Table 2 Summary of outcomes assessing the use of subcutaneous insulin compared to intravenous insulin for the management of mild to moderate diabetic ketoacidosis (DKA)

Fischer et al. (1977)

N/A

N/A

N/A

No episodes of hypoglycemia.

4 cases of hypokalemia (uncertain which intervention group)

Authors report no significant difference between the two groups in terms of hypoglycemia and hypokalemia risks.

Umpierrez et al. (2004)

SC: 4 ± 2

IV Insulin: 4 ± 1

SC: 10 ± 3

IV Insulin: 11 ± 4

None

Hypoglycemia:

One in each group

Hypokalemia: N/A

No significant difference was found between the two groups in terms of major outcome variables. However, treatment of diabetic ketoacidosis in a non–intensive care setting (step-down unit or general medicine ward) was associated with a 39% lower hospitalization cost than was treatment with IV insulin in the ICU.

Umpierrez et al. (2004)

SC-1 h: 3.4 ± 3;

SC-2 h: 3.9 ± 5;

IV Insulin: 4.5 ± 3

SC-1 h: 10 ± 3;

SC-2 h: 10.7 ± 3;

IV Insulin: 11 ± 3

None

Hypoglycemia:

One in each group

Treatment of DKA with SC insulin analogs every 1–2 h represents a safe and effective alternative to treatment with IV regular insulin as no statistically significant differences were found among the 3 groups in terms of biochemical parameters, changes in plasma glucose, length of hospital stay, mortality, hypoglycemic events and recurrence of DKA

Ersöz et al. (2006)

N/A

L Group (SC Group):

Time to reach glucose < 200 mg/dL = 9.4 ± 8.9,

pH > 7.3 = 8.2 ± 5.6,

serum bicarbonate > 18mEq/L = 14.8 ± 7.0,

β-hydroxybutyrate < 0.6 mmol/L = 11.2 ± 4.9 and urine ketones negative = 17.2 ± 7.0;

R Group (IV Insulin):

Time to reach glucose < 200 mg/dL = 12.7 ± 7.5, pH > 7.3 = 6.8 ± 5.7, serum bicarbonate > 18mEq/L = 13.2 ± 7.5, β-hydroxybutyrate < 0.6 mmol/L = 15.3 ± 8.7 and urine ketones negative: 22.3 ± 10.9

N/A

N/A

No significant difference between the two groups in terms of rate of decline of plasma glucose, Beta-hydroxybutyrate, urinary ketone excretion, effective plasma osmolality and the mean duration of treatment until correction of the ketoacidosis. No serious side effects between the two groups. Total amount of insulin delivered was not different between the two groups.

Treatment of mild and moderate DKA with hourly SC insulin lispro administration represents a safe and effective alternative to IV regular insulin administration.

Karoli et al. (2011)

Group 1 (IV Insulin): 6.6 ± 1.5

Group 2 (SC Insulin): 6 ± 1.2

Group 1 (IV Insulin): 11 ± 1.6

Group 2 (SC Insulin): 12 ± 2.2

None

Hypoglycemia:

Group 1 (IV Insulin):

2 patients

Group 2 (SC Insulin):

1 patient

Hypokalemia:

N/A

No significant differences between the two groups were observed in terms of major primary outcomes. The patients with uncomplicated DKA under appropriate supervision and careful monitoring can be managed in medical wards or non-ICU setting.

Prasad et al. (2015)

SC-1 h: 6.2 ± 4;

SC-2 h: 5.9 ± 3;

IV Insulin: 6.8 ± 3

SC-1 h: 10.3 ± 3;

SC-2 h: 10.8 ± 3;

IV Insulin: 10.5 ± 3

None

None

The mean duration of treatment until

glucose concentration was < 13.8 mmol/L (< 250 mg/dL) was not statistically different between patients treated with SC-1 h

(6.8 ± 3 h) and SC-2 h (6.5 ± 3 h) or with IV regular insulin (6.9 ± 4 h). Similarly, the mean duration of treatment until resolution

of ketoacidosis was not statistically different among treatment groups 10.3 ± 3 h, 10.8 ± 3 h and 10.5 ± 3 h respectively.

