulfonyureas (e.g. Diabeta, Glucotrol) * GLP-1 receptor agonists (e.g. Exenedin/ Liraglutide) * DPP-4 inhibitors (e.g. Januvia, Onglyza) * Thiazolidinediones (TZDs; e.g. Avandia, Actos) * SGLT2 inhibitors new (e.g. Ivokana, Farxiga) * Insulin * Bariatric surgery

Question 27

What is the first-line pharamcological treatment for diabetes?

Answer 27

Metformin

Question 28

How does Metformin treat diabetes?

Answer 28

Prevents the progression of impaired glucose tolerance to T2DM by mimicing insulin Increases levels of AMPK which allows GLUT4 translocation

Question 29

How does Metformin act to improve glucose metabolism in the liver and skeletal muscle?

Answer 29

Question 30

Why are Sulfonylureas no longer the first-line treatment for diabetes?

Answer 30

Complications include: * May induce hypoglycemia as a result of excess insulin production and release (high dose, fasting). * Weight gain. * Can’t be used in pregnancy (may cause birth defects). * Can’t be used in renal / liver failure due to high risks of hypoglcemia.

Question 31

Why are Sulfonylureas not effective in T1D?

Answer 31

It acts to increase levels of insulin but insulin cannot be produced in T1D

Question 32

What is the mechanism of sulfonylurea action?

Answer 32

Sulfonylureas block ATP-sensitive potassium channels causes K+ to acculmulate in the cell. This causes cell depolarisation through calcium influx Increased calcium levels cause insulin to be released from pancreatic beta cells

Question 33

Where was GLP-1 receptor agonists originally found?

Answer 33

Saliva of the Gila monster

Question 34

What are GLP-1 receptor agonists?

Answer 34

Incretin mimetics The cause an increase in the amount of insulin released from the beta cells, even before glucose is is elevated Works within 10 minutes of administration

Question 35

What does the GLP-1 receptor do?

Answer 35

Inhibits food intake via GLP1-R GLP-1 act directly at POMC neurons Indirectly inhibits NPY/AGRP neurons via GABA

Question 36

What are the new generation drug development strategies for diabetes?

Answer 36

Monotherapies Combination Therapy Personalised Medicine Targeted Therapy

Question 37

Which type of new gen drug does not act in the brain?

Answer 37

Orlistat (lipase inhibitor)

Question 38

Where do the new generation drugs (Orlistat, Contrave, Liraglutide, Lorcaserin and Qsymia) act to treat diabetes?

Answer 38

* Lipase inhibitor * Orlistat * Predominant action via the melanocortin pathway * Contrave * Liraglutide * Lorcaserin * Wise-spectrum pharmacology acts at the brain * Qsymia

Question 39

What is the mode of action of Orlistat and what are the side-effects?

Answer 39

Inhibits lipase molecules preventing the breakdown and absorption of fats Side effects include include cramping, gas, diarrhea, anal leakage and oily underwear stains

Question 40

What is Lorcaserin and how does it treat diabetes?

Answer 40

Lorcaserin is a monotherapy that acts as a serotonin agonist selectively activates POMC neurons by targeting the 5-HT 2CR receptor specificlly

Question 41

What two drugs does contrave include?

Answer 41

Bupropion Naltrexone

Question 42

How do the two contrave drugs (Naltrexone and Bupropion) cause synergistic effects?

Answer 42

Bupropion stimulates POMC neurons to release α-MSH Naltrexone prevents the β-endorphin mediated POMC autoregulation

Question 43

How are POMC cells autoregulated?

Answer 43

POMC cells produce both α-MSH and β-endorphins. The endorphins act on self receptors to repress activity

Question 44

What is the only effect mechanims of long-term weight loss?

Answer 44

Bariatric surgery

Question 45

Why is a Roux-en-Y gastric bypass (RYGB) rarely used in Australia?

Answer 45

High rates of malnutrition

Question 46

At what point does the gastric band improve insulin sensitivity?

Answer 46

Following the weight loss caused by the surgery

Question 47

What effects does the gastric sleeve have on ghrelin and gut peptides?

Answer 47

↓ ghrelin ↑ GLP-1

Question 48

At what points does the gastric sleeve have an effect on insulin sensitivity?

Answer 48

Immediately irrespective of weight loss Rapid nutrient passage into the small intesitine causes increased post-prandial insulin secretion cause glucose uptake

Question 49

List the bariatric surgeries in order of decreasing effectiveness

Answer 49

1. RYGB 2. Sleeve (LSG) 3. Band (LAGB)