Lecture 18 - Medicines for Type 2 Diabetes

Question 1

What type of medicine is metformin?

Answer 1

a biguanide

Question 2

What is metformin?

Answer 2

first line oral glucose lowering agent for type 2 diabetes

Question 3

How many people is metformin prescribed to?

Answer 3

83.6% of patients in the UK with type 2 diabetes (2013)

Question 4

What are the advantages of metformin?

Answer 4

it doesn’t cause weight gain or hypoglycaemia

can be used in overweight patients

Question 5

When was metformin first used?

Answer 5

1953

Question 6

What is the most important effect of metformin?

Answer 6

to reduce hepatic glucose production

Question 7

Mechanism of action of metformin?

Answer 7

still unknown

can affect multiple cellular processes and the most widely accepted is linked to inhibition of mitochondrial respiratory chain-complex 1

Question 8

How does metformin enter hepatocytes?

Answer 8

through the organic cation transporter 1

Question 9

What does inhibiton of the complex 1 of the respiratory chain cause?

Answer 9

inhibition of ATP synthesis

increase in AMP

activation of AMPK

phosphorylation and inhibition of CRTC2

inhibition of gluconeogenic gene expression

Question 10

What is CRTC2?

Answer 10

a transcription factor that normally plays a role in transcription of genes involved in gluconeogenesis so when blocked it leads to decreased synthesis of genes and reduction in glucose production

Question 11

Side effects of metformin?

Answer 11

GI effects such as diarrhoea, nausea, vomiting, abdominal bloating, reduced appetite

vit B12 deficiency

Question 12

What % of patients on metformin have a reduced appetite?

Answer 12

20%

Question 13

What % of patients discontinue metformin use from GI side effects?

Answer 13

5%

Question 14

How does metformin cause B12 deficiency?

Answer 14

it reduces intestinal absorption of vit B12 in up to 30% of patients and lower serum levels in a dose-dependent manner in 5-10% of patients

Question 15

What symptoms does B12 deficiency cause?

Answer 15

tiredness and tingling in hands and feet

Question 16

What is a rare side effect of metformin?

Answer 16

lactic acidosis

Question 17

Brands of metformin?

Answer 17

bolamyn
diagment
glucient 
glucophage
metabet

Question 18

What do sulfonylureas do?

Answer 18

stimulate insulin secretion from pancreatic beta cells

Question 19

How to sulfonylureas work?

Answer 19

they bind to ATP-gated K+ channels, causing channel closure and membrane depolarisation, which causes calcium to enter the cell and stimulate insulin secretion

Question 20

Daonil?

Answer 20

glibenclamide

Question 21

Diamicron, Diamicron MR?

Answer 21

gliclazide

Question 22

Glibenese, Minodiab?

Answer 22

Glipizide

Question 23

Amaryl?

Answer 23

glimepiride

Question 24

Tolbutamide?

Answer 24

tolbutamide

Question 25

Names of sulfonylureas?

Answer 25

glibenclamide, gliclazide, glipizide, glimepiride, tolbutamide

Question 26

Side effects of sulfonylureas?

Answer 26

Hypoglycaemia, can also cause weight gain

Question 27

What are meglitinides?

Answer 27

prandial glucose regulators

Question 28

Mechanism of action of meglitinides?

Answer 28

similar mechanism to sulfonylureas but rapid onset and short duration

Question 29

When are meglitinides taken?

Answer 29

before meals

Question 30

Examples of meglitinides?

Answer 30

repaglinide, nateglinide

Question 31

Prandin?

Answer 31

repaglinide

Question 32

Starlix?

Answer 32

Nateglinide

Question 33

What are thiazolidinediones?

Answer 33

Glitazones

Question 34

What is the only tablet in the thiazolidinediones?

Answer 34

pioglitazone

Question 35

How do glitazones work?

Answer 35

increase insulin sensitivity by stimulating the expression of insulin sensitising genes they are insulin sensitisers

Question 36

What do thiazolidinediones bind to?

Answer 36

the nuclear receptor PPAR gamma

Question 37

What does PPAR gamma do?

Answer 37

works with retinoid X receptor to drive the expression of insulin sensitising genes

Question 38

What are examples of insulin sensitising genes?

