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Stage 2: Inflammation > Type 2 Diabetes Medication > Flashcards

Type 2 Diabetes Medication Flashcards

1
Q

What are the 5 most used medications in T2D?

A

1) Biguanides e.g. metformin
2) Incretins - GLP-1 agonists
3) Dipeptidylpeptidase 4 (DPP4) inhibitors
4) S(odium)GLT2 inhibitors
5) Sulphonylureas

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2
Q

What are the 5 less commonly used medications in T2D?

A

1) Meglitinides
2) Thiazolidinediones
3) alpha-Glucosidase inhibitors
4) Amylin analogues
5) Insulin

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3
Q

Why has the use of insulin increased in T2D?

A

Bc people are living longer with T2D into later stages

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4
Q

Release of which substances that affect diabetes is not affected by metformin?

A

Insulin, glucagon, GH, cortisol, somatostatin

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5
Q

Describe metformin

A
  • Absorbed in small intestine
  • Half life = 3 hours
  • Not bound to plasma protein
  • Excreted unchanged in urine so no problem in people with kidney problems
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6
Q

What are the 7 ways that metformin decreases blood glucose concentration?

A

1) Decreased hepatic glucose production (gluconeogenesis)
2) Potentiates insulin action on muscle and adipose
3) Stimulates glycolysis in tissues and glucose uptake
4) Decreases carb absorption
5) Stimulates lactate production
6) Decreases LDL and VLDL
7) Inhibits expression of genes involved in gluconeogenesis
8) Increased GLP-1 release from intestines

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7
Q

What does metformin do?

A

1) Reduces HbA1c

- Does NOT cause hypoglycaemia, stimulate appetite or cause weight gain

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8
Q

What are the side effects of metformin?

A

1) Diarrhoea, nausea and metallic taste
2) Decreases intestinal absorption of folate and vitamin B12
3) Rare lactate acidosis

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9
Q

What is the first line medication in overweight/obese patients?

A

Metformin

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10
Q

What drugs can be given alongside metformin?

A

1) Thiazolidinediones
2) Incretins - GLP-1 agonists
3) Dipeptidylpeptidase 4 (DPP4) inhibitors
4) S(odium)GLT2 inhibitors
5) Sulphonylureas
6) Insulin

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11
Q

Which T2D drugs cause hypoglycaemia?

A

1) Sulphonylureas
2) Thiazolidinediones
3) insulin

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12
Q

What are the long term effects of metformin?

A

Reduces microvascular and macrovascular complications

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13
Q

Why does oral glucose cause more insulin release than a glucose infusion?

A

Due to the release of gut peptides

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14
Q

What is an incretin?

A
  • Gut derived factor which increases insulin release in response to glucose
  • As glucose levels go down, their effect decreases, so doesn’t cause hypoglycaemia
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15
Q

What are the two types of incretin?

A

1) Glucagon like peptide 1 (GLP1) - L cells in distal ileum

2) Gastric inhibitory peptide (GIP) - K cells in duodenum

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16
Q

What drug mimics incretins?

A

GLP-1 agonists (exenatide) - bind to GLP-1 receptor

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17
Q

How do GLP-1 agonists work?

A

1) Stimulates insulin release dependent on glucose (no effect if glucose is low)
2) Suppresses glucagon secretion (effect on alpha cells)
3) Reduces appetite and body weight (effect in brain)
4) Slows gastric emptying
5) Stimulated beta cell number

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18
Q

What are the effects of GLP-1 agonists?

A

1) Reduces HbA1c
2) Reduces weight
3) Evidence of CV benefit, decreased likelihood of CV complications
- Do not cause hypoglycaemia bc their action is glucose dependent

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19
Q

What are the side effects of GLP-1?

A

1) N&V
2) Constipation/diarrhoea (gut problems)
3) Headache
4) Rare acute pancreatitis

20
Q

Describe the metabolism of GLP-1

A
  • Has a short half life
  • 7-36 is the active part which activate GLP-1, rapidly broken down by DPP4
  • If activate DPP4 (using DPP4 inhibitor) you prolong half life of GLP-1 and its action
21
Q

How are GLP-1 agonists administered and why?

