Let’s start this one with a question…
What do thiazolidinediones, DPP4 inhibitors, acarbose, SGLT2 inhibitors, sulphonylureas, GLP1-agonists, metformin, gliptins, and glitazones all have in common? Yep, they all have stupid names.
I remember an old saying – “If there are many ways to treat something it is likely none of them are the best”.
The amount of Type 2 diabetic oral or injectable hypoglycaemic agents (even that is a mouthful) on the market has now become amazingly broad.
As we all know, diabetes is one of the greatest challenges to modern healthcare, and yes, we do need to lower people’s sugars to help prevent the macro and micro vascular complications of prolonged hyperglycaemia – (though even the macro benefits are still under debate!).
So here it is. I have put together a basic summary of each agent and its current recommendations from Diabetes Australia and a large pool of other references.
My tip is to use it as a reference. If you are studying, just focus on the summary “Key points to remember” column.
The table is my own research. If there are details that I have left out then please let me know. I hope to have this as an evolving table which will change and improve over time as new data becomes available.
Conflicts of Interest – None! – Let me make it clear I get no money from anyone (other than my patients when I treat them). My only interest in this topic is getting the best outcome for my patients (and hopefully help clarify some of the information for other doctors in Australia!)
A few other useful diabetic items
Brilliant websites for resources and information
RACGP Handbook (getting bit big for the hand though…) – Link
Diabetes Australia – Link
Australian Diabetes Council – Link
National Diabetes Services Scheme (NDSS) – Link
Abbreviated stepwise approach to T2DM in Australia – Flow diagram for diagnosis Link (based on T2DM handbook RACGP)
- Screen patients who come in (some are obvious, others you can use the AusDRISK scoring survey – (Link))
- Send them for fasting BSL. If > 7 then repeat again. If >7 again then T2DM! If fasting BSL between 5.5-6.9 then off for a fasting Glucose Tolerance Test (GTT). (Can we use HbA1c? Currently not funded – but info on the flow diagram above…)
- If fasting GTT > 11 at 2 hrs (or >7 fasting) then T2DM!
- Then you do a lot of counselling and education etc (info sheets here – Link). Organise your GP Management Plan and Team Care Arrangement (Link) and Diabetes cycle of care (Link)
- Then you do your Hba1c and tests (An example from Tassie – Link). Can do lifestyle management for 3 mths if borderline. Consider medication in very high Hba1c (>7 or depends on patient).
- Aim target of Hba1c (controversial) – approx <7% but depends on patient. (link)
- Start medication – Metformin is FIRST LINE. Therapeutic guidelines suggests starting at 500mg BD with food. Can titrate up to 3g/day (1g TDS).
- Second line?? Have a look at this flow chart (link) and the table below. Usually start the medication and then review 3mthly including follow up testing and examinations (as per above cycle of care)
Mode of Action – Physiology Refresher
- Decreases gluconeogenesis of the liver
- Increases glucose uptake at muscle.
- Increases insulin sensitivity in the liver
- Causes an increased release of insulin from the pancreas
- Increases insulin sensitivity
- These BLOCK reuptake of glucose by the nephron and therefore you urinate out the extra glucose
- Inhibits enzymes required to digest carbohydrates
DPP4 Inhibitors: (Remember this is ONE STEP BEFORE GLP1 agonists – Byetta – so remember them together!)
- Glucagon increases blood glucose –> DPP4 inhibitors increase incretin. Incretin BLOCKS glucagon release and increases insulin release. This DECREASES blood glucose.
Combination drugs available that I could find:
- Avandamet = Rosiglitazone + Metformin
- Galvumet = Vildagliptin + Metformin
- Glucovance = Glibenclamide + Metformin
- Janumet XR = Sitagliptin + Metformin
- Kombiglyze XR = Saxagliptin + Metformin
- Nesina Met = Alogliptin + Metformin
- Trajentamet = Linagliptin + Metformin
Finally, PBS prescribing restrictions.
I have summarised it because the proper ones are very detailed. The original PBS restrictions are here – Link
SUMMARY of PBS restrictions for second line medications (other than sulfonylureas) (they are all SLIGHTLY different so see full details on PBS website – Link).
Generally, you will need these to use a second line agent funded by PBS (other than a sulfonylurea)
- Must be used either with Metformin OR Sulfonylurea,
- Must have a contraindication or intolerance to combination of Meformin and Sulfonylurea
- Must have HbA1c measurement >7%, within the last 4mths, PRIOR to intiation despite treatment with metformin or sulfonylurea AND you must write this in the notes
Rob’s Diabetes Type Two cents worth…
So the options available are broad; but lets narrow things down. Metformin is first line. I will titrate this up to control Hba1c USUALLY below 7% (If they are elderly, or have other medical comorbidities I may have a target a little higher than this – I will discuss it with my patient). If I cannot get control of their Hba1c then I will consider starting Sulfonylurea as per the PBS guidelines. If my patient in intolerant of sulfonylureas or there are contraindications (eg. the patient is elderly and hypoglycaemia could be dangerous, or the patient is significantly worried about the possibility of gaining weight) then I will look at other second line agents.
I cannot tell you which one to use. My basic suggestion, however, would be to look at your usual demographic of patients and get experience and learn about one or two agents. For example, if most of your patients are postmenopausal women at high risk of vaginal infections then don’t spend alot of time learning about SGLT2 inhibitors.
If your demographic has alot of GI issues (a large proportion of IBS patients) then perhaps learning all about acarbose would not be so useful.
Either way, I would get used to one or two agents and know the ins and outs of these. Have your own framework in your head about how you will titrate up therapy (RACGP loves this sort of stuff in fellowship exams).
Remember, if you are on two maximal agents and Hba1c is still > 7% you might want to start discussions about basal insulin.
Good luck. Use the above resources wisely and never forget to consider if your medication plan is not working – check to see how, and if, the patient is taking the medication you have prescribed!
* Top picture from: Link