Subcutaneous Versus Intravenous Insulin for Treatment of Diabetic Ketoacidosis
Date First Published:
November 29, 2025
Last Updated:
November 29, 2025
Report by:
Darian Mills MD, Thomas Peterson MD, Senior EM Resident, EM Faculty (Corewell Health/Michigan State University Emergency Medicine Residency Program)
Search checked by:
Jeffrey Jones MD, Research Director
Three-Part Question:
In [adults with mild to moderate diabetic ketoacidosis] does [subcutaneous insulin] compared to [intravenous insulin] lead to [increased mortality or increased length of hospital stay]?
Clinical Scenario:
A 42-year-old man with past medical history of Type II diabetes presents to the emergency department for nausea and vomiting. Despite first-line antiemetics, he continues to experience nausea and vomiting. Initial lab workup demonstrates an initial blood glucose of 325, pH of 7.15, bicarbonate of 14, elevated serum and urine ketones, and an anion gap of 18. You consider whether this patient’s condition could be treated with subcutaneous insulin rather than intravenous insulin infusion.
Search Strategy:
Medline 1966-10/25 using PubMed, Cochrane Library (2025), and Embase
Search Details:
[(subcutaneous insulin) AND (intravenous insulin) AND (diabetic ketoacidosis)]. Limit to adults, English language, meta-analysis
Outcome:
One recent meta-analysis was identified that answered the clinical question.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| A systematic review and meta-analysis comparing outcomes between using subcutaneous insulin and continuous insulin infusion in managing adult patients with diabetic ketoacidosis Alnuaimi A, Mach T, Reynier P, et al August 2024 Canada | Six RCTs (245 participants) and four observational studies (8444 patients) assessed the use of subcutaneous compared to intravenous insulin for the treatment of mild to moderate DKA . | Meta-analysis to determine the safety and efficacy of using subcutaneous insulin compared to an intravenous (IV) insulin infusion in managing adults with diabetic ketoacidosis (DKA). | Length of hospital stay, time to resolution of DKA, cost of hospitalization, and complications | Some studies showed a decreased length of stay (Mean Difference [MD] in days: -0.39) among individuals treated with subcutaneous insulin compared to intravenous insulin. There was no difference in the risk of | The sample sizes of the retrieved studies were relatively small with no follow-up data available to assess outcomes after discharge. More patients received intravenous insulin as opposed to subcutaneous, there were no documented cases of euglycemic diabetic ketoacidosis, and there was a lack of differentiation regarding the underlying trigger for diabetic ketoacidosis. The included studies varied significantly in the subcutaneous insulin protocols, with protocols differing regarding the dosing and timing of dosages. No sensitivity analyses were performed to determine how each randomized controlled trial influenced the overall outcome. this single study also included 2,963 patients categorized as having “severe” diabetic ketoacidosis, which is not the intended patient population under investigation. in the meta-analysis. |
| all-cause mortality, time to resolution of DKA (MD in hours: 0.17) and | |||||
| hypoglycemia (Risk Ratio [RR]: 1.02) between the two groups. |
Author Commentary:
This meta-analysis did not identify important differences in overall mortality and adverse outcomes following treatment of mild-to-moderate DKA with subcutaneous insulin compared to a continuous IV insulin infusion.
Bottom Line:
In adults with mild to moderate diabetic ketoacidosis, subcutaneous insulin compared to intravenous insulin shows no difference in mortality, time to resolution of DKA, or hypoglycemia, and may be associated with decreased length of hospital stay. The quality of evidence was overall very low to moderate for the outcomes assessed due to the limited number of studies and potential bias. Further studies are necessary to determine the effectiveness and safety of using subcutaneous insulin in the treatment of DKA in specific populations, such as during pregnancy, in cases of euglycemic DKA, and in severe DKA.
Level of Evidence:
Level 1: Recent well-done systematic review was considered or a study of high quality is available
References:
- Alnuaimi A, Mach T, Reynier P, et al. A systematic review and meta-analysis comparing outcomes between using subcutaneous insulin and continuous insulin infusion in managing adult patients with diabetic ketoacidosis