Endo - Diabetes Drugs

Question 1

Metformin - how does it work, what effect does it have on weight, and side effects?

Answer 1

Works - Increases insulin sensitivity and decreases liver production of glucose

Weight - weight neutral

Side effects - GI disturbances, lactic acidosis, does NOT CAUSE hypoglycaemia

Question 2

Thiazolidinedione (pioglitazone) - how does it work, what effect does it have on weight, and side effects?

Answer 2

How does it work - increases insulin sensitivity and decreases liver production of glucose

Weight - weight gain

Notable side effects - weight gain, fluid retention, HF, increase risk of bladder cancer, fractures, anaemia

Does NOT CAUSE hypoglycaemia

Question 3

Sulfonylurea - how does it work, what effect does it have on weight, and side effects?

Answer 3

Gliclazide

Works - stimulates insulin release from pancreas

Side effects - weight gain, hypoglycaemia, hyponatraemia secondary to SIADH, increased risk of MI and CV disease if used as monotherapy

Question 4

Incretins (relevant for DPP-4 inhibitors and GLP-1 mimetics) - how do they work?

Answer 4

Incretins - hormones produced by GI tract, secreted in response to large meals and act to reduce blood sugar, they can:

• Increase insulin secretions
• Inhibit glucagon production
• Slow absorption by GI tract

Main incretin is glucagon-like peptide-1 (GLP-1)

Incretins inhibited by enzyme called dipeptidyl peptidase-4 (DPP-4)

Question 5

DPP-4 inhibitor - how does it work, what effect does it have on weight, and side effects?

Answer 5

Example - Sitagliptin

Works - Inhibits DPP-4 enzyme, therfore increasing GLP-1 activity

Side effects - GI disturbances, symptoms of upper respiratory tract infection, pancreatitis

Question 6

GLP-1 mimetics - how does it work, what effect does it have on weight, and side effects?

Answer 6

Example - exenatide, given as subcut injection BD, or once weekly in modifiable-release form

Side effects - GI disturbances, WEIGHT LOSS, dizziness, low risk of hypoglycaemia

Question 7

SGLT-2 Inhibitors - how does it work, what effect does it have on weight, and side effects?

Answer 7

Example - end with ‘glifozin’, empaglifozin, canaglifozin, dapaglifozin

Works - SGLT-2 protein responsible for reabsorbing glucose from urine into blood in proximal tubules of kidneys, so SGLT-2 inhibitors block action of this protein, cause glucose to be excreted in urine

Side effects - Glucoseuria, increased UTIs, WEIGHT LOSS, DKA with only moderately raised glucose, lower limb amputation appears to be more comon in patients on canaglifozin