What precautions should be taken with Sodium-Glucose Linked Transporter (SGLT) inhibitors, such as empagliflozin (Jardiance), dapagliflozin (Farxiga), and canagliflozin (Invokana), in patients experiencing vomiting and diarrhea?

SGLT Inhibitors in Vomiting and Diarrhoea

SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) must be temporarily stopped immediately when patients develop vomiting or diarrhea to prevent life-threatening ketoacidosis and volume depletion. 1

Immediate Action Required

Temporarily discontinue SGLT2 inhibitors when any of the following occur: 1

• Vomiting or diarrhea resulting in significant fluid losses
• Inability to maintain normal oral fluid intake
• More than 4 episodes of vomiting in 12 hours
• Any acute illness with reduced food/fluid intake 1, 2

The 2023 American Journal of Kidney Diseases consensus guidelines achieved 96% expert agreement (22/23 votes) that SGLT2 inhibitors should be held during acute illness with volume depletion 1. This recommendation is reinforced by the 2025 KDOQI guidelines, which explicitly list holding SGLT2 inhibitors during nausea, vomiting, and diarrhea as a key mitigating strategy 1.

Critical Risks During Acute Illness

The combination of SGLT2 inhibitors with vomiting/diarrhea creates three life-threatening risks: 1, 3

• Euglycemic diabetic ketoacidosis (DKA): Can occur even with normal blood glucose levels (<250 mg/dL), requiring immediate recognition and treatment 1, 2, 3
• Severe volume depletion: SGLT2 inhibitors promote natriuresis, glycosuria, and free water loss, which compounds fluid losses from vomiting/diarrhea 4, 5
• Acute kidney injury: Sudden kidney injury has been documented in patients taking SGLT2 inhibitors during volume depletion 1, 3

A 2023 case report documented life-threatening acidosis (pH <6.7, bicarbonate <5 mmol/L) in a patient on dapagliflozin and metformin who developed vomiting and diarrhea, requiring intubation, vasopressors, and dialysis 4. This underscores the severity of continuing SGLT2 inhibitors during gastrointestinal illness.

Duration of Withholding

Hold SGLT2 inhibitors for up to 72 hours or until symptoms resolve, whichever comes first: 1

• Stop medication immediately when symptoms begin
• Continue withholding until normal eating and drinking resume 2, 6
• For planned procedures, withhold for 3-4 days before surgery (canagliflozin, dapagliflozin, empagliflozin ≥3 days; ertugliflozin ≥4 days) 1, 2

The FDA-approved labeling for empagliflozin (Jardiance) specifically warns that "when your body is under some types of stress, such as fever, trauma, infection, or surgery, the amount of diabetes medicine that you need may change" and instructs patients to contact their doctor immediately under these conditions 3.

Monitoring Requirements During Illness

Patients must be monitored for ketoacidosis even with normal glucose levels: 1, 2

• Check blood or urine ketones if patients develop malaise, nausea, or vomiting 2
• Monitor for moderate or high ketones, which should prompt immediate healthcare provider contact (91% consensus agreement) 1
• Assess volume status carefully, as dehydration risk is significantly elevated 1, 2

The 2018 ADA/EASD consensus report notes that SGLT2 inhibitors "should be used with caution and appropriate patient education should be provided" and that "caution should be taken when SGLT2 inhibitors are used in combination with diuretics" 1.

Special Considerations for Insulin Users

For patients on insulin, maintain at least low-dose insulin even when SGLT2 inhibitors are held: 1, 2

• Complete insulin cessation increases DKA risk dramatically 1, 2
• Do not reduce insulin doses excessively when holding SGLT2 inhibitors during illness 2
• Dose adjustment of insulin may be needed, but complete discontinuation should be avoided 1

When to Resume SGLT2 Inhibitors

Resume SGLT2 inhibitors only after all of the following are met: 1, 2

• Acute illness symptoms have completely resolved
• Normal oral intake of food and fluids is re-established 2
• Patient has been eating and drinking normally for 24-48 hours 1
• Volume status has normalized

The consensus guidelines achieved 100% agreement (25/25 votes) that patients should seek healthcare provider assistance when symptoms last more than 72 hours 1.

Patient Education Essentials

Counsel patients to stop SGLT2 inhibitors immediately and contact their healthcare provider when: 1, 2

• They develop vomiting, diarrhea, or reduced ability to eat/drink normally
• They experience nausea, abdominal pain, tiredness, or trouble breathing (potential DKA symptoms) 3
• They become sick with any acute illness requiring reduced food/fluid intake 2

The 2025 KDOQI guidelines emphasize implementing a "sick day protocol" and educating patients on early recognition of complications as essential mitigating strategies 1.

Common Pitfall to Avoid

Do not continue SGLT2 inhibitors "because blood sugar is well-controlled." Euglycemic DKA is a unique and dangerous complication where ketoacidosis develops despite normal or near-normal glucose levels 1, 2, 3. The FDA labeling for empagliflozin explicitly warns that "ketoacidosis can happen with JARDIANCE even if your blood sugar is less than 250 mg/dL" 3.