Can an otherwise healthy adult with type 2 diabetes, eGFR ≥ 60 mL/min/1.73 m², no history of recurrent ketoacidosis, and not pregnant or breastfeeding safely use a ketogenic diet together with a sodium‑glucose co‑transporter‑2 inhibitor for glycaemic control?

Ketogenic Diet Plus SGLT2 Inhibitor for Type 2 Diabetes: Safety Assessment

This combination should NOT be used together due to the substantial risk of euglycemic diabetic ketoacidosis (euDKA), a potentially life-threatening complication that can occur even with normal blood glucose levels. 1, 2, 3

Why This Combination Is Dangerous

The 2025 ADA Standards of Care explicitly warn that very-low-carbohydrate eating plans (including ketogenic diets) should be used with caution in patients taking SGLT2 inhibitors because of the potential risk of ketoacidosis. 1

• Multiple case reports document euDKA occurring in patients combining SGLT2 inhibitors with ketogenic diets, with onset as rapid as after a single dose of empagliflozin or within one week of starting the ketogenic diet. 2
• The mechanism involves SGLT2 inhibitors promoting ketogenesis through glucosuria and reduced insulin secretion, while the ketogenic diet simultaneously increases ketone body production—creating a synergistic effect that can trigger ketoacidosis even at normal glucose levels (euDKA). 4
• Diabetologia's 2022 umbrella review specifically identifies metabolic ketoacidosis with ketogenic diets as a hazard, particularly with SGLT2 inhibitors. 1

Clinical Presentation of euDKA

• Patients present with nausea, vomiting, dyspnea, generalized weakness, and sweating—but without marked hyperglycemia, making diagnosis challenging in emergency settings. 3
• Blood glucose may be normal or only mildly elevated (e.g., 181 mg/dL), with elevated anion gap and ketonuria on urinalysis. 2, 3
• The absence of significant hyperglycemia frequently delays diagnosis, as clinicians may not suspect DKA when glucose is near-normal. 3

Evidence-Based Alternative Approaches

For Glycemic Control Without Cardiovascular/Renal Disease

Start metformin plus lifestyle modifications, then add an SGLT2 inhibitor OR GLP-1 receptor agonist (such as tirzepatide) when glycemic targets are not met—but never combine SGLT2 inhibitors with a ketogenic diet. 1, 5

• If the patient prioritizes substantial weight loss, choose a GLP-1 receptor agonist over an SGLT2 inhibitor, as GLP-1 RAs provide superior weight reduction without the ketoacidosis risk when combined with carbohydrate restriction. 5
• If the patient has heart failure or chronic kidney disease, prioritize the SGLT2 inhibitor for proven cardiorenal protection—but counsel the patient to maintain adequate carbohydrate intake (minimum 130 grams daily) to prevent ketosis. 1, 5

For Patients Desiring Carbohydrate Restriction

If the patient insists on following a very-low-carbohydrate or ketogenic diet for diabetes management, discontinue the SGLT2 inhibitor and use metformin plus a GLP-1 receptor agonist instead. 1, 5

• The 2025 ADA Standards recommend maintaining consistent medical oversight of individuals following very-low-carbohydrate eating plans, with recognition that insulin and other diabetes medications may need adjustment to prevent hypoglycemia. 1
• Very-low-carbohydrate diets can reduce HbA1c by approximately 2% in the short term (<6 months), with less difference in long-term effects, making them effective for glycemic control when properly supervised. 1
• GLP-1 receptor agonists do not increase ketone production and therefore do not synergize with dietary ketosis to cause ketoacidosis. 5

Monitoring Requirements If Patient Refuses to Discontinue Either Intervention

If the patient refuses to stop either the SGLT2 inhibitor or the ketogenic diet despite counseling, implement intensive monitoring with explicit written instructions to discontinue the SGLT2 inhibitor immediately if any symptoms of ketoacidosis develop. 1, 2

• Provide written instructions listing symptoms: nausea, vomiting, abdominal pain, dyspnea, confusion, or unusual fatigue. 2, 3
• Instruct the patient to check urine ketones daily using over-the-counter ketone strips and to seek emergency care if moderate-to-large ketones are present with any symptoms. 2
• Schedule follow-up within 2 weeks of starting this combination, then monthly for the first 3 months. 1
• Document the patient's refusal to follow medical advice and the specific risks discussed in the medical record. 1

Additional Safety Considerations

• Avoid excessive alcohol intake when taking SGLT2 inhibitors, as alcohol further increases ketoacidosis risk. 1
• Temporarily discontinue the SGLT2 inhibitor during acute illness, surgery, prolonged fasting, or any situation that might precipitate ketosis. 1, 4
• The 2022 Diabetologia review notes that ketogenic diets can cause thiamine deficiency leading to heart failure and neurological problems, as well as reduced intakes of folate, iron, and magnesium—risks that compound the cardiovascular concerns in diabetes patients. 1

What the Evidence Shows About Ketogenic Diets Alone

• A 2023 systematic review found that ketogenic diets consistently demonstrate improved glycemic control in type 2 diabetes, but noted that studies lack exploration of long-term effects on the liver, with one study showing that while a ketogenic diet improved glycemic control, it created problems with lipid metabolism and hepatic steatosis. 6
• When pairing a ketogenic diet with exercise, hepatic steatosis was avoided in the single study that examined this outcome. 6
• The evidence for ketogenic diets in diabetes is limited by short follow-up duration and lack of safety data on long-term metabolic effects. 1, 6