10. Diabetes Drugs

Question 1

Describe the role of insulin

Answer 1

• anabolic hormone
• stimulates uptake of glucose into liver, muscle and adipose
• inhibits gluconeogenesis and glycogenolysis
• promote the uptake of fat

Question 2

Within what range do we want out blood glucose levels?

Answer 2

4-7 mmol/L

-insulin levels rise following a meal to keep glucose levels within range

Question 3

Which region of insulin is altered in recombinant DNA technology?

Answer 3

B26-30 region

Question 4

Name the 6 main insulin categories

SILVUR

Answer 4

Short acting
Intermediate acting
Long acting 
Very long acting
Ultrafast acting - aspart 
Rapid acting

Question 5

How does ultrafast acting insulin work?

Answer 5

• as glucose rises the insulin aspart mimics the normal and prevents glucose from rising higher

Question 6

How does rapid acting insulin work?

Answer 6

• inject just before eating meal
• onset within 5 -15 mins (rapid)
• duration 4-6 hours
• peak concentration reached in 60 mins

Question 7

How does short acting insulin work?

Answer 7

• inject 15-30 mins before meal , several times daily
• starts to work within 30-60 mins
• duration of 8-10 hours

Question 8

Why does blood glucose rise?

Answer 8

• inability to produce insulin due to beta cell failure (Type 1)

And/or

• insulin production is adequate but insulin resistance prevents insulin from working adequately (type 2)

Question 9

What is the target for glycated Hb (HbA1c)?

Answer 9

6.5-7.5%

Glycated Hb lives for 3 months, circulates and if your glucose is too high it will pick up more glucose

Question 10

How do biguanides e.g. metformin work?

Answer 10

• decreases insulin resistance
• increases glucose uptake by tissues and reduces hepatic gluconeogenesis
• limits weight again and reduces CVS events
• can be combined with all other diabetes medications

Question 11

What are the side effects of metformin?

Answer 11

• GI side effects e.g. diarrhoea, wind, upset stomach
• lactic acidosis rare
• stop if CKD <30ml/min

Question 12

How do sulphonylureas e.g. gliclazide work? Any side effects?

Answer 12

• they stimulate beta cells to release insulin
• this can lead to increase appetite and weight gain which is a side effect
• can also get hypoglycaemia
• dont want to give it to elderly patients

Question 13

How do DDP4 inhibitors e.g. Sitagliptin work and are there any side effects?

Answer 13

• inhibit DDP4
• increase post prandial GLP-1 concentrations
• weight neutral and modest HbA1c reduction
• can cause GI symptoms and possible pancreatitis

Question 14

How do thiazolidinediones e.g. pioglitazone work?

Answer 14

• decrease insulin resistance
• reduce hepatic gluconeogenesis
• but they are hardly used anymore due to adverse effects including weight gain, fluid retention, heart failure, effects on bone metabolism and bladder cancer

Question 15

How do a-glucosidase inhibitors work e.g. acarbose?

Answer 15

• inhibits the breakdown of carbohydrates to glucose by blocking the action of a-glucosidase
• side effects include flatulence, loose stools and diarrhoea due to complex carbs
• rarely if ever used nowadays

Question 16

How do SGLTS work e.g. glifozins and side effects?

Answer 16

• add on therapy
• blocks renal tubule from absorbing glucose so you pee it out
• widely used with other meds or insulin
• side effects include risk of UTIs especially due to candida and potentially an osmotic diuresis , polyuria
• patients can lose energy and weight

Question 17

How do GLP1 analogues e.g. Exenatide work?

Answer 17

• GLP1 normally acts on beta cells to stimulate the release of insulin
• decreases production of glucagon from alpha cells
• promotes satiety and increases weight loss
• GI symptoms: loose stool, diarrhoea, nausea

Avoid if EGFR <30ml/min

Question 18

Name the classes of non insulin drugs for diabetes

Mnemonic: STAB DIGS (includes insulin)

Answer 18

S: sulphonylureas
T: thiazolidinediones 
A: a-glucosidase inhibitors
B:biguanides
D: DDP4 inhibitors
I: insulin (SILVUR)
G: GLP1 analogues
S: SGLT2’s