Drug Summary - SGLT2 Inhibitors

(Refer to: Drug review - SGLT2 Inhibitors for review and references)

MOA	By inhibiting SGLT2, gliflozins reduce renal glucose reabsorption, leading to increased urinary excretion of excess glucose and a reduction in plasma glucose concentrations in a non-insulin dependent manner
Glycaemic efficacy and indications	As monotherapy: 0.6% to -1.2%; non-inferior to metformin As add on to metformin: -0.5% to -1.0%; non-inferior to other classes As add on to metformin + SU: -0.7% to -0.9%; non-inferior to DPP-4 inhibitors As add on to insulin therapy: -0.5% to -0.8%
Microvascular Outcomes	No primary outcome studies
Macrovascular and Mortality Outcomes	Empagliflozin therapy was associated with a reduction in all-cause death, cardiovascular-death and hospitalisation for heart failure in patients with established cardiovascular disease. There has been no signal of adverse cardiovascular outcomes in systematic meta-analyses for the other SGLT2 inhibitors
Hypoglycaemia	Hypoglycaemia rates are not different to placebo except when SGLT2 inhibitors are combined with insulin or insulin secretagogues
Non-glycaemic benefits	Mean weight loss of 1.6 to 2.5 kg; not different to GLP-1RAs (meta-analysis) Systolic and diastolic blood pressure reduction (-4.0 and -1.5 mmHg) respectively
Side effects and precautions	Mycotic genital infections are common (and more so in women); do not use in patients with a history of recurrent genital infections The risk of urinary tract infections may be increased but can be minimised by advising adequate hydration and fastidious bathroom hygiene; do not prescribe SGLT2 inhibitors in patients with a history of recurrent UTI Dehydration and hypotension can occur particularly in susceptible patients (treated with loop diuretics, have advanced cardiac disease or older than 65 years). Always ensure and emphasise adequate hydration when prescribing SGLT2 inhibitors eGFR usually declines within the first weeks of initiating therapy and then gradually returns toward baseline. Monitor eGFR and discontinue SGLT2 inhibitors if the decline is ≥ 30% Diabetic ketoacidosis may occur at mildly elevated levels of blood glucose particularly in insulin treated patients Warn patients of the symptoms of DKA and advise them to seek medical attention immediately The risk of fractures and lower-limb (especially toe) amputations is increased with canagliflozin Therefore do not use canagliflozin, and exercise caution with the other drugs in this class, in patients who are at high risk for these conditions Do not prescribe dapagliflozin to patients with bladder cancer or in combination with pioglitazone
Dosing	eGFR	Dapagliflozin	Empagliflozin	Canagliflozin
	≥60 ml/min 45-60 ml/min 45-60 ml/min	5 mg or 10 mg Contraindicated Contraindicated	10 mg or 25 mg Continue 25 mg but do not initiate therapy Contraindicated	100 mg or 300 mg Continue 100 mg but do not initiate therapy Contraindicated
Cost	Unknown; not registered in South Africa as at March 2017

 

(See Strength of Recommendations Taxonomy (SORT) for explanation of Grade A-C)

SEMDSA 2017 Recommendations for SGLT2 inhibitors
Do not use SGLT2 inhibitors as initial monotherapy	C
Consider a SGLT2 inhibitor as add-on (dual therapy) to metformin (or other initial drug therapy) in selected patients not achieving or maintaining their glycaemic targets	A
Consider a SGLT2 inhibitor as the 3rd glucose lowering drug in selected patients not achieving or maintaining their glycaemic targets on an existing oral two-drug regimen	A
Circumstances where an SGLT2 inhibitor may be preferred to other treatment options: Overweight and obese patients Weight gain or hypoglycaemia has been, or is likely to be problematic with other treatment options Patients with established cardiovascular disease (empagliflozin benefit); to be managed at specialist care level
Circumstances where an SGLT2 inhibitor may not be the preferred option: Patients with recurrent mycotic genital infections or urinary tract infections Patients at risk for dehydration and hypotension Patients at high risk for stroke, fracture (canagliflozin), amputation (canagliflozin), bladder cancer (dapagliflozin) or ketoacidosis (refer to drug review)	C
Do not initiate SGLT2 inhibitors when the eGFR is < 60 ml/min/m2
Stop all SGLT2 inhibitors when the eGFR is < 45 ml/min/m2

 

Caution:

Do not persist with any chosen treatment if the HbA_1C has not decreased by > 0.5% after six months

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