Diabetes Medication Flashcards by Martha Innes

What is the mechanism of metformin?

Inhibits the mitochondrial respiratory chain to cause a decrease in ATP which decreases hepatic glucose production to lower glucose levels
Increases gut glucose utilisation and metabolism

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Where does metformin act?

Hydrophilic so requires active transport by organic cation transporters to be taken into the intestines, liver and kidney

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Is metformin insulin dependent or independent?

Insulin independent

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What are the clinical benefits of metformin?

Lowers glucose levels
Weight neutral or negative
Cheap

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What is the usual dose of metformin?

500mg bd

Max dose 1g bd

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What are the side effects of metformin?

GI intolerance (diarrhoea, bloating, abode pain, dyspepsia, metallic taste in mouth)
Metformin associated lactic acidosis

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What should be done if a patient on metformin has GI side effects?

Reduce to 500mg od and increase slowly

Or use a modified release formulation

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What should be done if a patient on metformin develops metformin associated lactic acidosis?

Max dose 1g daily if eGFR <45

Metformin contraindicated if eGFR <30

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Does metformin have an effect on CVD?

Large sustained benefit on CV mortality

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When is metformin prescribed?

First line for all diabetic patients

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What are examples of sulphonylureas?

Gliclazide (most common)

Glipizide

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What is the mechanism of action of sulphonylureas?

Bind to KATP channels of pancreatic beta cells, causing channels to close
This causes depolarisation, calcium channels open and insulin secretion increases

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Is the mechanism of sulphonylureas glucose independent or dependent?

Independent - can cause insulin secretion even when glucose is not increased

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What type of drug are sulphonylureas?

Insulin secretagogues

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What are the clinical benefits of sulphonylureas?

Potent glucose lowering

Cheap

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What are the side effects of sulphonylureas?

Increased risk of hypoglycaemia

Weight gain

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Do sulphonylureas have an effect on CVD?

May increase risk but unsure, doesn’t decrease risk

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Which patients are most at risk of hypoglycaemia on sulphonylureas?

Elderly
Patients who have had diabetes for a long time
High creatine
Lower HbA1c (esp <50mmol/mol)

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For which occupations would hypoglycaemia be a risk?

Driving

Working up ladders

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When are sulphonylureas prescribed?

2nd line after metformin, especially if cost is a major consideration

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What is the mechanism of thiazolidinediones (TZDs)

Act mainly on adipocytes to increase differentiation from pre-adipocytes to mature adipocytes, increasing subcutaneous fat mass by taking fat from liver and muscle to reduce lipo-toxicity
This increases insulin sensitivity

What are examples of TZDs?

Pioglitazones

What are the clinical benefits of TZDs?

Reduce glucose levels
Especially potent in obese women
Reduce blood pressure
Very cheap

What are the side effects of TZDs?

Weight gain
Fluid retention (peripheral oedema)
Increase in risk of cardiac failure (but risk is v low in young people so doesn’t make much difference)
Fracture risk

Do TZDs have an effect on CVD?

Probably reduces CV risk

When are TZDs prescribed?

2nd line where cost is a major consideration or if there is a need to minimise hypoglycaemia Not used in over 65s or patients with heart problems Best for younger, obese, insulin resistance patients

Which drugs use the incretin effect?

DPP4 inhibitors | GLP-1 receptor agonists

What is the incretin effect?

Insulin secretion is higher after oral glucose than after IV glucose This is because substances called incretins are released when glucose is absorbed in the gut Incretins increase insulin secretion

What are examples of incretins?

GIP | GLP-1

What are incretins broken down by?

DPP4

How do incretins increase insulin secretion?

After the triggering pathway has started insulin secretion incretins act via G-protein coupled GLP-1/GIP receptors to increase cAMP This closes the KATP channel, increases calcium influx and increases insulin secretion

What is the benefit of incretin-like drugs compared to sulphonylureas?

Sulphonylureas can increase insulin even when there is no glucose leading to hypoglycaemia Incretin-like drugs can only act after glucose has initiated insulin secretion so do not cause hypoglycaemia

What is the mechanism of DPP4 inhibitors?

Inhibit breakdown of GLP-1 and GIP by inhibiting DPP4 | This augments the incretin effect and increases insulin secretion without causing hypoglycaemia

What are examples of DPP4 inhibitors?

Sitagliptin Alogliptin Saxagliptin

What are the clinical benefits of DPP4 inhibitors?

``` Glucose lowering (but weak) Weight neutral ```

What are the side effects of DPP4 inhibitors?

Minimal, generally well tolerated | Possible increased risk of pancreatitis

Do DPP4 inhibitors have an effect on CVD?

Unsure - mixed results

What is the mechanism of GLP-1 receptor agonists?

These are GLP-1 molecules modified to avoid breakdown by DPP4 Act in the same way as GLP-1 to increase insulin secretion Lower glucagon

What are the clinical benefits of GLP-1 receptor agonists?

Potent glucose reduction Weight loss Blood pressure reduction

What are the side effects of GLP-1 receptor agonists?

Nausea and vomiting (often improves after about 6 weeks) | Small increase in gallstones

Do GLP-1 receptor agonists have an effect on CVD?

Reduce risk

Do GLP-1 receptor agonists have an effect on renal disease?

Reduction in new onset macroalbuminmemia but no impact in eGFR decline

When are GLP-1 agonists prescribed?

Given with metformin for patients at high risk of CVD or kidney disease or for patients who want to lose weight

When are DPP4 inhibitors prescribed?

2nd line for people with no risk factors

What is the mechanism of SGLT2 inhibitors?

In most people glucose is filtered into kidney tubules and glucose transporters (SGLT) absorb all the glucose SGLT2 inhibitors decrease uptake of sugar and increase renal glucose loss - so basically make you pee sugar

What indirect effects do SGLT2 inhibitors have?

Glucose reduction Renal protection Reduction in insulin and increase in glucagon Increase in lipolysis, increase in free fatty acids, increase in ketone body production Cardiac benefit but can increase ketosis and risk of ketoacidosis

What are the clinical benefits of SGLT2 inhibitors?

Moderate efficacy | Blood pressure reduction

What are examples of SGLT2 inhibitors?

Dapagliflozin Canagliflozin Empagliflozin

What are the side effects of SGLT2 inhibitors?

Thrush - secondary to glycosuria Fournier gangrene Hypovolaemia and hypotension Diabetic ketoacidosis

Do SGLT2 inhibitors have an effect on CVD?

Large CV benefit

Do SGLT2 inhibitors have an effect on renal outcomes?

Beneficial effect

When are SGLT2 inhibitors prescribed?

2nd line for patients at high risk for CV or renal disesae