SGLT2 Inhibitors and GLP-1 Receptor Agonists

- January 3, 2024

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) e.g. empagliflozin & glucagon-like peptide-1 receptor agonists (GLP1RA) e.g. dulaglutide & liraglutide are increasingly being used in NZ for type 2 diabetes and other conditions such as heart failure & obesity. Currently their funded use is limited to type 2 diabetes under special authority criteria.


Mechanisms of action

  • SGLT2i inhibit glucose reabsorption in the renal proximal tubules & increase urinary glucose excretion.
  • GLP1RA increase glucose-dependent insulin secretion, reduce glucagon secretion & slow gastric emptying. They also reduce appetite & increase satiety.

Place in therapy

  • Lifestyle management & metformin remain first-line treatment for type 2 diabetes.
  • SGLT2i and GLP1RA are now the preferred second-line treatments, as their benefit in reducing cardiovascular risk is greater than other diabetes medicines. Regardless of glycaemic control, all patients with type 2 diabetes with a life expectancy more than a year will benefit from metformin & SGLT2i or GLP1RA.
  • SGLT2i improve outcomes for patients with heart failure or chronic kidney disease (even in those without diabetes), & are therefore recommended for patients with these co-morbidities.
  • GLP1RA likely lead to greater weight loss than SGLT2i, & are recommended if obesity predominates.
  • Both classes can be used together, but the current funding restrictions mean only one will be subsidised.
  • Empagliflozin is also approved in for heart failure, but is not funded for patients without diabetes.
  • Patients who aren’t eligible for funding, or who will benefit from use of both classes, can choose to self-fund.
  • Dipeptidyl peptidase-4 inhibitors (e.g. vildagliptin) increase endogenous GLP1 & are fully funded. Although less effective than GLP1RA, they can be combined with metformin & SGLT2i in most cases.
  • Liraglutide is approved but not funded for weight management in obesity. Dulaglutide is not approved or funded for weight loss but is sometimes used.

Practice Points

  • SGLT2i & GLP1RA do not themselves cause hypoglycaemia. Significant hypoglycaemia only occurs in patients taking insulin &/or sulfonylureas.
  • GLP1RA have a slightly greater glucose-lowering effect than the other non-insulin treatments.



• 10 mg/day orally

• increase to 25 mg/day if necessary

Renal impairment • efficacy decreases with worsening renal function

• avoid if eGFR <20 mL/min/1.73m2

Other medicines • concomitant insulin or sulfonylureas may need to be reduced
Adverse effects polyuria, genitourinary infections

• diabetic ketoacidosis:

• rare but can occur at normal or slightly raised blood glucose.

• interpret blood glucose with caution as patients can be severely insulin-deficient without high glucose.

• acute illness, procedures or excess alcohol increase risk.

• treat with IV glucose, insulin infusion & potassium.

Fournier’s gangrene:

• rare but has high mortality.

• perineal care & early recognition   & treatment reduce risk.


1.5 mg/week subcutaneously

higher doses sometimes used but additional effect is modest

Renal impairment
avoid if eGFR <15 mL/min/1.73m2
Other medicines
stop vildagliptin

concomitant insulin or sulfonylureas may need to be reduced

Adverse effects
gastrointestinal symptoms (common but usually transient)

pancreatitis, bowel obstruction (rare)

Sick-day & peri-procedural management

  • Acute illness: withhold SGLT2i & check blood ketones.
  • Minor day-stay procedures including bowel prep: stop SGLT2i the day before & day of surgery.
  • All other procedures: stop SGLT2i 2 days before & the day of surgery.
  • Restart SGLT2i when eating & drinking normally.
  • GLP1RA can be continued.
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