Diabetic Drugs

Question 1

Name 8 drugs used for diabetes treatment.

Answer 1

Diet and exercise
1 hr 3x week more effective than metformin
Metformin (Biguanide)
Sulphonylurea (gliclazide)
Insulin sensitizers: thiazelidinedione e.g. pioglitazone (rosaglitazone revoked due to HF fears)
Incretins/GLP-1 analogues (exenatide, liraglutide)
Gliptins/DPP4 inhibitors (sitagliptin, linagliptin)
SGLT2 inhibitors (canagliflozin, empagliflozin)
Insulin
several analogues available
caveat: increases hunger
as T2DM progresses, many patients given insulin

Question 2

What are the 3 C’s of diabetic patients

Answer 2

Control - bgl monitoring, HbA1c in target range? if not add another drug/ titrate up the dose

Complications - retinopathy, nephropathy (urine albumin creatinine ratio), neuropathy (look at feet), microvascular signs (chest pain, PVD)

Cardiovascular risk factors - BP, cholesterol levels

Question 3

Metformin
What is the
a) class of this drug
b) MOA
c) typical timeline of metformin treatment
c) side effects/contraindications

Answer 3

Biguanide
b) Given if diet alone not worked
↑ peripheral disposal of glucose
↑ insulin sensitivity in liver
Reduced HGO
c) increasingly titrate up dose of met forming. Check every 3 months and check HbA1c. If HbA1c(glucose indicator) not on target, then add another drug
d) gastrointestinal side effects (diarrhoea, vomiting)
ContraIx: liver/cardiac/renal failure/hypoxia/sepsis/hypotensive, as may get lactic acidosis

NB. now EVERYONE goes on metformin regardless of BMI

Question 4

Gliclazide 
What is the 
a) class of this drug
b) MOA
c) side effects/contraindications

Answer 4

a) sulphonylurea
b) blocks ATP sensitive K channels. hence cell depolarisation and Ca influx causes insulin release by pancreatic beta cells.
note need some residual beta cell function for sulphonylureas to work
c) SE: weight gain (use in lean patients)
hypoglycaemia

Question 5

Pioglitazone
What is the 
a) class of this drug
b) MOA
c) side effects/contraindications

Answer 5

a) Thiozolidinedione
b) decreases insulin resistance
(peroxisome proliferator activated receptor agonist)
c) SE: hepatitis, HF, peripheral weight gain
fluid retention, increased risk of MI and osteoporosis
*thought to have link to bladder cancer but unproven - thiozolidinediones are rarely used

Question 6

Exanatide, Liraglutide    
What is the 
a) class of this drug
b) MOA
c) side effects/contraindications

Answer 6

a) GLP-1 analogue
(also called incretins as stimulate insulin release indirectly)

b) enhance glucose-stimulated insulin release
GLP-1 = Gut hormone secreted in response to nutrients in gut from L cell. Functions are to:
Stimulate insulin synthesis and release
Decrease [glucagon/glucose]
Increase beta cell differentiation and glucose sensitivity

c) short half -life (degraded by dipeptidyl peptidase-4/DPP4)
   decreased appetite (good!!) and increased weight loss

Question 7

Gliptin, Sitagliptin, Vildagliptin    
What is the 
a) class of this drug
b) MOA
c) side effects/contraindications

Answer 7

a) DPP4 inhibitor
b) inhibiting DPP4 enzymes stops GLP-1 hormone degradation, hence more glucose induced insulin release
c) weight neutral

Question 8

Empagliflozin,  Canagliflozin
What is the 
a) class of this drug
b) MOA
c) side effects/contraindications

Answer 8

a) SGLT2 inhibitors

b) inhibit renal Na/glucose co-transporters, hence inhibit glucose reabsorption in kidney

Question 9

Insulin use in Type 1 diabetes

Answer 9

There is constant basal amount of insulin released by pancreas, with bursts of larger amounts of insulin (bolus insulin) released after meals.
If someone’s pancreas not making sufficient insulin, you want to mimic that physiological release of insulin.
T2DM patients are given insulin when disease has progressed to stage where no longer producing sufficient insulin.

Question 10

What is an insulatard?

