In the last article of “Critical Care Time,” I discussed Tips and Tricks for Managing Patients with Diabetic Ketoacidosis (DKA) in the Emergency Department (ACEP Now, February 2026).

Depending on your catchment area and patient population, your emergency department (ED) may see children or adolescents with a new diagnosis of diabetes presenting with profound DKA, or you may have an older nursing home population with a high prevalence of hyperosmolar hyperglycemic state. However, if your shop is anything like mine, the bread-and-butter presentation of hyperglycemic emergencies is a patient who otherwise missed a dose of their long-acting insulin and presents in mild-to-moderate DKA.

With ED boarding at an all-time high and hospitals at capacity, the treatment and disposition of these patients can be difficult. Sure, you can start an insulin drip and admit them to the intensive care unit (ICU), but by the time the ICU has accepted the patient, report has been called, and transport brings the patient upstairs, many patients with mild DKA may be close to having the acidosis resolve and could probably be discharged shortly after arrival to the unit. That is arguably a suboptimal use of resources. If you don’t have an ED-based ICU to manage these patients, the answer might be a subcutaneous DKA protocol.¹ Let’s take a deeper dive.

Insulin Is Insulin

When I was an intern, I felt overwhelmed learning about insulin. Not only were the names confusing (wait, there’s a difference between Humulin R, Humulin N, and Humulin 70/30? And Humalog is different?), but it also seemed like memorizing the equivalent doses and pharmacology would be impossible. In their seemingly infinite wisdom, my senior resident taught me, “a unit of insulin is a unit of insulin,” meaning that every formulation of insulin is different only in how rapidly it is available to the body.

Figure 1. Insulin release over time by type of insulin. IV regular insulin is not shown here but would be even shorter than the ultra-rapid acting insulin, with a duration of about six minutes. (Created by the author using the AI tool Google Gemini. Click to enlarge.)

Ultra-short-acting insulin like lispro or aspart may have action only over an hour or so, while long-acting insulin like glargine may deliver the same amount of insulin over a day. And consider insulin icodec, which delivers the same amount insulin over the span of a week. ² (Figure 1). For example, 12 units of lispro will be delivered over about an hour, whereas those same 12 units as glargine are delivered as about a half unit per hour over a day. (Here, we have to acknowledge that the duration is not exact, and there will be slight differences between patients and formulations.)

In contrast to subcutaneous insulin, where the duration of action is measured in hours to days, intravenous (IV) insulin is incredibly short-acting, with an elimination half-life measured in minutes.³ So why has it been preferred in DKA? The current consensus guidelines published in 2024 cite the 2009 guideline as their rationale for the choice of IV insulin, which recommended it “because of its short half-life and easy titration and the delayed onset of action and prolonged half-life of subcutaneous regular insulin.”^4,5

At the same time, however, they admit that “insulin therapy is effective regardless of the route of administration” and cite a nearly 50-year-old study—published by the senior author of the guidelines—to support this recommendation without addressing newer ultra-short-acting insulins.⁶

So, when should we choose IV, and when is subcutaneous a better choice? I have not heard of any DKA protocol that involves glucose checks more frequently than hourly, so I’m not sure that the easy titration is that compelling a rationale, particularly because most institutions rely on a fixed 0.1units/kg/hr rate. In severe DKA, however, the patient will likely have significant hypovolemia and dehydration, in addition to profound acidosis—if not frank shock—making subcutaneous absorption irregular. For these patients, a continuous infusion of insulin is reliable and allows for rapid adjustment. For all others, we can make a case for subcutaneous management.

Subcutaneous Management

The 2024 consensus guidelines offer subcutaneous insulin as a treatment option for mild DKA, which they define as a glucose level ≥200 mg/dL, a β-hydroxybutyrate level of 3.0–6.0 mmol/L, and a pH >7.25 with a bicarbonate of 15–18 mmol/L. If you accept my thesis that the only clinically important difference between forms of insulin is the duration of action, these guidelines drive home the point (Figure 2): Instead of an IV loading dose of 0.1 units/kg of regular insulin, they recommend a subcutaneous dose of 0.1 units/kg of rapid-acting insulin. Then, instead of a continuous IV infusion of 0.1 units/kg/hr of regular insulin, they substitute 0.1 units/kg of rapid-acting insulin given subcutaneously every hour. Finally, when the glucose is < 250mg/dL, they recommend spacing to 0.1 units/kg subcutaneously every two hours, instead of a continuous infusion of 0.05 units/kg/hr.

