Introduction

Scope: adults only. Pediatric DKA carries cerebral-edema risk and follows separate protocols. This pearl teaches the SQuID approach and its safety rules; it is not a standalone order set — use your institution's validated SQuID order set (with its full dextrose-titration and hypoglycemia branches) to write orders.

Case Presentation

  • A 24-year-old adult with type 1 diabetes presents after two days of vomiting and missed insulin.
    • Glucose 480 mg/dL, beta-hydroxybutyrate 4.2 mmol/L, venous pH 7.25, bicarbonate 15 mmol/L, anion gap 22, potassium 4.4 mEq/L.
    • She is alert and hemodynamically stable. This is mild-to-moderate DKA.
  • Does she need an ICU bed and an insulin drip?
    • Increasingly, no — if she can be monitored closely, subcutaneous insulin (the SQuID pathway) is a recognized alternative.

Clinical Detail

Pharmacology — Insulin in the SQuID Pathway

SC dose = per dose, NOT per hour. Illustrative of the SQuID approach; write orders from the validated institutional order set.

ParameterDetail
SC rapid-acting (SQuID, mild-moderate)
  • Rapid-acting analogue (lispro; aspart in some protocols): about 0.2 units/kg SC per dose while glucose is above 250 mg/dL
  • Step down to about 0.1 units/kg SC per dose once glucose is 250 mg/dL or below and dextrose is running; repeat about every 2 hours (the SQuID interval; ADA permits q1–2h)
  • Hold or reduce for hypoglycemia per the order set. Dose by the institution-approved dosing weight; no validated fixed cap exists — in very high body weight follow the institutional dosing-weight rule or obtain endocrine/pharmacy review
⚠ Hold rule (potassium)
  • Do NOT give insulin until serum K > 3.5 mmol/L. Insulin drives potassium intracellularly and can precipitate lethal hypokalemia. Replace potassium first and re-check before dosing
Dextrose
  • Start dextrose (D5 in the IV fluid) once glucose is 250 mg/dL or below, so insulin keeps clearing ketones without causing hypoglycemia; titrate dextrose to hold glucose in a safe range while correction dosing continues
  • This is fluid-delivered dextrose in the SC pathway, not a fixed-rate-drip “two-bag” system
Basal insulin (conditional)
  • If the patient is already on home basal insulin, continue it and do NOT stack a second weight-based basal dose
  • If starting basal, ADA 2026 supports glargine 0.15–0.3 units/kg. (Thammakosol RCT tested glargine 0.3 u/kg added to an IV infusion, single-center, open-label, N=60, mostly type 2 DM; extended to the SC pathway by analogy)
IV regular insulin (contrast case, severe DKA)
  • For severe DKA on a drip: fixed-rate 0.1 units/kg/hr, no bolus. An initial 0.1 u/kg IV bolus is reserved for an anticipated delay in establishing the infusion, not a routine alternative
  • Shown only as the pathway SQuID replaces for mild-moderate patients
Euglycemic / SGLT2i DKA
  • Not a SC/SQuID candidate. SGLT2-inhibitor-associated (euglycemic) DKA may present with glucose below 200 mg/dL and prolonged ketogenesis, which breaks the glucose-triggered SC dosing logic. Treat as complicated: IV insulin plus early dextrose, close monitoring
Monitoring
  • POC glucose q1–2h; potassium at baseline, 2 h after insulin starts, then every 4 h while correction insulin is active; BHB and venous pH q4h until resolution
  • Track BHB (not urine ketones) for resolution
Escalate to IV infusion if
  • Ketosis/acidosis is not improving, the anion gap is not narrowing, glucose is static despite dosing, the patient decompensates, or q2h monitoring cannot be maintained. Do not persist on the SC pathway when it is failing

Keys to the SQuID Pathway (2024 ADA Consensus)

ParameterDetail
Diagnosis (ADA 2024)
  • Glucose ≥200 mg/dL (or known diabetes) + beta-hydroxybutyrate ≥3.0 mmol/L (or urine ketones ≥2+) + pH <7.3 and/or bicarbonate <18 mmol/L
  • Anion gap is not a first-line diagnostic criterion (use if ketones unavailable)
Fluids
  • Isotonic crystalloid resuscitation first; correct hypovolemia before or alongside insulin
Potassium
  • Replace when K <5.0 to keep 4–5 mmol/L, provided urine output / renal function are adequate (reflexive KCl in AKI/anuria can cause hyperkalemia)
  • If K <3.5 at presentation, replace potassium and delay insulin until K >3.5 mmol/L. Check baseline, 2 h after insulin starts, then every 4 h
Bicarbonate
  • Routine bicarbonate is not recommended; consider only in severe acidosis (pH <7.0)
Correction endpoint vs resolution
  • The original SQuID order set steps down correction dosing around an anion gap ≤16 as an OPERATIONAL trigger (the order set guards against premature discontinuation) — this is NOT the ADA resolution definition
  • Continue insulin + dextrose until biochemical resolution: BHB <0.6 mmol/L AND (venous pH ≥7.3 OR bicarbonate ≥18 mmol/L); glucose <200 mg/dL is ideal but not required
  • ADA advises AGAINST using the anion gap as a resolution criterion (chloride shifts can normalize it while ketosis persists)
Transition
  • The 1–2 hour overlap rule (2 hours in the 2026 Standards) applies to giving SC basal insulin BEFORE discontinuing IV insulin, so the patient is never without active insulin. Follow the validated SQuID transition procedure for the SC pathway
Patient selection / exclusions
  • SQuID = uncomplicated mild-to-moderate DKA, alert, monitorable q2h
  • Severe DKA (any of: pH <7.0, bicarbonate <10 mmol/L, BHB >6 mmol/L, or stupor/coma) is excluded
  • Also exclude: shock/hemodynamic instability, HHS, pregnancy, euglycemic/SGLT2i DKA, pediatric patients, and the original SQuID exclusions (ESRD, heart failure, serious infection/sepsis, acute MI or high-risk cardiac disease, immunosuppression, or need for surgery). Those get an IV infusion with closer monitoring

