Treatment of Diabetes

Question 1

What are the main ways that insulin is produced

Answer 1

Animal procine or animal bovine

Human recombinant

Insulin analogues - where one or two amino acids in an insulin molecule have been changed which allows the modification of the pharmacokinetic properties

Question 2

Name the 6 main insulin catagories and drug examples of each

Answer 2

Ultrafast acting

Rapid acting - Nororapid

Short acting - Actrapid, Humulin S

Intermediate acting - isophane insulin. Given overnight to prevent hyperglycaemia

Long acting and very long acting - insulin degludec, insulin glargine. Allow low level of insulin in body

Question 3

Name some adverse effects of insulin therapy

Answer 3

Hypoglycaemia

Hyperglycaemia

Lipodystrophy - lipohypertrophy or lipoatrophy

Painful injections

Insulin allergies - mainly to preservatives

Question 4

Name some drugs that are used in the treatment of type 2 diabetes

Answer 4

Metformin (biguanides)

Sulphonylureas

Thiazolidinediones - pioglitazone

DPP4 inhibitors

Gliflozins (SGLT2s)

GLP1 analogues - exenatide, liraglutide

Question 5

What is the target HbA1c level for type 2 diabetics

Answer 5

HbA1c of 6.5 to 7.5%

Question 6

Describe how metformin works

Answer 6

Decreased insulin resistance -> increased glucose uptake by tissues

Decreased hepatic glucose production

Limits weight gain

Decreased risk of CVS events

Question 7

Name some side effects of metformin treatment

Answer 7

GI symtpoms

Vit B12 deficiency

Lactic acidosis - rare

Question 8

Describe how sulphonylureas work and what their side effects are

Answer 8

Sulphonylureas stimulate beta-cells to release insulin

They decrease microvascular risks associated with diabetes

Side effects: weight gain and hypoglycaemia

Question 9

Name some sulphonylureas

Answer 9

Gliclazide

Question 10

Describe how thiazolidinediones work in treating diabetes

Answer 10

Thiazolidinediones increase insulin sensitivity in muscle and aidpose and decrease hepatic glucose output

They bind to and activate PPARs

Are rarely used - used in combination with other agents

Question 11

Name a thiazolidinedione and what the concerns regarding its use are

Answer 11

Pioglitazone

Concerns regarding weight gain, fluid retention and HF. Risk of bladder cancer

Question 12

Describe how gliflozins work

Answer 12

Gliflozins selectively inhibit SGLT2 in the PCT to inhibit glucose reabsorption in the PCT and so increase glucose excretion

Can be used as an add on

Question 13

How does GLP-1 help to treat diabetes

Answer 13

GLP-1 is released from intestinal L-cells and causes:

• Increased insulin and decreased glucagon secretion
• Increased sateity
• Decreased gastric emptying
• Increased glucose uptake by muscles
• Decreased glucose production by the liver

Question 14

Name some GLP-1 agonists

Answer 14

Exenatide

Liraglutide

Lixisenatide

Question 15

Name some ADRs with the use of GLP-1 agonists

Answer 15

GI symptoms - nausea, loose stools, diarrhoea, gastroesophageal reflux

Painful injection

Risk of pancreatitis and pancreatic carcinoma though NICE and FDA found no evidence of pancreatitis

Question 16

Describe how gliptins/DPP4 inhibitors work and what their side effects are

Answer 16

DPP4 antagonists inhibt DPP4 activity to increase post-prandial active GLP-1 concentrations

Side effects include GI symptoms and pancreatitis. Low risk of hypoglycaemia

E.g. sitagliptin, vildagliptin, linagliptin