diabetes drugs

Question 1

what are 5 groups of T2DM drugs?

Answer 1

1. metformin (1st line)
2. sulphonylureas
3. incretin drugs
4. SGLT2 inhibitors
5. thiazolidinediones

Question 2

what is mode of action of metformin?

Answer 2

it inhibits gluconeogenesis so lowers hepatic glucose production

*also increases GLP-1 secretion & increases gut glucose utilisation & metabolism

Question 3

what are side effects of metformin? how can you reduce side effects?

Answer 3

GI intolerance so diarrhoea, bloating, abdo pain and dyspepsia

• normal prescription is 500mg once daily. to help side effects you can initiate slowly with 500mg once a week or modified release formulation

Question 4

what is mode of action for sulphonylureas?

Answer 4

they act on pancreatic beta cells to increase insulin secretion (insulin secretagogues) = independent of glucose

Question 5

what is drug example of sulphonylurea?

Answer 5

gliclazide

Question 6

what is main clinical risk of sulphonylureas? side effects?

Answer 6

hypoglycaemia - they’re glucose independent (meaning can make insulin even if glucose low or normal) so they can just keep lowering & lowering glucose = hypoglycemia risk (means risk for driving, DVLA)

• additional side effect of weight gain as insulin increases appetite
• also maybe increase CV risk but unclear

Question 7

what is incretin?

Answer 7

incretin is intestinal secretion of insulin

• Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are hormones in intestine that work together to increase insulin secretion after eating

*GLP-1 has loads of effects including increasing insulin sensitivity

Question 8

what have the roles of triggering and amplifying of beta cell production out of sulphonylurea & incretins?

Answer 8

• basically sulphonylureas & glucose trigger the insulin pathway and incretins can amplify

*triggering & amplifying pathways of beta cell via GLP-1 (causes insulin sensitivity)

Question 9

what are the 2 types of incretin drugs? and examples of each?

Answer 9

1. DPP 4 inhibitors e.g. sitagliptin
2. GLP-1 receptor agonists e.g. liraglutide (injection) or semaglutide (oral)

Question 10

what is action of DPP 4 inhibitor? (incretin drug)

Answer 10

weak but smart sulphonylurea like drug = weakly increases insulin secretion by inhibiting breakdown of GLP-1 and GIP

Question 11

what are side effects of DPP 4 inhibitors? (barely any)

Answer 11

minimal side effects, possible pancreatitis risk

*main good thing = is since incretin glucose dependent they do NOT cause hypoglycaemia

Question 12

what is GLP-1 receptor agonist mode of action? (incretin drug)

Answer 12

they mimic GLP-1 by binding to GLP-1 receptors and stimulating them (generally more sustained effects on blood glucose)

= promotes insulin secretion in glucose dependent mechanism, also weight loss & CV & renal benefits

Question 13

what are side effects of GLP-1 receptor agonists?

Answer 13

nausea & vomiting, gallstones, maybe pancreatitis

Question 14

what is mechanism of action of SGLT2 inhibitors?

Answer 14

inhibit sodium glucose transporter which causes you to pee out glucose & lose calories so weightloss

Question 15

what is common examples of SGLT2 inhibitors?

Answer 15

dapagliflozin, canagliflozin, empagliflozin

Question 16

what are some additional complex consequences (good things) for SGLT2 inhibitors?

Answer 16

• has mild diuretic action so good for heart failure (good getting rid of fluid)
• renal protection (through complex mechanism)
• improved myocardial energetics (less glucose means increase in lipolysis to get energy which makes ketone bodies which are good energy for cardiac myocytes)

Question 17

what are side effects of SGLT2 inhibitors?

Answer 17

• UTI’s & thrush (secondary to glycosuria)
• fournier gangrene (rare infection to genital & perineum)
• hypovolaemia & hypotension
• diabetic ketoacidosis (if too much ketone bodies made then bad)

Question 18

what is main action of thiazolidinediones?

Answer 18

they target PPAR-gamma receptors in fat cells to help store fat more effectively (increase fat mass so less floating in blood stream) which means better cytokines and less bad ones around. this means increase insulin sensitivity

(only true insulin sensitizer drugs in TD2M)

Question 19

what is example of thiazolidinediones?

Answer 19

pioglitazone

Question 20

what are side effects of thiazolidinediones?

Answer 20

• weight gain
• fluid retention = peripheral oedema & doubling risk of hospitalisation for cardiac failure
• fracture risk due to fat accumulation in bone marrow & reduction in bone density

Question 21

what are 2 drugs improving cardio & renal outcomes?

Answer 21

SGLT2 inhibitors and GLP agonist (incretin drug)

Question 22

which drug should be avoided if liver & kidney problems?

Answer 22

metformin! = big side effect of lactic acidosis (rare but very important)

• measure kidney function through filtration rate, if filtering rate low (below 25) then avoid metformin

Question 23

what drug should be avoided in heart failure?

Answer 23

pioglitazone (TZD) as causes fluid overload

Question 24

what drugs should be stopped if sick?

Answer 24

SGLT2 or metformin