Management of type 2 DM Flashcards by Heo Mun Ho

What a diabetic should expect from care from their MDT (11)

BG monitoring
BP monitoring
Cholesterol monitoring
Eye screening
Foot screening
Kidney function monitoring
Weight monitoring
Smoking cessation support
Individual care plan
Education course about diabetes
Emotional + psychological support

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Drug types used to increase insulin release in type 2 (4)

Sulphonylureas - oral
Metiglinides - oral
Incretin mimetics aka GLP-1 analogues - injectable
DPPIV inhibitors - oral

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Drug type used to increase excretion of glucose in type 2 (1)

SGLT2 inhibitors

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Drug types used to improve insulin action (so increase glucose uptake) in type 2 (2)

+ non-pharmacological way of improving insulin action

Biguanides, e.g. metformin
Thiazolidinediones (or glitazones)

Weight reduction

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Target HbA1c level for both type 1 and 2

<48mmol/mol (6.5%)

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Target HbA1c for both type 1 and 2 is usually 48mmol/mol but for type 2’s prescribed on a single drug associated with hypoglycaemia (such as a sulphonylurea), or two or more antidiabetic drugs in combination should aim for what target

53 mmol/mol (7.0%)

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1st line treatment of type 2 DM/ initial treatment of type 2
+ what other option if contra-indicated/ not tolerated

Metformin

If contra-indicated
-sulfonylureas (Glimepiride, Gliclazide, Glipizide)

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When should drug treatment be intensified, alongside reinforcement of advice regarding diet, lifestyle, and adherence to drug treatment in type 2 diabetics

If HbA1c concentrations are poorly controlled despite treatment with a single drug (usually considered to be a rise of HbA1c to 58 mmol/mol (7.5%) or higher)

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If 1st line treatment doesn’t control HbA1C adequately, what are the 2nd line options (i.e. what is added to 1st line treatment) (any of 4)

Metformin
+

sulfonylurea
or
thiazolidinedione (or glitazone)
or
dipeptidylpeptidase-4 (DPP-IV) inhibitor
or
sodium glucose co-transporter 2 (SGLT-2) inhibitor

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If 2nd line treatment doesn’t control HbA1C adequately, what are the 3rd line options (i.e what is added to the 1st and 2nd line treatment) (any of 3 oral options or 2 injectable options)

Metformin
+
2nd line (usually sulfonylurea)
+

thiazolidinedione (or glitazone)
or
dipeptidylpeptidase-4 (DPP-IV) inhibitor
or
sodium glucose co-transporter 2 (SGLT-2) inhibitor

or
insulin
GLP-1 agonist

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Name some sulfonylureas

Glimepride

Gliclazide

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Name a thiazolidineodione

Pioglitazone

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Name a dipeptidylpeptidase-4 (DPP-IV) inhibitor (‘gliptins’)

Sitagliptin

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Name a sodium glucose co-transporter 2 (SGLT-2) inhibitor (‘gliflozins’)

empaglifiozin

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Mechanisms of action of metformin (3)

Reduces amount of glucose produced by liver
-inhibits gluconeogenesis

Improves insulin sensitivity of muscle tissue to increase glucose uptake

Improves glucose transport

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Advantages of metformin (5)

Doesn’t cause weight gain

Cheap

Well tolerated

Doesn’t stimulate insulin secretion so doesn’t trigger hypoglycaemia alone

Reduces risk of microvascular complications

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Common side effects of metformin (5)

Nausea
Vomiting
Diarrhoea
Abdo pain
Decreased appetite

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Rare side effect of metformin

Lactic acidosis

-due to it inhibiting lactic acid uptake by liver

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Mechanism of action of sulphonylureas

Bind to sulfonylurea receptors on functioning beta cells in pancreas to stimulate increased insulin release

binding closes ATP sensitive potassium channels linked to the receptor
so decreased potassium entering cell, leads to depolarisation of cell membrane
voltage dependent Ca2+ channels open resulting in influx of Ca2+ and subsequent Ca2+ dependent exocytosis of insulin vesicles

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Side effects of sulphonylureas (5)

Weight gain
Abdominal pain; 
diarrhoea; 
hypoglycaemia; 
nausea

Contra-indications of sulphonylureas (2)