Balili et al. (2017)

SC group: 5.22 (3–11)

IV Insulin group: 11.42 (4–28)

SC Insulin group: 24.11 ± 7.70

IV Insulin group: 25.67 ± 8.56

One died in SC insulin analogue group due to septic shock secondary to hospital-acquired infection.

Hypoglycemia:

SC group: 1 event

IV insulin group: 2 events

Hypokalemia:

Occurred more frequently in the IV group.

Length of hospital stay was significantly shorter by a mean of six days for those in the SC insulin group compared to those in the IV insulin group. Two patients (17%) in the IV insulin group and one patient (11%) in the SC insulin group developed hypoglycemia. One patient died in the SC insulin group due to septic shock secondary to a hospital-acquired infection.¹ Hypokalemia occurred more frequently in the IV insulin group (50%) compared to the SC insulin group (11%).

Rao et al. (2022)

Intervention Site: Overall mean hospital stay 64.6 h (Pre-implementation) and 56.2 h (Post-implementation);

Standard Care Sites: Overall mean hospital stay 62.5 h (Pre-implementation) and 58.5 h (Post-implementation)

Intervention Site: Time to glucose < 250 mg/dL = 9.5 h (Pre-implementation) and 11.3 h (Post-implementation);

Standard Care Sites: Time to anion gap < 16 = 9.4 h (Pre-implementation) and 9.4 h (Post-implementation)

Intervention Site: Mortality within 30 days 0 (Pre-implementation) and 1 (Post-implementation);

Standard Care Sites: Mortality within 30 days 48 (Pre-implementation) and 35 (Post-implementation)

Intervention Site: Direct admissions to ICU: (Pre-implementation: 202; Post-implementation: 34), Late admissions to ICU: (Pre-implementation: 6; Postimplementation:4);

Standard Care Sites: Direct admissions to ICU: (Pre-implementation: 3357; Post-implementation: 2488), Late admissions to ICU: (Pre-implementation, 64; Post-implementation, 45).

The SC insulin protocol was associated with a 57% relative decrease in ICU admissions at intervention sites and a 50% relative decrease in 30-day readmissions compared with standard care sites.

Stuhr et al. (2023)

SC: 3.4

IV Insulin (with bolus): 4.5

IV Insulin (without bolus): 6.5

SC: 12.7

IV Insulin (with bolus): 13.1

IV Insulin (without bolus): 13.9

N/A

Hypoglycemia:

SC: 45 events

IV Insulin (with bolus): 69 events.

IV Insulin (without bolus): 100 events

Hypokalemia:

N/A

Using a SC insulin protocol may be equally effective in treating mild to moderate DKA compared with an IV insulin infusion protocol, while also decreasing LOS and incidence of hypoglycemic events. With a reduction in LOS and the ability to successfully treat DKA outside of the ICU environment, utilization of a SC DKA treatment protocol in this population can potentially lead to reduced healthcare costs and increased ICU resources availability.

Griffey et al. (2023)

SQuID versus traditional during the study period: -3.0 (95% CI -8.5 to -1.4)

SQuID versus preintervention period: -1.4

(95% CI -3.1 to -0.1)

SQuID versus pre-COVID control period: -3.6 (95% CI -7.5 to -1.8)

N/A

N/A

N/A

Mild to moderate DKA can be managed on a non-ICU floor using subcutaneous insulin injections instead of a traditional insulin drip – known as the SQuID protocol, however more data are needed from other sites to address the safety and efficacy. ED LOS was statistically shorter in patients treated with SQUiD protocol compared to the traditional protocol. Decrease in ICU admissions across all mild to moderate DKA patients was seen over time with no statistical difference between intervention period to pre-intervention and pre-COVID periods.