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For more than 60 years we’ve had two kinds of tablets that lower blood glucose levels: metformin and the sulphonylureas. Metformin works by increasing the effect of insulin in the liver and muscle, while the sulphonylureas work by increasing the amount of insulin produced by the pancreas.

The other glucose-lowering tablets are more recent and work by slowing carbohydrate absorption (acarbose), increasing the effect of insulin (metformin), increasing
glucose uptake in the muscles (glitazones) or by increasing the amount of glucagon-like peptide (GLP) that increases insulin levels (like the sulphonylureas) but also lowers the amount glucagon that increases glucose levels.

These tablets target four organs: the gut, pancreas, liver and muscle. There is now another type of glucose-lowering tablet, which targets the kidneys: the gliflozins, dapa and canagliflozin.

How gliflozins work
Although often underappreciated, the kidneys have important actions: working with the liver to increase blood glucose levels (BGLs) when blood glucose is low (hypoglycaemia), breaking down insulin and many medicines and controlling the filtering and reabsorption of large amounts of glucose.

In someone with an average BGL of 8 mmol/L, the kidney filters more than 100 L of fluid containing 800 mmol (144g) of glucose each day. The kidney reabsorbs most of the
glucose (124 g), with 20 g leaving the body in the urine. This loss of glucose is called glycosuria and was tested by people as an indicator of blood glucose control before blood glucose monitoring became practical in the 1980s.

The kidneys have special mechanisms to reabsorb the filtered glucose and the gliflozins affect these to decrease reabsorption. A lot more glucose is lost in the urine each day, e.g. 100 g instead of 20 g. This lowers BGLs and also the amount of energy stored in the body for everyday use (100 g of glucose can produce 1600 kJ of energy).

Are gliflozins right for you?
Gliflozins’ effects sound pretty good but, as with all medication, there are potential problems. Probably because of the extra amount of glucose in the urine, the risk of genital and/or urinary tract infection increases (particularly for women). Usually these infections are mild and easily treated but occasionally mean that gliflozins can’t be used.

Currently gliflozins are only recommended for type 2 diabetes and are subsidised by the Pharmaceutical Benefits Scheme (PBS) under certain circumstances. If you’re
interested in finding out more about gliflozins, ask your doctor or visit the

Dr Pat Phillips MBBS, MA, FRACP, MRACMA, is Editor-in- Chief of Conquest and Past Director of the Diabetes Centre and Endocrinology, Queen Elizabeth Hospital & Health
Service.

This article was originally published in Conquest magazine published by Health Publishing Australia