New diabetic drugs

Question 1

Which drugs are used in management of hyperglycaemia

Answer 1

Diet and exercise
Biguanide (Metformin)

Sulphonylureas (eg gliclazide)

Insulin sensitisers : thiozolidinediones such as rosiglitazone or pioglitazone

Insulin itself (there are several new insulin analogues now available)
I
ncretins (GLP-1 analogues)

Gliptins (Dipeptidyl peptidase 4 inhibitors).

Question 2

T/F Insulin is a useful treatment in T2DM

Answer 2

T

Insulin is an excellent treatment, even for patients who are not dependent on it (NIDDM)

Question 3

What is the treatment regime for those using insulin in T2DM

Answer 3

Patients need a long acting (depot) insulin

Together with a short acting insulin such as normal soluble insulin with each meal

Question 4

Give an example of long acting and short acting insulin

Answer 4

Long: insulin Zinc suspension and glargine (lantus)

Short: “Insulatard” and “Actrapid”

Question 5

What is the problem with insulin use in T2DM

Answer 5

When soluble natural insulin is given subcutaneously, it forms a hexamer under the skin

This delays release

so people must

“Inject 30 mins before meals”.

Question 6

How can the issue of having to inject insulin 30 minutes before meals be overcome

Answer 6

You can use insulin analogues.

Lispro switch of B28 (Pro)/B29 (Lys)

Aspart switch (Pro 28) to Asp (28)

These analogues are very rapid acting and mean that patients can inject and eat.

Question 7

How are the benefits and disadvantage of short actin insulin analogues compared with insuln

Answer 7

:D Gives patients a licence to inject immediately before meals (many patients were injecting immediately before the meal when on the old insulins anyway, despite them needing 30 minutes to work)

:D Profile more closely mimics insulin profile following a meal.

:C Twice the cost of soluble insulin

Question 8

How are long acting insulin analogues used

Answer 8

Different alterations in the molecule to try and attain a plateau like concentration over time.

Question 9

What is glargine

Answer 9

A long acting insulin that seems to give the least variation in plasma insulin levels for 24 h after injection.

Previous long acting insulins were Zn suspensions of insulin. Efficacy slowly waned over 24 h.

Question 10

How is the molecular structure of glargine changed compared to insulin

Answer 10

A21 (Asn to Gly)

B31, B32 Arg

Question 11

Advantage and disadvantage of insulin glargine

Answer 11

Main advance is that this once daily insulin injection improves quality of life as there lower risk of hypoglycaemia.

Gives background concentration of insulin.

Normal pancreas makes continuous secretion of insulin.

Question 12

What is detemir

Answer 12

14 carbon fatty acid chain attached to B29.

Delayed onset 7h

Can be used as part of basal bolus.

Question 13

What are the advantages of insulin

Answer 13

Can give best control of HbA1c when combined with diet and exercise.

No side effects compared to metformin, SU, thiazolidinediones

Question 14

What are the side effects associated with the following diabetic drugs:

metformin,
SU,
thiazolidinediones

Answer 14

metformin (diarrhoea)

SU (occasional reactions)

thiazolidinediones (rare hepatic, ?osteoporosis)

Question 15

Which thiazolidinedione has been withdrawn and which is still used?

out of: Rosiglitazone and Pioglitazone

Answer 15

Rosiglitazone is withdrawn, Pioglitazone still in use

Question 16

Why was Rosiglitazone withdrawn

Answer 16

Over heart fears (linked to fluid retention and increased risk of heart failure)

Question 17

Disadvantage of insulin

Answer 17

Hypos, weight gain, increases hunger, If you drive HGV, cannot work, Increased insulin as a consequence
Huge doses required

Question 18

Why does one gain weight with insulin

Answer 18

Poor control enables one to lose weight.

If glycosuria stops, many calories saved.

Increased appetite

Improved well being

Set point of body weight (hypothalamic)

Question 19

What is GLP-1 and what are the physiological actions

Answer 19

GLP-1 is secreted from the gut, and signals the pancreas to make even more insulin.

Also directly affects appetite and gastric emptying

Question 20

Give an example of a GLP-1 analogue

Answer 20

Exanatide

Question 21

How do incretins work

Answer 21

Ingestion of food

Release of incretin gut hormones (GLP-1 and GIP)

Increase insulin release from beta cells (glucose dependent)- both GLP1 and GIP

Reduced glucagon release from alpha cells (glucose dependent)- just GLP1

Question 22

Other effects of GLP-1 other than insulin release

Answer 22

Reduces gastric emptying

Increases hypothalamic satiety.

(directly on hypothalamic GLP-1 receptors).

Question 23

T/F Exenatide also increases hypothalamic satiety

Answer 23

Yes, like GLP-1 it does do this

Question 24

What does DPP-4 do physiologically… what are the drug analogues called

Answer 24

DPP-4 enzyme rapidly degrades incretins

DPP4 analogues known as gliptins

Question 25

What is the downside of incretin

Answer 25

this is an injection

Question 26

Name of some gliptins

Answer 26

vildagliptin and sitagliptin

Question 27

Names of GLP-1 analogues

Answer 27

Exanatide
Liraglutide (Victoza or Saxenda)
Semaglutide

Question 28

Are GLP-1 analogues and gliptins useful for management of diabetes?

Answer 28

Both seem effective strategies in weight reduction in type 2 DM

Question 29

What is the normal plasma glucose concentration

Answer 29

5-5.5mmol/L

Question 30

How much plasma is filtered per day

Answer 30

180L/day

Question 31

How much glucose is filtered and reabsorbed per day

How much is excreted?

Answer 31

160–180 g/day filtered
160–180 g/day reabsorbed

MINIMAL excreted

Question 32

How is glucose reabsorbed from the tubules

Answer 32

It should be noted that almost all of the glucose filtered by the glomerulus is reabsorbed in the proximal tubule, predominantly by SGLT2