A small drop in GFR (<30%) may occur within first 4-6 weeks of commencement. This should stabilise and is similar to that seen with ACE inhibitors. There is no evidence that eGFR measurement at an interval after initiation can identify patients who are intolerant and we do not recommend routine blood checks specifically to assess effect on GFR at this time point. Patients should undergo eGFR measurement at intervals based on their eGFR and at least annually. SGLT2 are potassium neutral. SGLT2i should be used with caution in the frail elderly due to the risk of intravascular volume depletion. SGLT2i are contraindicated in pregnancy and breast feeding.
Sick day guidance
Sick day guidance should be given when introducing these agents, with the aim of reiterating the advice when able. Provision of written advice regarding sick day rules is available. This is due to
increased risk of ketosis and is different to ‘sick day’ rules for other drugs e.g. ACE inhibitors. For patients on insulin treatment, additionally they should always be advised never to stop their
insulin as part of the sick day response.
SGLT2i should also be stopped for elective surgical procedures which involve fasting including day case procedures, or in patients fasting for religious reasons.
The risk of diabetic ketoacidosis (DKA) is elevated, including euglycaemic DKA. There is a mechanistic association with glycosuria and ketogenesis and this can be exacerbated during periods of physiological stress. The risk of this complication is small, particularly if good sick day guidance is provided.
SGLT2i should be avoided in type 1 diabetes, and where there is diagnostic doubt regarding the ‘type’ of diabetes, due to enhanced risk of DKA.
There should be caution where:
- People who have rapidly progressed to requiring insulin (within one year of diagnosis)
- Past history of DKA
- History of pancreatic disease – including alcoholic pancreatitis as a cause of their diabetes
- Testing of C-peptide can helpful although this requires interpretation, but caution should be
advised in people with very low levels of this peptide.
In people on significant diuretic doses (furosemide >40mg) consider reducing the dose as the SGLT2i will induce diuresis.
Urinary tract infection
SGLT2i are associated with an increased risk of fungal UTI in women, and serious genitourinary infection in men. These agents should be used in caution in patients with a relevant history. Vigilance regarding personal hygiene should be encouraged.
Give advice on the need to seek medical attention (via GP, pharmacy or urgent care centre) should they develop symptoms of a genital infection.
Peripheral vascular disease
In the CANVAS programme, there was an increased incidence of amputation in patients receiving canagliflozin, although this was not replicated in the CREDENCE study. A warning remains in the medicines compendium: “Before initiating Invokana, consider factors in the patient history that may increase the risk for amputation. As precautionary measures, consideration should be given to carefully monitoring patients with a higher risk for amputation events and counselling patients about the importance of routine preventative foot care and maintaining adequate hydration. Consideration may also be given to stopping treatment with Invokana in patients who develop events which may precede amputation such as lower-extremity skin ulcer, infection, osteomyelitis or gangrene”.