SGEM#511: I’d Like To Treat, DKA with the SQuID Protocol

Date: May 20, 2026 Guest Skeptic: Dr. Matt McArthur is an ED Physician working primarily in Guelph and Kitchener with occasional rural locums in the small town of Walkerton, where he grew up. His clinical interests include POCUS, emergency cardiology, QI, knowledge translation, motivational interviewing, and vertigo. He is very active in medical education, including as a clinical skills and POCUS instructor, a Contributing Editor with the EMCases Podcast, and Regional Education Lead for Undergraduate Family Medicine at the Waterloo Regional Campus of McMaster University. Reference: Qiang et al. Safety and Effectiveness of Subcutaneous Insulin for Management of Mild to Moderate Diabetic Ketoacidosis in Non-Pregnant Patients: A retrospective cohort study at a tertiary care centre. Canadian Journal of Diabetes. Oct 2025 Case: A 56-year-old woman with insulin-treated type 2 diabetes presents to the emergency department (ED) with 24 hours of nausea, vomiting, polyuria, and weakness after missing insulin doses during a viral illness. She is alert, mildly tachycardic, normotensive, breathing slightly fast, and appears dry but not toxic. Her labs show glucose 23 mmol/L, pH 7.26, bicarbonate 14 mmol/L, an anion gap of 22, and positive serum ketones. You diagnose her with diabetic ketoacidosis (DKA). After initial IV fluids, she has clinically improved and does not require any vasopressors or airway support. The practical question is whether she really needs an intravenous (IV) insulin drip and intensive care unit (ICU)-level care, or whether a structured subcutaneous (SC) insulin pathway would be safe and effective. Background: DKA is one of the classic endocrine emergencies that lands squarely in the wheelhouse of emergency medicine. It is a state of insulin deficiency that leads to progressive dehydration, electrolyte deficits, and acidemia, which together can be fatal if untreated. Clinically, these patients show up with some combination of polyuria, polydipsia, nausea, vomiting, abdominal pain, tachypnea or Kussmaul respirations, dehydration, and sometimes altered mental status. Since the discovery of insulin by Fredrick Banting in Toronto in 1921, the treatment of DKA has changed dramatically in the last 100 years. Prior to insulin, the mortality from DKA was thought to exceed 95%. In modern times, the mortality is less than 1%. As a reminder, Sir Frederick Banting, Charles Best and James Collip, sold the patent for insulin to the University of Toronto for just $1 in January 1923. Banting famously stated, “Insulin does not belong to me, it belongs to the world”. DKA treatment involves protocol-based care, including IV rehydration to address hypovolemia; insulin therapy to stop ketoacidosis and restore normal metabolism; electrolyte and dextrose replacement to correct deficits, with regular monitoring of glucose and electrolytes (especially potassium) during treatment. Most hospitals have labour-intensive DKA protocols involving IV insulin infusion, which often require patients to be admitted to the ICU due to high nursing demands. However, with the introduction of rapid-acting subcutaneous (SC) insulin analogues in the late 1990s, such as insulin lispro and aspart, some clinicians have evaluated the use of rapid-acting SC insulin boluses as an alternative to IV infusion. SGEM has already dipped a toe into these waters in SGEM#414, which covered the SQuID protocol. That episode asked whether adults with mild-to-moderate DKA could be treated with fast-acting subcutaneous insulin on a non-ICU floor, resulting in shorter ED length of stay. That study by Griffey et al in AEM highlighted the operational appeal of avoiding an insulin drip and an ICU bed for every uncomplicated DKA patient. Between 2004 and 2016, six small randomized controlled trials found no difference in safety between SC insulin boluses and IV infusions in adults. Given the safety evidence and out of a desire to provide more efficient DKA care and avoid unnecessary ICU admissions, some hospitals have designed and implemented SC insulin-based treatment protocols as a first-line option for uncomplicated DKA patients and have published their outcomes in the medical literature. In the last five years, several observational studies have been published reporting patient and operational outcomes after implementation of a hospital-wide SC DKA protocol. That includes SQuID I by Griffey et al (SGEM#414), as well as SQuID II, which provided a further report on outcomes in the same hospital in St Louis. Additionally, we have seen Rao's 2022 report on their protocol introduced at Kaiser Permanente San Jose, Stuhr et al. in 2023 from Utah, and Ibarra et al. in Fresno in 2026. There