Answer 38

GLUT4, PI3 kinase, IRS proteins

Question 39

Medicines in the thiazolidinedione group?

Answer 39

pioglitazone, and pioglitazone in combination with metformin

Question 40

Actos?

Answer 40

pioglitazone

Question 41

Competact?

Answer 41

pioglitazone & metformin

Question 42

Side effects of thiazolidinediodes?

Answer 42

water retention (oedema) and weight gain

Question 43

What are GLP-1 analogues?

Answer 43

incretin mimetics glucagon like peptide 1 analogues that increase insulin release

Question 44

What is GLP1

Answer 44

glucagon like peptide 1

Question 45

What happens when GLP1 is released?

Answer 45

following food intake released with GIP, they activate or stimulate insulin release from pancreatic beta cells

Question 46

GLP and GIP are degraded by?

Answer 46

they have short have lives and are degraded by protease DPP4

Question 47

Examples of GLP-1 analogues

Answer 47

exenatide, liraglutide, lixisenatide, dulaglutide, semaglutaide

Question 48

Byetta?

Answer 48

exenatide (twice daily injection)

Question 49

Bydureon?

Answer 49

exenatide (once weekly injection)

Question 50

Victoza?

Answer 50

liraglutide (once daily injection)

Question 51

Lixumia?

Answer 51

lixisenatide (once daily injection)

Question 52

Trulicity?

Answer 52

dulaglutide (once weekly injection)

Question 53

Ozempic?

Answer 53

semaglutide (once weekly injection)

Question 54

What are DPP4 inhibitors?

Answer 54

gliptins they bind to DPP4 and inhibit its activity, which allows endogenously produced GLP-1 and GIP to accumulate to higher levels and stimulate more secretion of insulin

Question 55

DPP4 medicines?

Answer 55

sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin

Question 56

Januvia and janumet?

Answer 56

sitagliptin sitaglipin & metformin

Question 57

galvus and eucreas?

Answer 57

Vildagliptin vildagliptin & metformin

Question 58

Onglyza & Kombolyze?

Answer 58

saxagliptin saxagliptin & metformin

Question 59

Vipidia & vipdomet?

Answer 59

alogliptin alogliptin & metformin

Question 60

Trajenta & Jentadueto?

Answer 60

linagliptin linagliptin & metformin

Question 61

What do alpha glucosidase inhibitor (Acarbose) do?

Answer 61

slow down the absorption of starchy foods by intestine - slows the rise in blood glucose after a meal

Question 62

What do SGLT2 inhibits do?

Answer 62

act by inhibiting glucose transporter SGLT2, which functions in the kidney to mediate glucose reabsorption, excess glucose is lost in urine

Question 63

Examples of SGLT2 inhibitors?

Answer 63

dapagliflozin, empagliflozin, canagliflozin

Question 64

Forxiga?

Answer 64

dapagliflozin

Question 65

Invokana?

Answer 65

canagliflozin

Question 66

Jardiance?

Answer 66

empagliflozin

Question 67

What else is important to control symptoms of type 2 diabetes?

Answer 67

eating a healthy diet and regular exercise

Question 68

What else may be prescribed if glucose control is not adequate in type 2 diabetes?

Answer 68

Insulin

Question 69

What has type 2 been discovered as?

Answer 69

A reversible disease

Question 70

What happens if monotherapy does not work for someone with type 2 diabetes?

Answer 70

an additional oral antidiabetic might be added, can also move to triple therapy if this is not enough

Question 71

Surgery for diabetes?

Answer 71

~65% of patients with type 2 diabetes were no longer on any diabetic medication 2 years after bariatric surgery

Question 72

What have NICE recommended with surgery?

Answer 72

all patients in the UK with BMI>35 with recent onset type 2 diabetes should be assessed for surgery

Question 73

What is the initial cost of surgery?

Answer 73

~£6,000

Question 74

What else has been shown to put type 2 diabetes into remission?

Answer 74

a very low calorie diet of about 600-700 calories per day can put diabetes into remission after 4-6 weeks

Question 75

What is the success of the low calorie diet correlated with?

Answer 75

weight loss - fat loss from pancreas and the liver