The 2024 consensus guidelines offer subcutaneous insulin as a treatment option for mild DKA.

Here, it seems they have made a concession to convenience—rather than giving 0.05 units/kg subcutaneously every hour—which I appreciate. The exact same dose of insulin is given at every step, just as a subcutaneous bolus at the start of the hour rather than a continuous infusion given throughout the hour.

Figure 2. A comparison of subcutaneous and intravenous treatment strategies, showing the similarities. Figure adapted from Umpierrez et al., Diabetes Care; 2024;47(8):1257-1275. (Click to enlarge.)

Other than the consensus guidelines, the study that I have seen most commonly cited in the ED to justify a subcutaneous approach is the SQuID protocol.⁷ The SQuID protocol, derived from a single-center study and published in an emergency medicine journal, used a protocol that varied the dose of insulin by the blood glucose. For glucose levels ≥ 250 mg/dL, they recommended a dose of insulin lispro 0.2 units/kg, and for glucose levels < 250 mg/dL, they used a dose of 0.1 units/kg. Glucose was then checked every two hours, and the next insulin was based on that subsequent glucose value. Other protocols have been published, some with higher loading doses such as 0.3 units/kg or 0.15 units/kg.^8-10  In each of these studies, subcutaneous management compared well to traditional IV management, typically with a shorter ED and hospital lengths of stay.

A recent review concludes that subcutaneous management “may be as safe and effective as IV therapy … [and is] associated with the conservation of resources.”¹¹ To my knowledge, no studies have compared any of these regimens head-to-head, and while some included “moderate” DKA, none included severe DKA. However, for the typical patient presenting with mild-to-moderate DKA, a subcutaneous management seems like a useful tool to have in your back pocket, especially when the hospital is full.

Dr. Jansson is the medical director of the emergency critical care center (EC3), director of operations for the division of critical care, and an assistant professor of emergency medicine and internal medicine at the University of Michigan.

References

1. Haas NL, Whitmore SP, Cranford JA, et al. An Emergency Department-Based Intensive Care Unit is Associated with Decreased Hospital and Intensive Care Unit Utilization for Diabetic Ketoacidosis. J Emerg Med. 2020 Apr;58(4):620–626.
2. Schaffner H, Wiener J, DeLuca A, et al. Insulin icodec: A novel once-weekly treatment for diabetes. Diabet Med. 2024;41(10).
3. Lin S, Chien YW. Pharmacokinetic-pharmacodynamic modelling of insulin: comparison of indirect pharmacodynamic response with effect-compartment link models. J Pharm Pharmacol. 2002;54(6):791–800.
4. Umpierrez GE, Davis GM, ElSayed NA, et al. Hyperglycemic Crises in Adults With Diabetes: A Consensus Report. Diabetes Care. 2024 Aug 1;47(8):1257–1275.
5. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335–1343.
6. Fisher JN, Shahshahani MN, Kitabchi AE. Diabetic Ketoacidosis: Low-Dose Insulin Therapy by Various Routes. New England Journal of Medicine. 1977;297(5):238–241.
7. 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.
8. Karoli R, Fatima J, Salman T, et al. Managing diabetic ketoacidosis in non-intensive care unit setting: Role of insulin analogs. Indian J Pharmacol. 2011;43(4):398–401.
9. Umpierrez GE, Latif K, Stoever J, et al. Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. American Journal of Medicine. 2004;117(5):291–296.
10. Ersöz HÖ, Ukinc K, Köse M, et al. Subcutaneous lispro and intravenous regular insulin treatments are equally effective and safe for the treatment of mild and moderate diabetic ketoacidosis in adult patients. Int J Clin Pract. 2006;60(4):429–433.
11. Ibarra F, Bae R, Haghighat B. Review of Subcutaneous Insulin Regimens in the Management of Diabetic Ketoacidosis in Adults and Pediatrics. Ann Pharmacother. 2025;59(3):277–288.