Pregnancy

Breast feeding

Mechanism of action of thiazolidinediones (glitazones)

Reduces insulin resistance (improves insulin sensitivity) in liver and peripheral tissue, allowing the insulin that the body produces to work more effectively

Contraindications of thiazolidinediones (glitazones) (5)

Heart failure
Bladder cancer
Hepatic impairment
Pregnancy
Breastfeeding

Side effects of pioglitazone (a thiazolidinedione) (5)

Bone fracture - esp women
increased risk of infection;
numbness; 
visual impairment; 
weight gain

What are incretins

Hormones that stimulate a decrease in blood glucose levels Incretins are released after eating and increase the secretion of insulin

What is the incretin effect + what happens to this type 2 diabetics

defined as the increased stimulation of insulin secretion elicited by oral as compared with intravenous administration of glucose under similar plasma glucose levels. type 2 diabetics lose this incretin effect

Mechanism of action of DPP-IV inhibitors (gliptins)

DPP-IV is an enzyme that rapidly degrades incretins (natural hormones that stimulate insulin release) so inhibitors of this delay breakdown of incretins therefore increasing the time it is active, thus increasing insulin secretion

Advantages of DPP-IV inhibitors (3)

No risk of hypos Doesn't cause weight gain/loss Can be used in renal impairment; dose just needs to be adjusted

Need to be cautious with use of sulphonylureas if have (2)

renal impairment - reduce dose | hepatic impairment - reduce dose

Contraindications of DPP-IV inhibitors

Pregnancy | Breast feeding

Common side effect of DPP-IV inhibitors (sitagliptin) + uncommon side effect

Headache Pancreatitis

Name some incretin mimetics (GLP-1 (glucagon like peptide-1) analogues)

Lixisenatide | Exenatide

Mechanism of action of incretin mimetics (GLP-1 analogues) (3)

Binds to, and activates, the GLP-1 (glucagon-like peptide-1) receptor to increase insulin secretion, suppresses glucagon secretion, and slows gastric emptying Act like incretin and stimulate release of insulin Injectable analogues are resistant enzyme degradation so longer half life

Injectable incretin mimetics (GLP-1 analogues) only indicated if BMI greater than

30-35

Advantages of incretin mimetics (GLP-1 analogues) (2)

Weight loss | No risk of hypos

Side effects of incretin mimetics (GLP-1 analogues) (5)

``` Nausea Vomiting Appetite loss --> weight loss diarrhoea headache risk of pancreatitis ```

Contraindications of incretin mimetics (GLP-1 analogues)

Pregnancy | Breastfeeding

Which drug class used to treat type 2 DM has a completely different mechanism of action than all other agents

SGLT2 inhibitors

Majority of glucose is reabsorbed back into blood by what and where in the kidney

via SGLT2 transporter in proximal tubule of kidneys

Mechanism of action of SGLT2-inhibitors ('gliflozins')

Selectively inhibit SGLT2 transporter in the proximal tubule of the kidney so preventing glucose reabsorption therefore excreting more glucose in urine

Advantages of SGLT2 inhibitors (3)

Lowers HbA1C - good glycaemic control Weight loss No risk of hypos if used alone Lowers systolic BP

Side effects of SGLT2 inhibitors (5)

UTI Fungal infections Balanoposthitis - inflamed foreskin of penis Postural hypotension risk of hypos if used alongside insulin or sulphonylurea

Contraindications of SGLT2 inhibitors (4)

Pregnancy Breastfeeding Renal impairment, eGFR <60 Hepatic impairment

Insulin is indicated in type 2 DM when...

if they have osmotic symptoms and poor glycaemic control still despite being on other agents

When insulin is used in type 2 DM, it's supplementary (i.e. used alongside oral agents, never on its own), what type of insulin is usually used in type 2

Isophane insulin - intermediate acting | -once daily

Contraindication of metformin

if eGFR <30

Side effects of insulin

Hypos | Weight gain

If HbA1c levels are not adequately controlled by a single drug and rise to 58 mmol/mol (7.5%) or higher, what should be done

reinforce advice about diet, lifestyle and adherence to drug treatment intensify treatment

What factors should be managed first before choosing a glucose lowering drug (5)

``` Smoking BP Cholesterol Diet Exercise ```