T2DM Drugs

Question 1

Describe insulin release.

Answer 1

Glucose enters ß-cells through GLUT2

Glucose phosphorlyates to glucose-6-phosphate in cytoplasm by glucokinase increasing ATP:ADP ratio

ATP closes KATP channel by acting on Kir6 suninits
(ADP opens channel by acting on SUR1 subunit)

Closure of KATP channel depolarises the cell membrane which opens voltage-gates-Ca channels increasing intracellular Ca

Intracellular Ca releses insulin from secretory vesicles

Question 2

Is more insulin produced in response to oral glucose of IV glucose.

Why?

Answer 2

Oral glucose produces more insulin

Oral glucose stimulates release of GLP-1 from stomach which amplifies insulin and delays gastric emptying

GLP-1 is quickly inactivated by DPP-4 enzyme

Question 3

What is the mechanism of action of metformin?

Answer 3

Insulin sensitiser

Question 4

What is the first line medication in T2DM?

Answer 4

Metformin

Question 5

What is metformin’s effect on weight?

Answer 5

Can reduce weight

Question 6

Which T2DM drugs carry a risk of hypoglycamia?

Answer 6

Sulphonylureas

Question 7

What are some side effects of metformin?

Answer 7

GI upset

Lactic acidosis

Question 8

What doses of metformin are used?

Answer 8

Start at 500mg

Titrate up to maximal 1000mg BD as needed

If eGFR

Question 9

What are some contraindications to metformin?

Answer 9

eGFR<30 (CKD G4)

Creatinine>150

Question 10

Name a sulphonylurea.

Answer 10

Gliclazide

Question 11

How do sulphonylureas work?

Answer 11

Block ADP binding on KATP channel (SUR1 subunit) which prevents opening of the channel, depolarising the membrane and releasing insulin

(this works independently of glucose and so hypoglycaemia is a risk)

Question 12

What are some side effects of sulphonylureas?

Answer 12

Weight gain

Headache

Question 13

What are the indications of sulphonylureas?

Answer 13

Second line add on to metformin

First line if metformin intolerant or contraindicated (poor renal function)

Question 14

What is pioglitazone?

Answer 14

Thiazolidinedione (TZD) / PPAR-y agonist

Question 15

How do PPAR-y agonists work?

Answer 15

Bind to transcription factor PPAR-y which alters gene transcription and up regulates insulin action

Question 16

What are some side effects of PPAR-y agonist?

Answer 16

Fluid retention

Reduced bone density

Question 17

What are the contraindications to PPAR-y use?

Answer 17

Heart failure

Renal failure

Over 65s (reduced bone density)

Question 18

What do SGLT-2 inhibitors do?

Answer 18

Inhibit glucose reabsorption resulting in glucose excretion

Question 19

What are some side effects on SGLT-2 inhibitors?

Answer 19

Thrush

UTI

Question 20

What are contraindications to SGLT-2 inhibitor use?

Answer 20

Renal failure

Question 21

Name an SGLT-2 inhibitor.

Answer 21

Dapagliflozin

Question 22

What are gliptins? How are they administered?

Answer 22

DDP-4 inhibitor

Oral

Question 23

Name a DDP-4 inhibitor.

Answer 23

Vildagliptin

Question 24

How do DDP-4 inhibitors work?

Answer 24

Inhibit DDP-4 preventing GLP inactivation which amplifies insulin release

Question 25

Which of DDP-4 inhibitors and GLP agonists are 1. injected and PO? 2. more potent and why?

Answer 25

1. DDP-4 inhibitors oral and GLP agonists injected | 2. DDP-4 inhibitors are less potent as they require endogenous GLP production which is low in T2DM

Question 26

What drugs are associated with an increased risk of pancreatitis and pancreatic cancer?

Answer 26

GLP agonists DDP-4 inhibitors

Question 27

What class of drug is exenatide?

Answer 27

GLP-1 receptor agonist

Question 28

Name a GLP-1 receptor agonist.

Answer 28

Exenatide

Question 29

How do GLP-1 receptor agonists work?

Answer 29

Amplify insulin release by acting on GLP-1 receptor

Question 30

What are GLP-1 receptor agonists effect on weight?

Answer 30

Weight loss via reduced appetite and delayed gastric emptying

Question 31

Name the injected therapies available to T2DM patients.

Answer 31

GLP-1 receptor agonists Insulin

Question 32

Name the 7 drug classes used in T2DM, give an example and its administration route.

Answer 32

Metformin, oral Sulphonylurea, gliclazide, oral PPAR-y agonist, pioglitazine, oral SGLT-2 inhibitor, dapraflozin, oral DDP-4 inhibitor, vildagliptin, oral GLP-1 receptor agonist, exenaide, injected Insulin, injected