Answer 10

basal insulin
insulin analogue
also called isophane insulin or NPH (neutral protamine Hagedorn)
NPH added to insulin to increase it’s duration of action
doa 12-18 hrs

protamine from fish semen

Question 11

What type of insulin is Glargine? Describe the composition.

Answer 11

Basal insulin
Insulin analogue
Due to altered aa composition, when injected subcutaneously it forms aggregates which are SLOWLY absorbed into the blood
doa 24 hrs

Question 12

What type of insulin is Determir? Describe the composition.

Answer 12

basal insulin
insulin analogue
has fatty acid chain that allows insulin to bind to albumin, allowing slow release and absorption of insulin

Question 13

Describe the absorption/release of bolus insulin.
Give three examples of bolus insulin given on wards.

•Bolus
–Rapid onset, short duration of action
–Soluble insulin (Actrapid)
–Humalog (insulin lipro), Novorapid (insulin aspart): rapid acting

Answer 13

Rapid onset, short duration of action
Have before a meal

Soluble insulin (Actrapid)
Humalog (insulin lispro)
Novorapid (insulin aspart): rapid acting

Question 14

What type of insulin is Soluble insulin (Actrapid)?

Answer 14

bolus insulin
when soluble natural insulin is given SC, it forms a hexamer under the skin (C peptide is cleaved, and A and B chain stick together)
This delays release so insulin must be injected 30 minutes before meals. If you eat quicker than this, the blood glucose control is bad.

Question 15

What type of insulin is Humalog? Describe the composition.

Answer 15

Bolus insulin
insulin analogue
Also called insulin lispro
as swap lysine and proline of insulin
makes insulin more rapid acting as no longer forms a hexamer
can have JUST before a meal (don’t have to wait 30 mins)

Question 16

What type of insulin is Novorapid? Describe the composition.

Answer 16

Bolus insulin
insulin analogue
Also called insulin aspart
as swap aspartate and proline of insulin
makes insulin more rapid acting
can have JUST before a meal (don’t have to wait 30 mins)

Question 17

What are the advantages/disadvantages of soluble insulin vs. Humalog and Novorapid?

Answer 17

Soluble insulin is half cost of the short acting insulin analogues (Novorapid and Humalog)
BUT soluble insulin has slower onset of action, so have to wait longer after injection before you can have a meal, in comparison to short acting insulin analogues

Question 18

What are the side effects of taking insulin?

Answer 18

• Hypoglycaemia
• Weight gain
• If you drive HGV, cannot work

Question 19

From what source can GLP-1 be extracted?

Answer 19

Gila monster (lizard) makes a venom called exendin 4
Similar to GLP1
GLP-1 is an Incretin (enhances glucose stimulation insulin release)

Question 20

What stimulate GLP-1 release?

Where is GLP-1 release from?

Answer 20

Ingestion of food

GI tract stimulated to release uncertain gut hormones: active GLP-1 and GIP

Question 21

What is the function of GLP-1?

Answer 21

glucose dependant insulin release from pancreatic beta cells -> insulin release increases peripheral glucose uptake
decreases glucose dependant glucagon release from pancreatic alpha cells -> increased insulin and decreased glucagon reduce HGO

thus leading to blood glucose control

Question 22

Name other effects of GLP-1

Answer 22

slows gastric emptying

reduces appetite (and helps weight loss)

both GOOD FOR PATIENTS!

Question 23

SGLT-2 inhibitors

Answer 23

Describe the MOA of SGLT-2 inhibitors.

sodium-glucose co-transporter 2

Question 24

Describe the MOA of SGLT-2 inhibitors.

sodium-glucose co-transporter 2

Answer 24

glucose filtered into urine in renal glomerulus
glucose is reabsorbed in proximal tubules through SGLT-2 (and less by SGLT-1) co transporters] Hence normal person will have little glucose in urine as most is reabsorbed by SGLT-2 (90%) transporters
Hence SGLT-2 inhibitor stop glucose reabsorption and increased glucose excretion in the urine

Question 25

What are the side effects of SGLT-2 Inhibitors?

Answer 25

Hypoglycaemia (in combination with insulin or  SUs)
Urogenital infections (vulvovaginal candidiasis, UTI, balanitis)