Evidence

Overview of Evidence

Author, yearDesign, sample sizeIntervention & comparisonOutcome
Griffey (SQuID II), 2024Single-center prospective cohort
N = 84 (62 SQuID)		SC insulin pathway vs IV infusion (expanded eligibility)Time-on-protocol 10.4 h shorter; rescue dextrose 8% vs 18% (no statistically detected difference). ICU admission in mild-moderate DKA fell from 54% to under 21% (single-center, before/after, observational)
Griffey (SQuID I), 2023Single-center cohort
N = 177 (78 SQuID)		SC lispro pathway vs IV infusionReduced ED length of stay; no detected difference in rescue dextrose (safety)
Alnuaimi, 2024Meta-analysis
6 RCTs (245) + 4 obs (8,444)		SC vs IV insulinNo difference in mortality, resolution time, or hypoglycemia; LOS difference not significant. GRADE certainty moderate (hypoglycemia, resolution time, LOS), low (mortality), very low (hypokalemia)
Thammakosol, 2022Single-center open-label RCT
N = 60 (77% type 2 DM)		Early glargine 0.3 u/kg added to IV infusion (within 3 h) vs IV aloneFaster resolution (9.89 vs 12.73 h); shorter LOS; no excess hypoglycemia/hypokalemia (IV-adjunct trial; extrapolated to SC by analogy)
Andrade-Castellanos (Cochrane), 20165 RCTs, N = 201
low/very-low quality		SC rapid-acting analogues vs IV regularNeither advantage nor disadvantage for mild/moderate DKA (dated, pre-SQuID)
ADA consensus, 2024Consensus / practice guidelineDiagnosis, management, resolution of DKA/HHSRecognizes SC rapid-acting q1–2h for uncomplicated mild-moderate DKA; revised diagnostic and resolution criteria. Reaffirmed by the ADA Standards of Care 2026

Conclusions

  • Uncomplicated mild-to-moderate DKA in adults may not need an ICU bed or an insulin drip: the 2024 ADA consensus recognizes SC rapid-acting insulin q1–2h as an option, and SQuID cohorts report fewer ICU admissions with comparable safety, provided q1–2h monitoring is guaranteed (single-center, observational data). Write orders from your institution's validated order set, not this summary.
  • The SQuID approach: rapid-acting analogue about 0.2 u/kg SC per dose while glucose >250, step down to ~0.1 u/kg and start dextrose once glucose is 250 or below, about every 2 hours, holding/adjusting for hypoglycemia.
  • Two drug-safety rules do not change with the route: delay insulin until K >3.5 (with adequate renal function before repleting K), and add dextrose once glucose is 250 or below so insulin keeps clearing ketones.
  • Know the exclusions: severe DKA (pH <7.0, bicarbonate <10, BHB >6, or stupor/coma), shock, HHS, pregnancy, euglycemic/SGLT2i DKA, pediatrics, and the SQuID comorbidity exclusions belong on an IV drip with closer monitoring, not the SC pathway.
  • Resolution is ketone/acid-base, not glucose or a normalized anion gap: BHB <0.6 AND (pH ≥7.3 OR bicarbonate ≥18); give SC basal insulin 1–2 h before stopping any IV insulin to prevent rebound.

References

  • Umpierrez GE, Davis GM, ElSayed NA, et al. Hyperglycemic Crises in Adults With Diabetes: A Consensus Report. Diabetes Care. 2024;47(8):1257-1275. PMID: 39052901
  • American Diabetes Association Professional Practice Committee. 16. Diabetes Care in the Hospital: Standards of Care in Diabetes-2026. Diabetes Care. 2026;49(Suppl 1):S339-S355. PMID: 41358892
  • Griffey RT, Schneider RM, Girardi M, et al. SQuID (subcutaneous insulin in diabetic ketoacidosis) II: Clinical and operational effectiveness. Acad Emerg Med. 2025;32(1):61-71. PMID: 39308229
  • Griffey RT, Schneider RM, Girardi M, et al. The SQuID protocol (subcutaneous insulin in diabetic ketoacidosis): Impacts on ED operational metrics. Acad Emerg Med. 2023;30(8):800-808. PMID: 36775281
  • Alnuaimi A, Mach T, Reynier P, et al. Subcutaneous insulin versus continuous insulin infusion in managing adult diabetic ketoacidosis: a systematic review and meta-analysis. BMC Endocr Disord. 2024;24(1):133. PMID: 39090718
  • Thammakosol K, Sriphrapradang C. Effectiveness and safety of early insulin glargine in the management of diabetic ketoacidosis: a randomized controlled trial. Diabetes Obes Metab. 2023;25(3):815-822. PMID: 36479786
  • Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, Gonzalez-Padilla DA. Subcutaneous rapid-acting insulin analogues for diabetic ketoacidosis. Cochrane Database Syst Rev. 2016;(1):CD011281. PMID: 26798030
  • Rodriguez Alvarez P, San Martin VT, Morey-Vargas OL. Hyperglycemic crises in adults: A look at the 2024 consensus report. Cleve Clin J Med. 2025;92(3):152-158. PMID: 40032308
Tags:Diabetic Ketoacidosis Subcutaneous Insulin SQuID Protocol Endocrinology