were also Diabetes Consensus Guidelines published in 2024 that endorse the use of SC insulin in DKA. Clinical Question: In nonpregnant adults with mild to moderate DKA, is SC insulin a safe and effective alternative to IV insulin for DKA management? Reference: Qiang et al. Safety and Effectiveness of Subcutaneous Insulin for Management of Mild to Moderate Diabetic Ketoacidosis in Non-Pregnant Patients: A retrospective cohort study at a tertiary care centre. Canadian Journal of Diabetes. Oct 2025 Population: Nonpregnant adults aged 18 years or older admitted with mild or moderate DKA defined as an elevated urinary or serum ketones plus at least two of: pH 12 mmol/L, or glucose >14 mmol/L; euglycemic DKA could have relatively normal glucose.  Excluded: Severe DKA or unknown DKA severity, insufficient data, incomplete treatment, patients treated with both IV and SC insulin, insulin pump cases, pregnancy, reduced consciousness (GCS 160 kg. Patients not eligible for the SC protocol also included those with these higher-acuity features.  Intervention/Exposure: SC insulin protocol: glargine 0.3 U/kg (or home dose) plus aspart 0.2 U/kg every 4 hours unless glucose fell below 14 mmol/L, with glucose checks every 2–4 hours and electrolytes/blood gas every 4 hours; fluids and replacement per treating physician.  Comparison: Standard IV insulin treatment.  Outcome: Primary Outcome: Co-primary outcomes were time to anion-gap closure and hospital length of stay (LOS). Secondary Outcomes: Hypoglycemia, hypokalemia, and anion-gap acidosis requiring intervention within 24 hours.  Type of Study: Retrospective cohort study. Authors’ Conclusions: “These results suggest SC insulin is safe. Although it may take 8.4 hours longer to close the AG with SC insulin, there is less hypoglycemia and hypokalemia and no difference in LOS in hospital.”  Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Yes Was the exposure accurately measured to minimize bias? Yes Was the outcome accurately measured to minimize bias? Unsure Have the authors identified all-important confounding factors? No Was the follow-up of subjects complete enough? Yes How precise are the results? Unsure Do you believe the results? Yes Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Yes Funding of the Study? It was supported by a Quality Improvement Grant from Banting and Best Diabetes Centre Innovative Diabetes. Did the authors declare any conflicts of interest? None were declared. Results: The final cohort included 153 unique admissions: 92 treated with IV insulin and 61 with SC insulin. The mean age was about 57 years in both groups. Women made up 53% of the IV group and 54% of the SC group. Type 2 diabetes predominated (65% IV, 69% SC), with type 1 diabetes making up about one-third (33% IV, 31% SC). Euglycemic DKA was present in 24% of IV-treated patients and 16% of SC-treated patients. The IV group appeared sicker at baseline, with more moderate DKA (37% vs 11%), more renal dysfunction (33% vs 13%), and more neurologic dysfunction (17% vs 3%). About 30% of the cohort was taking an SGLT2 inhibitor.  Key Result: IV insulin closed the anion gap more quickly, but SC insulin caused less hypoglycemia and hypokalemia, with no meaningful difference in hospital length of stay or in anion-gap reopening requiring intervention. Primary Outcomes: IV insulin was faster to close the anion gap: adjusted median 15.6 hours versus 24.0 hours for SC, with an adjusted hazard ratio of 0.65 (95% CI 0.45 to 0.92; p=0.02) There was no statistically significant difference in hospital LOS: adjusted relative risk 0.83 (95% CI 0.61 to 1.13; p=0.24).  Secondary Outcomes: 1a. Confounding by Indication: Treatment was not randomized; the treating physician chose IV or SC insulin. In a cohort study, the exposed and comparison groups should have the same prognosis if we want a minimally biased estimate of the effect. Here, the IV group was clearly sicker at baseline, with more moderate DKA, more renal dysfunction, and more neurologic dysfunction. Multivariable adjustment helps, but no regression model can fully remove bias from unmeasured or poorly measured prognostic differences in a retrospective cohort study. 1b. Critical Appraisal of a Hospital Implementation/Quality Improvement (QI) Study: This is an observational study in which the authors retrospectively report on outcomes in their hospital after they introduced a new treatment protocol. So, we must appraise it for what it is, and not read it like an RCT. Observational studies, particularly QI/implementation studies like this one, generally aim to determine whether a given intervention in a specific healthcare setting was feasible and effective. QI studies are highly specific to the site where they took place. ...