Diabetes drugs

Question 1

What class of drug is metformin?

Answer 1

Biguanide

Question 2

Give examples of sulphonylureas

Answer 2

Gliclazide

Glibenclamide

Question 3

Name a GLP - 1 agonist

Answer 3

Exenatide

Question 4

Give an example of a DDP - 4 inhibitor

Answer 4

Sitagliptin

Question 5

Give an example of a thiazolidinedione (TZD)

Answer 5

Pioglitazone

Question 6

What’s the first line drug for T2DM?

Answer 6

Metformin

Question 7

Is metformin safe in pregnancy?

Answer 7

Yes!

Question 8

What effect does metformin have on weight?

Answer 8

Weight loss

Question 9

How does metformin work?

Answer 9

INCREASE INSULIN SIGNALLING:

Decreases hepatic gluconeogenesis by stimulating AMP-activated protein kinases

Increases glucose uptake by skeletal muscle (by increasing insulin signalling)

Increase fatty acid oxidation

Question 10

Side effects of metformin?

Answer 10

GI upset

Lactic acidosis

Liver damage and renal toxicity IF GFR IS ALREADY <30ml/min

Question 11

What’s the risk of using metformin in kidney disease?

Answer 11

lactic acidosis

Question 12

Can metformin cause hypoglycaemia?

Answer 12

No!

Question 13

How do sulphonylureas work?

Answer 13

They bind to the SUR1 part of K+ ATP channels in pancreatic beta cells and cause depolarisation.

This results in Ca2+ influx and insulin release

Question 14

Why can’t SUs be used in T1DM?

Answer 14

They require good beta cell function to work

Question 15

Can SUs cause hypoglycaemia? Why / why not?

Answer 15

Yes! They close K ATP channels regardless of blood glucose levels

Question 16

Briefly describe the physiology of insulin release

Answer 16

1. Glucose enters beta cells via GLUT2
2. It is metabolised by glycolysis / Krebs cycle to form ATP
3. An increase ATP:ADP ratio within the cell causes K+ ATP channels to close, resulting in depolarisation (due to increased intracellular K+)
4. This allows voltage activated Ca2+ channels to open, causing an influx of calcium into the cell
5. Calcium mediated exocytosis of insulin follows

Question 17

Side effects of sulphonylureas?

Answer 17

HYPOGLYCAEMIA

Weight gain

Headaches

GI upset

Question 18

Effect of SUs on weight?

Answer 18

Cause weight GAIN

Question 19

What’s the “reverse tick” effect and which drug class is it associated with?

Answer 19

SUs

They work effectively initially, but efficacy decreases over time

Question 20

What does GLP stand for (as in GLP1 agonists)? Give another example of an incretin

Answer 20

Glucagon like peptide

Other incretins include GIP

Question 21

Physiologically, what do incretins (like GLP) do?

Based on that, how do GLP-1 agonists work?

Answer 21

Incretins are released from cells in the small intestine after a meal and stimulate insulin.

This increases cell uptake of glucose and lowers blood sugar.

GLP1 agonists (e.g exenadite) mimic incretins to enhance insulin secretion

Question 22

Side effects of GLP-1 agonists?

Answer 22

Nausea

Decreased appetite

Very rarely pancreatitis (? and pancreatic cancer)

Question 23

Effect of GLP-1 agonists on weight?

Answer 23

Weight loss due to decreased appetite

Question 24

Can GLP-1 agonists cause hypoglycaemia?

Answer 24

No

Question 25

Physiologically, what does DPP4 do? Based on this, how do DPP4 inhibitors work?

Answer 25

DPP4 breaks down incretins (such as GLP and GIP). DPP4 inhibitors prolong the glucose-lowering actions of GLP-1 and GIP.

Question 26

Side effects of DPP4 inhibitors?

Answer 26

Nausea Pancreatitis (rare) Much less potent than GLP-1 agonists - They only work prolonging the action of incretins that are present (and levels are low in T2DM)

Question 27

Do DPP4 inhibitors (sitaglipin) cause weight loss?

Answer 27

No

Question 28

How are GLP-1 agonists administered?

Answer 28

SC injection

Question 29

How do TZDs work?

Answer 29

Enhance the action of insulin at target sites (by acting as exogenous agonists of nuclear receptors) Act on PPARgamma receptors (They're insulin sensitisers)

Question 30

Side effects of TZDs?

Answer 30

Weight gain Fluid retention Increased incidence of bone fractures (avoid if heart failure, obese or osteoporotic)

Question 31

Can TZDs cause hypoglycaemia?

Answer 31

Only if used with SUs

Question 32

How do SGLT2 inhibitors work?

Answer 32

Selectively block reabsoption of glucose by Na / glucose transporters in the proximal tubule, deliberately causing glucosuria and lowering blood sugar

Question 33

Side effects of SGLT2 inhibitors?

Answer 33

Thrush UTI

Question 34

Effect of SGLT2 inhibitors on weight? Risk of hypo?

Answer 34

Weight loss (pee out glucose) Little risk of hypo

Question 35

From the following list, which drugs cause weight loss? Metformin SUs (gliclazide) GLP-1 agonists (exenatide) DPP4 inhibitor (sitigliptin) PTZ (pioglitazone) SGLT2 inhibitor (dapagliflozin)

Answer 35

Metformin GLP-1 agonist SGLT2 inhibitors

Question 36

Which of the following cause weight gain? Metformin SUs (gliclazide) GLP-1 agonists (exenatide) DPP4 inhibitor (sitigliptin) PTZ (pioglitazone) SGLT2 inhibitor (dapagliflozin)

Answer 36

SUs PTZ

Question 37

Which of the following may cause hypoglycaemia? Metformin SUs (gliclazide) GLP-1 agonists (exenatide) DPP4 inhibitor (sitigliptin) PTZ (pioglitazone) SGLT2 inhibitor (dapagliflozin)

Answer 37

SUs