SGLT2 inhibitors

Patients can now be started on funded liraglutide (Victoza) and there is dual funding of empagliflozin (Jardiance) and GLP1Ra for people with type 2 diabetes and heart failure – please click here for more information.

SGLT2 inhibitors are preferred 2nd line agents in cardiovascular disease, especially heart failure, and renal disease as these reduce mortality from cardiovascular events and renal disease progression independent of effects on glycaemic control; and lead to weight loss, blood pressure reduction and will not cause hypoglycaemia in or of itself. SGLT2 inhibitors are also preferred options for people with heart failure (with or without type 2 diabetes) and can be funded for this indication specifically (allowing dual funding of SGLT2i and GLP1RA for type 2 diabetes).Therefore, SGLT2 inhibitors (SGLT2i) should be strongly considered in all patients with type 2 diabetes with diabetic renal disease (urinary albumin:creatinine ratio > 3 mg/mmol and/or reduced eGFR) OR heart failure.

Effective from 1^st September 2026, the Special Authority criteria do not require any comorbidity or presence of any level of cardiorenal risk in applying for the special authority (see SA form ), and all existing Special authorities remain active. Note that SGLT2 inhibitors have diminishing HbA1c lowering impact in those with lower eGFR, and a GLP1RA would be more appropriate for glucose lowering, weight loss and cardiorenal benefits. Nevertheless, funding of both an SGLT2 inhitor and a GLP1RA is still prevented at this time except for the group with co-existing CHF (CHF SGLT2 Inhibitor ). This is at odds with Best Practice and clinical need in the highest risk groups.
To date, there is no convincing evidence that SGLT2i are effective in primary prevention of cardiovascular and/or renal disease. But, in patients

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

Special Authority Criteria for Subsidy

Initial application — (Type 2 Diabetes) from any relevant practitioner. Approvals valid without further renewal unless notified for applications meeting the following criteria:
Both
Patient has type 2 diabetes; and
Target HbA1c (of 53 mmol/mol or less) has not been achieved despite the regular use of at least one blood-glucose lowering agent (e.g. metformin, vildagliptin, or insulin) for at least 3 months; OR
Patient has previously had an initial approval for a GLP-1 agonist and is changing funded treatment to an SGLT2i; AND
Funded empagliflozin or empagliflozin with metformin hydrochloride is not to be prescribed in combination with a funded GLP-1 agonist unless for the treatment of heart failure.

SGLT2 inhibitors 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

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 can increase to maximum of 25 mg daily after several weeks if no adverse effects AND as required for glycaemic control. NB: The glucose lowering efficacy of SGLT2i is reduced with decreasing renal function and the maximum dose of empagliflozin is 10 mg daily once the eGFR is < 30 mL/min

Non-funded SGLT2i available in New Zealand includes dapagliflozin 10 mg po daily

The mutually exclusive funding/special authority criteria for SGLT2i and GLP1RA ( except in heart failure) in New Zealand is not fully consistent with Best Practice. Although expensive at approximately $85 per month, all patients with type 2 diabetes who would benefit from treatment with a SGLT2 inhibitor but are already funded for a GLP1RA ( the more expensive of the two classes) should be counselled as to the benefits of adding the SGLT2 inhibitor, and let them decide if they can afford the cost.

Even though the new special authority criteria no longer require the presence and explicit mention of high risk factors/comorbidities (e.g. established or high risk IHD, renal impairment or CHF) optimised management of these risk factors/comorbidities is still paramount and follows usual guidelines .

When choosing between SGLT2i and GLP1RA
- CVD risk reduction: GLP1RA offer stronger protection
- Heart failure: SGLT2i are superior
- Higher BMI – GLP1RA are better although if can self-fund Wegovy or Tirzepatide, these are more effective for weight loss and glycaemic control than funded dulaglutide or liraglutide, especially if MASH (semaglutide) or OSA (Tirzepatide).
- Renal function – while still renoprotective independent of eGFR, glucose lowering efficacy relies on renal function and glucose lowering diminishes with reduced eGFR.
- Higher baseline HbA1c - GLP1RA generally provides greater HbA1c reduction than SLGT2i
  - Funded dulaglutide 1.5mg weekly, and liraglutide 1.8mg daily are essentially equivalent in glucose lowering efficacy and provide roughly twice the HbA1c reduction than achieved by empagliflozin 25mg od
  - Unfunded GLP1RA- semaglutide and tirzepatide provide greater HbA1c reduction and greater BMI reductions than dulaglutide or liraglutide or empagliflozin (see GLP1RA section)

When starting SGLT2i:
- Provide ongoing support and education for lifestyle management
- Metformin should be continued unless contraindicated or not tolerated
- Other glucose lowering therapies should be continued if required for glycaemic control and/or cardiorenal protection (e.g. GLP1RA)
- 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). Any reduction is best based on blood glucose levels, but recommended proactive reductions in those with tight glycaemic control include a:
  - 15-20% reduction in the dose of total daily insulin. Consider switching premixed insulin or basal plus one insulin regimens to insulin alone if HbA1C < 64 mmol/mol.
  - 50% reduction in the doses of sulfonylureas. Consider stopping sulfonylureas for those on ≤ 80 mg of glicazide per day or ≤ 5 mg of glipizide per day if HbA1c < 64 mmol/mol.
  - NB: Patients with an HbA1c > 75 mmol/mol with no episodes of hypoglycaemia will typically not require any reduction in insulin and/or sulfonylureas
- Warn of the potential adverse effects and reassure that mild symptoms typically resolve despite continuing treatment. Consider reducing diuretics and antihypertensives if required and discuss importance of remaining well hydrated and sick day management plan (see adverse effects below).

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 normoglycaemic DKA but still 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 at least 3 days (including day of) before any major elective procedure or any elective procedure that involves reduced oral intake for > 12 hours (including dental surgery). Also need to stop SGLT2i at least 3 days before any bowel prep (e.g. colonoscopy) or a low carbohydrate diet (e.g. bariatric surgery) pre-procedure. The SGLT2i should not be restarted until the patient is well and eating and drinking normally as per their sick day management plan. For more information please see NZSSD/ADS alert
Patients should informed to present to their GP practice or hospital if experiencing symptoms of nausea, vomiting or abdominal pain to have their ketones checked
Capillary ketones > 1.5 mmol/L on SGLT2i 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 (e.g < 130 g of carbohydrate per day) and/or significant alcohol use

SGLT2i are not recommended for use in:

Children < 10 years, pregnancy and breastfeeding
eGFR < 20 mL/min*
- *NB: International guidelines (e.g. KDIGO) now recommend that all SGLT2i including empagliflozin can be started safely when the eGFR is > 20 mL/min and only need to be stopped if adverse effects occur of if the patient starts dialysis.
Previous severe genitourinary infections
Those on ketogenic diets (due to increased risk of DKA )
Type 1 diabetes, diabetes due to loss of pancreatic function, or previous DKA without specialist approval

Risk factors for DKA in type 2 diabetes

Previous DKA
Insulin deficiency with low carbohydrate diet (e.g < 130 g of carbohydrate per day) and/or significant alcohol use

Type 2 Diabetes Management Guidelines

More reading...

References: