Diabetes Medication - Metformin, Sulphonylureas, TZDs, Incretins, SGLT2 Inhibitors

Question 1

What is the molecular mechanism of metformin?

Answer 1

Inhibits complex 1 of the mitochondrial respiratory chain resulting in a fall in intracellular ATP

Question 2

What are the physiological mechanisms of metformin?

Answer 2

Lowers hepatic glucose production

Increases gut glucose utilisation and metabolism

Question 3

What are the sites of action of metformin?

Answer 3

Intestines, Liver, Kidneys.
This is because the metformin molecules are largely hydrophilic therefore require active transport to enter the cells via the Organic Cation Transporter. These OCT are present in the above locations.

Question 4

What are the side effects of metformin?

Answer 4

Gastrointestinal Intolerance - to reduce the effects start the medication slowly
Metformin Associated Lactic Acidosis- this is because metformin increases lactate production; associated with kidney problems

Question 5

What is the molecular mechanism of sulphyonylureas?

Answer 5

Inhibit ATP-dependent K+ channels in pancreatic beta cells. This increases membrane potential and Ca2+ influx leading to subsequent insulin release.

Question 6

What is the physiological mechanism of sulphonylureas?

Answer 6

Stimulate pancreatic insulin secretion

Question 7

Name some sulphonylureas…

Answer 7

GLICLAZIDE

Question 8

What are the side effects of sulphonylureas?

Answer 8

Hypoglycaemia
Weight gain - insulin increases appetite
Cardiovascular Risk

Question 9

What is the molecular mechanism of Thiazolidinediones?

Answer 9

They are PPAR gamma ligands which result in the switching on of hundreds of genes

Question 10

What is the physiological mechanism of Thiazolidinediones?

Answer 10

The main effect is on adipocytes.
They increase differentiation from pre-adipocytes to adipocytes which increases subcutaneous fat mass. This fat is drawn put of the liver and muscle which reduces lipotoxicity adn increses insulin secretion

Question 11

Name a TZD…

Answer 11

Pioglitazone

Question 12

What are the side effects of TZDs?

Answer 12

Weight Gain, Fluid Retention, Fracture Risk

Question 13

What drug type is the only true insulin sensitiser?

Answer 13

TZDs

Question 14

What are the two types of incretin drugs?

Answer 14

DPP4 Inhibitors

GLP-1 Receptor Antagonist

Question 15

What is the mechanism of DDP4i?

Answer 15

Inhibit the breakdown of the incretins, GLP-1 and GIP. This promotes insulin secretion.

Question 16

Name examples of DDP4i?

Answer 16

Sitaglipin, Linaglipin, Saxaglipin

Question 17

What are the side effects of DDP4i?

Answer 17

Generally minimal
Hypoglycaemia
Pancreatitis

Question 18

What is the mechanism of GLP-1 RA?

Answer 18

Promote insulin secretion in a glucose dependent mechanism. They also act on the hypothalamus to reduce appetite and on the intestine to reduce gastric emptying

Question 19

What are examples of GLP-1 RA?

Answer 19

Liraglutide, Semaglutide

Question 20

What are side effects of GLP-1 RA?

Answer 20

Nausea
Vomiting
Gallstones
Pancreatitis

Question 21

What is the molecular mechanism of SGLT2 Inhibitors?

Answer 21

They inhibit the SGLT2 Transporter in the kidney. This prevents glucose resorption in the kidney and hence leads to glucose excretion via the urine.

Question 22

What are the other impacts of SGLT2 Inhibitors?

Answer 22

Renal Protection
CVD Benefit
Increase Ketone Body Production

Question 23

Name some SGLT2 Inhibitors…

Answer 23

Empagliflozin
Dapagliflozin
Canagliflozin

Question 24

What are some side effects of SGLT 2 Inhibitors?

Answer 24

Thrush
Fournier Gangrene
Hypovoleamia
Hypotension
Diabetic Ketoacidosis