SGLT2 inhibitors

Is a preferred 2nd line agent in cardiovascular disease, especially heart failure, and renal disease as reduces mortality cardiovascular events and renal disease progression independent of effects on glycaemic control; and leads to weight loss, blood pressure reduction and will not cause hypoglycaemia in or of itself

Reduce glucose levels and circulating volume by inhibiting the sodium glucose co-transporter 2 (SGLT2) in the proximal renal tubule leading to increased urinary excretion of glucose and sodium

All available SGLT2i in New Zealand are tablets

Empagliflozin is the only funded SGLT2i in NZ under special authority criteria

Special Authority Criteria

Patient has type 2 diabetes with diabetic renal disease (urinary albumin:creatinine ratio > 3 mg/mmol and/or eGFR < 60 mL/min), known cardiovascular disease or 5 year CVD risk > 15%
Type 2 diabetes with HbA1c > 53 mmol/mol despite maximal tolerated dose of metformin and/or alternative glucose lowering therapy for 6 months
The patient is not on a funded GLP1RA

Available in 10 mg and 25 mg tablets or in various empagliflozin/metformin combinations (5 mg/500 mg; 5 mg/1000 mg; 12.5 mg/500 mg; 12.5 mg/1000 mg)

Typically start at 10 mg daily and increase to maximum of 25 mg daily if no adverse effects and as required for glycaemic control

Non-funded SGLT2i available in New Zealand includes dapagliflozin 10 mg po daily (costs approximately $85 per month)

Adverse effects of SGLT2 inhibitors

Polyuria – consider reducing diuretics before commencing if applicable

Genitourinary infections e.g. UTIs, vaginal thrush, balantitis

Patients should be educated on correct hygiene and warned of the rare risk of Fournier’s gangrene that is a medical emergency

Fournier's gangrene is a type of necrotising fasciitis involving the external genitalia, perineal or perianal areas and may be life threatening. Although the vast majority of genitourinary infections associated with SGLT2 inhibitors are mild, consider acute referral to secondary care if significant pain, fevers and redness out of keeping with mild infection

Hypotension – consider reducing antihypertensive agents before commencing/increasing dose

Increases risk of diabetic ketoacidosis (DKA) including normoglycaemicstill rare (1 in 3000)

NB: Patients and health professionals need to be aware of the risk of DKA with SGLT2i (including with normal glucose levels)

Need to stop SGLT2i in acute illness or 2 days before an elective procedure (NZSSD/ADS alert )
Patients should informed to present to their GP practice or hospital if experiencing symptoms of nausea, vomiting to have their ketones
Capillary ketones > 1.5 mmol/L require urgent medical attention
Cautious use of SGLT2i in type 2 diabetes is recommended for those high risk for DKA

Risk factors for DKA in type 2 diabetes

Previous DKA
Insulin deficiency with low carbohydrate diet and/or significant alcohol use

Not recommended for people on ketogenic diets and type 1 diabetes

If introduced to a regimen with insulin and/or sulfonylureas, then the dose of insulin and/or sulfonylureas may need to be reduced to prevent hypoglycaemia (particularly if the HbA1c is < 64 mmol/mol)

Not registered for use:

eGFR < 30 mL/min
Type 1 diabetes, diabetes due to loss of pancreatic function, or previous DKA without specialist approval

Not recommended for use in:

Children or youth (< 18 years), pregnancy and breastfeeding
Previous severe genitourinary infections
Nephrolithiasis/recurrent renal calculi

Need to stop with any intercurrent illness or 2 days before an elective procedure as per sick day management plan

Type 2 Diabetes Management Guidelines

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