Antidiabetic Medications

• These are only really used in T2DM to control hyperglycaemia
  • Insulin is used in either very severe T2DM (at diagnosis) or longstanding T2DM
• In this section, we will go through how these are used and the advantages of disadvantages of each medication

This table summarises the key points for each of the medications 

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Overview

• There are 7 key medications used in T1DM. these are of different types:
  • Insulin Sensitisers
    • Biguanides (i.e. metformin) 
    • Pioglitazone
  • Insulin Secretagogues
    • Sulphonylureas 
  • Incretin modifiers
    • DPP4 inhibitors
    • GLP 1 analogues
  • Others
    • SGLT2 inhibitors 
    • Insulin

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METFORMIN

• Used as first line by default as it is effective, cheap, and has tolerable side effects
  • Dose – 500mg- 2000mg taken BD after meals
• Mechanism – increases sensitivity to insulin

 

• Side effects:
  • GI upset – Nausea, diarrhoea, abdo pain
  • Renal failure
  • Lactic acidosis – do not take if dehydration risk and seek assessment

• Contraindications:
  • GFR<30 – i.e. CKD stage 4
  • Tissue hypoxia conditions – worsens lactic acidosis. E.g. sepsis, MI
  • Stop before contrast media is injected
  • Stop before general anaesthetic

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Pioglitazone

• This is the only thiazolidinedione  that is currently used
  • Others were discontinued due to their side effects
• Effective but the side effects are severe
  • Good for South Asians and severe insulin-resistance in particular
    • Therefore fairly limited
  • Also used as 2nd line in patients with renal problems (where SGLT2, DPP4Is, and metformin would be contraindicated)
• Mechanism – increase insulin sensitivity – like metformin

• ADRs
  • Significant weight gain like SUs
  • Fluid retention causing oedema and heart failure
  • Can cause liver damage – LFTs must be done every 8 weeks for a year
  • Increases fracture risk via osteoporosis
  • Hypoglycaemia when combined with sulphonylureas/insulin – fine on its own

• Contraindications
  • Heart disease – IHD or CCF
  • Bladder cancer – regularly check haematuria
  • Risk of fractures – e.g. the elderly

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Sulphonylureas

• E.g. Gliclazide
• Now usage is less common due to more side effects compared to other therapies
  • However, it is 2nd line and used if it is suitable and no contraindications
  • Mainly used because it quickly controls glucose

• Mechanism – Increase insulin secretion

 

• Side effects:
  • Hypoglycaemia – Especially in the elderly or  renal impairment
  • Increase appetite => obesity. Therefore not recommended in overweight patients
  • Cardiovascular risks

• Contraindications:
  • Omitted on morning of surgery due to hypoglycaemia risk

• Sulphonylurea receptor binders
  • E.g. Repaglinide, Nateglinide
  • Rarely used in the UK
  • Mechanism
    • These are also insulin secretagogues
    • Rapid-acting therefore are very useful for taking with meals to reduce post-prandial hyperglycaemia
      • Very good for those with irregular mealtimes

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DPP4 Inhibitors

• AKA the Gliptins
  • E.g. Sitagliptin, Linagliptin

• These are new drugs
  • Highly effective, weight neutral and don’t cause hypose

• Indications
  • Often used as alternatives to insulin as they don’t cause hypose

• Mechanism – Inhibit the DPP4 enzyme which breaks down incretins.
  • This increases the availability of incretins
  • Incretins increase insulin release, reduce glucagon, and increase satiety
  • Therefore, indirectly increase post-prandial insulin release
    • They are therefore good for matching insulin to normal physiological requirements – thus preventing a hypose
  • Therefore also reduce appetite to reduce weight

• Adverse effects are minimal
  • GI upset – like metformin

• Contraindicated in:
  • Patients at risk of pancreatitis – therefore avoid if possible in GET SMASHED
  • If GFR <50 – except linagliptin

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SGLT2 inhibitors

• E.g. Dapagliflozin, canagliflozin, empagliflozin

• Very useful to control weight, BP, and glucose at the same time
  • Therefore linked with improved cardiovascular outcomes as well as Hba1c
  • These are relatively new drugs but very effective so predicted to increase use

• Mechanism – Inhibit SGLT2 in the kidney which reabsorbs glucose from the urine
  • Therefore induce glycosuria

• ADRs
  • Increased UTI risk
  • Hypotension risk

• Contraindications
  • Do not use with diuretics as it will cause hypoglycaemia
  • CI in Renal Impairment – GFR <45

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Acarbose

• Mechanism
  • Decreases breakdown of starch in the drug to glucose absorption in the gut

• Useful as an add-on therapy but often ineffective
  • Used if other therapies cant be used
  • Main side effect is flatulence

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Injections

• 2 types of subcutaneous injections are used in T1DM
  1. GLP1 analogues
  2. Insulin

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GLP1 analogues

• E.g. exenatide, liraglutide
  • These are given as a SC injection

• Mechanism
  • GLP1 are incretins that work by augmenting insulin release
  • Therefore work similarly to DPP4 inhibitors but are a lot more potent therefore used for poorly-controlled DM

• Indications
  • Very potent –  reducing HBa1c by >1%
  • Also useful in that they aid weight loss significantly
  • However they are expensive and of course an injection therefore somewhat limited
    • However, some such as exenatide can be given just once a week

• ADRs
  • Not really any major effects
  • Contraindications
    • Avoid if GFR <30

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Insulin in Type 2 DM

• DM2 patients still have a degree of impaired B cell function especially in advanced disease
  • Insulin is useful in these patients

• Indications for starting insulin in T2DM:
  • Typically used as the disease progresses and the patient has already been on oral agents
  • However, if the patient is highly symptomatic/has a very high Hba1c then it may be started 1st line without oral agents

• See insulin therapy for more details on insulin

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Bariatric surgery

• Consider with BMI >35kg/m2  with poorly controlled diabetes