TABLE 4.

Considerations for Management of Ketosis/DKA

	STICH (20)	International Consensus (18)	STOP DKA (19)	Anne L. Peters’ Protocol (14)	EMA Guidance (11,12)	NICE Guidance (21–23)
Stages of ketonemia/DKA by ketone level (BHB), mmol/L, or ketonuria	• >3.0 or significant ketonuria (more than ++): DKA	• 0.6–1.5 or trace/small/+ urine reading: ketonemia	• <1.0: normal or mild	• 0.6 mmol/L: ketonemia	• 0.6–1.5 or trace/small/+ urine reading: ketonemia	NA
		• 1.6–3.0 or moderate/++ urine reading: impending DKA	• 1.0–1.4: moderate		• >1.5–3.0 or moderate/++ urine reading: impending DKA
		• >3.0 or large/very large/+++/++++: probable DKA	• 1.5–2.9: high		• >3.0 or large/very large/+++/++++ urine reading: probable DKA
			• ≥3: extreme
Other measures of DKA	• Blood glucose >200 mg/dL	NA	NA	NA	NA	NA
	• Bicarbonate <15.0 mmol/L
	• Venous pH <7.3
Stopping SGLT2i	When high ketones are detected, stop SGLT2i for a few days	When elevated ketones are present, discontinue SGLT2i until ketones are back to baseline	Stop SGLT2i when DKA symptoms (lethargy, loss of appetite, nausea, abdominal pain) are present	If any signs/symptoms of physical illness occur, stop SGLT2i and test ketones	• Stop SGLT2i if BHB >1.5 mmol/L or at moderate/++ urine ketone reading	• Assess A1C after 6 months and regularly thereafter; if no sustained improvement in glycemic control (>0.3% drop in A1C), stop dapagliflozin
					• Stop SGLT2i if ketone levels persist and symptoms are still present with ketonemia	• Stop at eGFR consistently <40 mL/min/1.73 m2
Carbohydrate and fluid intake	• 30–60 g carbohydrates	• Ketonemia: 15–30 g carbohydrates; 300–500 mL fluids hourly	• 30–60 g carbohydrates	• If ketones >0.6 mmol/L, increase carbohydrate intake, give more insulin, drink fluids, and hold SGLT2i until back to baseline	• Patient may need to drink water	NA
	• 200–500 mL fluids hourly	• Impending DKA: same as above; also consider seeking medical attention	• 200–500 mL fluids hourly	• Monitor until ketones return to normal	• Extra carbohydrates should be taken if blood glucose is normal or low
		• Probable DKA: seek immediate medical attention	• Also depends on blood glucose
Correction insulin	1.5 times the usual dose	Based on carbohydrate intake	• Moderate or higher ketones: consider increasing basal insulin by 20–50% until return to baseline	See description in text; give carbohydrates + correction dose; 1.5 times the usual correction dose if >200 mg/dL	Need to take extra rapid-acting insulin	NA
			• Calculate specific correction bolus insulin based on blood glucose and ketone level or use daily dosage calculation based on Table 6B in the STOP DKA report (19)
Frequency of additional correction insulin and carbohydrates	Every 1–2 hours	Every hour	Every 2–4 hours	Every 1–2 hours	NA	NA
Frequency of ketone checks during ketosis/DKA	Every 2–4 hours	If BHB >0.6 mmol/L, every 3–4 hours until resolution	Every 2–4 hours	Every 1–2 hours	2 hours after initial check	NA
Frequency of glucose checks during ketosis/DKA	NA	Frequently	Every 2–4 hours	Every 1–2 hours with ingestion of carbohydrates and fluids	Check glucose levels frequently to avoid hyperglycemia or hypoglycemia	NA
When to seek medical attention	• Ketone levels >3.0 mmol/L, any management steps cannot be followed, or ketonemia does not resolve in 4–6 hours	• At “probable DKA” BHB or urine reading	• If high levels of ketones persist despite extra insulin and/or increased carbohydrate intake over a period of 6–10 hours	• If unable to keep down fluids, go to emergency department; otherwise, contact HCP if ketones are increasing and not responding to treatment within 1–2 hours	>3.0 or large/very large/+++/++++ urine reading	NA
	• If there are symptoms of	• If DKA symptoms and/or ketones are worsening	• If vomiting	• Always contact HCP if in doubt
	DKA, including abdominal pain, nausea, vomiting, fatigue, and/or dyspnea		• If unable to keep down fluids
			• If there are persistent symptoms of DKA

SGLT2i, SGLT2 inhibitor.