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 


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

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

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 damageLFTs 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

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
  • MechanismIncrease 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

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

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
  • MechanismInhibit 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

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

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

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

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

Bariatric surgery
  • Consider with BMI >35kg/m2  with poorly controlled diabetes
Advantages
Disadvantages
Works in controlling glycaemia and weight Costly
Long-term complications – osteoporosis, vitamin deficiencies, potential hypoglycaemia due to excess insulin
Requires lifelong support and monitoring