A

S/c injection (protein)

22
Q

How are (serine protease) dipeptidylpeptidase 4 (DPP4) inhibitors administered?

A

Orally

23
Q

What is an example of a DPP4 inhibitor?

A

Sitagliptin (end in gliptin)

24
Q

What drug are DPP4 inhibitors often given with (combined in one drug)?

A

Metformin (or SGLUT2 inhibitor)

25
Q

What are the effects of DPP4 inhibitors?

A

1) Reduce HbA1c

- No hypoglycaemia and no effect on weight

26
Q

What are possible side effects of DPP4 inhibitors?

A

1) Increase incidence of some cancers

2) Acute pancreatitis

27
Q

How do SGLT2 inhibitors work?

A
  • Inhibit glucose re-uptake in the kidney by inhibiting SGLT2 in PCT
  • Therefore more glucose is excreted and less is reabsorbed
  • Up to 10% excretion of calorie intake
28
Q

What is an example of an SGLT2 inhibitor?

A

Dapagliflozin (end in gliflozin)

29
Q

What drug are SGLT2 inhibitors often given with (combined in one drug)?

A

Metformin (or DPP4 inhibitor)

30
Q

How is metformin given?

A

Orally

31
Q

How are DPP4 inhibitors given?

A

Orally

32
Q

What are the effects of SGLUT2 inhibitors?

A

1) Reduces HbA1c
2) Reduces weight due to increased excretion of glucose
3) Evidence of CV (heart failure) benefit and renal benefit
- Does not cause hypoglycaemia

33
Q

What are the side effects of SGLUT2 inhibitors?

A

1) Polyuria
2) Dehydration - less water reabsorbed (follows glucose excreted)
3) Urinary disorders (UTI) bc more glucose in urine for bacteria
4) DKA

34
Q

How do sulfonylureas work?

A

1) Bind to sulfonylurea binding site on K channel in beta cell, mimicking increase in ATP (due to increase in glucose), closing K channel
2) This increases depolarisation leading to increased calcium and increased insulin release

35
Q

What is necessary to use sulfonylureas?

A

Some residual pancreatic beta-cell activity bc they act mainly by augmenting insulin secretion

36
Q

What are examples of sulfonylureas?

A

1) Gliclazide
2) Glipizide
3) Glibenclamide
4) Glimepiride

37
Q

What do sulfonylureas do in acute hyperglycaemia?

A

1) Increase insulin release
2) Increase plasma insulin concentration
3) Decrease hepatic clearance

38
Q

What happens to sulfonylureas in chronic hyperglycaemia?

A

1) No acute increase in insulin BUT decreased plasma glucose concentration still remains
2) Chronic hyperglycaemia decreases insulin release
3) Down regulation of sulfonylurea receptor
4) Largely protein bound (90-99%)

39
Q

What are the drug interactions of sulfonylureas (in chronic hyperglycaemia?)?

A
  • NSAIDS
  • MAO inhibitor
  • Some antibiotics
40
Q

What does the fact that sulfonylureas are excreted in the urine mean?

A

They have an enhanced effect in elderly and those with renal disease

41
Q

Describe 2nd generation sulfonylureas

A
  • Short half life 7-10h
  • 100x more potent than 1st generation
  • Last for 16-24 hours
  • Less interactions bc use lower concentrations
42
Q

What are the effects of sulfonylureas?

A

1) Reduces HbA1c

- DOES cause hypoglycaemia

43
Q

What is the side effect of sulfonylureas?

A

Weight gain (increases food intake)

44
Q

What is the target HbA1c% in T2D medication therapy?

A

< 7%

45
Q

What are the first two drugs tried in T2D?

A

Metformin + sulfonylureas

46
Q

How are sulfonylureas given?

A

Orally

47
Q

What is diet treatment in T2D?

A

Decrease intake of carbohydrate

Stage 2: Inflammation (39 decks)

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