Published: 2 September 2021

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Empagliflozin: advise patients on the risk of ketoacidosis and Fournier’s gangrene

Published: 2 September 2021
Prescriber Update 42(3): 38–40
September 2021

Sodium glucose co-transporter 2 (SGLT2) inhibitors, such as empagliflozin, are used in the treatment of type 2 diabetes mellitus to improve glycaemic control and reduce the risk of cardiovascular events in adults.

These medicines have been associated with the serious and sometimes life-threatening conditions of diabetic ketoacidosis (DKA) and Fournier’s gangrene (necrotising fasciitis of the perineum).¹ Cases of DKA and Fournier’s gangrene have been reported to the Centre for Adverse Reactions Monitoring (CARM) following initiation of empagliflozin.

Diabetic ketoacidosis

The signs and symptoms of DKA are described in Table 1. Patients taking SGLT2 inhibitors are at increased risk of DKA, particularly within the first few months of treatment or peri-operatively.^2,3 In some cases, DKA can be atypical with near normal or only slightly raised blood glucose levels (euglycaemic diabetic ketoacidosis).²

Risk factors for DKA in patients being treated with empagliflozin include:^1,4

• insulin dose reduction
• a low carbohydrate diet
• alcohol abuse
• severe dehydration
• pancreatic disorders, such as a history of pancreatitis or pancreatic surgery
• metabolically stressful events, such as severe infection, myocardial infarction, stroke, surgery, prolonged fasting.

Consider stopping empagliflozin temporarily during an acute illness, particularly if patients are unwell, febrile and not eating or vomiting. Empagliflozin should also be temporarily stopped before undergoing medical procedures or surgery^3,5 – consult local clincal guidelines for advice.

Advise patients to seek medical attention if they experience signs and symptoms of DKA (Table 1).

Table 1: Signs and symptoms of diabetic ketoacidosis (DKA) and what to do

Signs and symptoms

What to do

Can include: difficulty breathing nausea vomiting anorexia excessive thirst abdominal pain confusion and unusual fatigue or sleepiness a sweet smell to the breath a sweet or metallic taste in the mouth a different odour to urine or sweat. More serious signs and symptoms include: dehydration deep gasping breathing confusion coma.

Patient Seek medical attention if experiencing the signs and symptoms of DKA, regardless of the blood glucose level. Health care professional Test blood capillary ketones (urine ketone testing may be unreliable). Suspect DKA in patients with or without hyperglycaemia, who are experiencing symptoms of DKA: and/or a finger prick capillary blood ketone level is above 1.00 mmol/L and/or a negative base excess of below -5 mmol/L, indicating metabolic acidosis. Stop empagliflozin and treat the DKA.

Source: New Zealand Formulary (NZF). 2021. NZF v108: Empagliflozin 1 June 2021. URL: nzf.org.nz/nzf_71055 (accessed 25 June 2021).

Fournier’s gangrene (necrotising fasciitis of the perineum)

Fournier’s gangrene is a necrotising bacterial infection of the perineum. It has been reported in both female and male patients on empagliflozin. Serious outcomes have included hospitalisation, multiple surgeries and death.^1,6

Advise patients to seek immediate medical attention if they experience pain, tenderness, redness or swelling of the genital or perineal area, particularly with associated fever or malaise. These symptoms can worsen quickly.⁶

Initiate treatment promptly with a broad-spectrum antibiotic and surgical debridement, if necessary.⁶

Discontinue empagliflozin and provide an alternative therapy for glycaemic control.⁶

New Zealand case reports

Up to 30 June 2021, CARM has received:

• three reports of DKA, one of which was reported to be euglycaemic (CARM IDs: 139444, 140085, 140811)
• two reports of Fournier’s gangrene (CARM IDs: 140656, 140811).

Empagliflozin was listed as the suspect medicine in all of these reports.

More information

See the following Prescriber Update articles for more information:

• Spotlight on empagliflozin (December 2020):
• SGLT2 Inhibitors and diabetic ketoacidosis (December 2015).

References

1. Boehringer Ingelheim (NZ) Limited. 2019. Jardiance New Zealand Data Sheet 4 December 2019. URL: medsafe.govt.nz/profs/datasheet/j/jardiancetab.pdf (accessed 25 June 2021).
2. New Zealand Forumulary (NZF). 2021. NZF v108: Empagliflozin 1 June 2021. URL: nzf.org.nz/nzf_71055 (accessed 25 June 2021).
3. bpac^nz. 2021. New diabetes medicines funded: empagliflozin and dulaglutide March 2021. URL: bpac.org.nz/2021/diabetes.aspx (accessed 25 June 2021).
4. Access Lexicomp Online. 2021. Empagliflozin: Drug information. In: UpToDate v176.0. URL: uptodate.com/contents/empagliflozin-drug-information (accessed 6 July 2021).
5. New Zealand Society for the Study of Diabetes. 2020. Periprocedural diabetic Ketoacidosis (DKA) with SGLT2 inhibitor use January 2020. URL: diabetessociety.com.au/documents/ADS_DKA_SGLT2i_Alert_update_2020.pdf (accessed 16 July 2021).
6. US Food and Drug Administration. 2018. FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes29 August 2018. URL: fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-occurrences-serious-infection-genital-area-sglt2-inhibitors-diabetes (accessed 25 June 2021).