Slide 1: Insulin in inpatients: basal bolus vs sliding scale. The RABBIT 2 Trial (2007).

Slide 2: Why? To ascertain efficacy and safety of basal-bolus vs. sliding scale insulin (SSI) monotherapy for glycemic control in the non-critical inpatient setting. Glargine/Glulisine vs regular insulin

Primary outcome – daily average blood glucose. Second outcomes – rates of hypoglycemia (<60 mg/gL), severe hyperglycemia (persistently >240 mg/dL), length of stay in hospital, mortality.

Slide 3: How? Study population: One. insulin-naive, non-critically ill T2DN patients admitted to medicine wards. Two. Ages 18-80. Three. Glucose between 140-400 mg/dL on admission.

130 patients randomized. 65 received basal-bolus. Total daily dose = 0.4-0.5 units/kg weight (divided equally between basal and continuous doses). 65 received sliding scale. Patients were divided into groups. “Usual,” “insulin-sensitive,” and “insulin resistant.” The units of insulin given is determined by group and BG.

Slide 4: Results. Basal bolus insulin vs. sliding scale insulin. Basal bolus resulted in lower mean fasting glucose and more patients meeting glycemic target while sharing similar risk of hypoglycemia as SSI.

Graphic showing the results for basal bolus insulin versus sliding scale insulin. Results include mean daily blood glucose, mean fasting glucose, % of patients achieving target glucose <140 mg/dL, # patients with hyperglycemia, # of patients with hypoglycemia, mean hospital length of stay, and deaths. Slide 5: So? Author's say: "basal-bolus insulin algorithm using insulin glargine once daily and insulin glulisine before meals represents a simple more effective regimen than SSI for glucose control in non-critically ill patients with type 2 diabetes." What do the critics say? The limited number of subjects studied did not allow for detection of mortality differences in basal-bolus vs. SSI. Despite the difference in primary outcome (mean blood glucose level) what does this ultimately mean for the patient? Are they experiencing better subjective quality of recovery/living? Was intention-to-treat analysis performed for patients who crossed over from SSI to basal-bolus? The trial design involved the discontinuation of oral hypoglycemic agents (SOC at the time). Now that certain oral agents are continued during hospital stay, is there a need for an updated trial? Check out CORE IM's "Mind the Gap" episode on inpatient oral diabetes medications for deeper learning! Interested in the prequel or sequel? Prequel: Strict vs standard glycemic control in CABG patients by Lazer et al, Circulation (2004). Sequel: RABBIT-2 Surgery study by Umpierrez et al, Diabetes Core (2011).

References

  • Umpierrez GE, Smiley D, Zisman A, Prieto LM, Palacio A, Ceron M, Puig A, Mejia R. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. 2007 Sep;30(9):2181-6. PMID 17513708.
  • Ambrus DB, O’Connor MJ. Things We Do For No Reason: Sliding-Scale Insulin as Monotherapy for Glycemic Control in Hospitalized Patients. J Hosp Med. 2019 Feb 1;14(2):114-116. PMID 30534639.
  • [Cho DH, Joo HJ, Kim MN, Kim HD, Lim DS, Park SM. Longitudinal Change in Myocardial Function and Clinical Parameters in Middle-Aged Subjects: A 3-Year Follow-up Study. Diabetes Metab J. 2021 Sep;45(5):719-729. PMID 34126709.
  • Johnson JD. On the causal relationships between hyperinsulinaemia, insulin resistance, obesity and dysglycaemia in type 2 diabetes. Diabetologia. 2021 Oct;64(10):2138-2146. PMID 34296322.

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