Diabetes: RABBIT 2 (The Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes) (2007)

Question 1

RABBIT 2 Clinical Q

Answer 1

In non-critically ill inpatients with type 2 diabetes mellitus who were insulin-naive, is a basal-bolus insulin regimen more effective and safer for glycemic control as compared to sliding-scale regular insulin?

Question 2

RABBIT 2 Bottom Line

Answer 2

In non-critically ill inpatients with type 2 diabetes mellitus who were insulin-naive, a basal-bolus insulin regimen is more effective for glycemic control as compared to sliding-scale regular insulin. There were no significant differences in the incidence of hypoglycemia and length of stay between the two treatment strategies.

Question 3

RABBIT 2 Primary Outcome

Answer 3

Glycemic control as measured by the mean daily blood glucose concentration

Question 4

RABBIT 2 Inclusion Criteria

Answer 4

-Age 18-80 years who were insulin-naive -Non-surgical patients admitted to the general ward -Known history of diabetes >3 months -Blood glucose level between 140-400 mg/dl (7.8-22.2 mmol/L) on admission -Diabetes treatment with diet alone or any combination of oral antidiabetic agents

Question 5

RABBIT 2 Interventions

Answer 5

• Patients were randomized to receive basal-bolus insulin or SSI
• Oral antiglycemic agents were discontinued on admission
• Blood glucose level was measured using a glucose meter before each meal and at bedtime (or every 6 h if a patient was unable to eat)
• The target fasting and pre-meal blood glucose level was <140 mg/dl (<7.8 mmol/L)
• Basal-bolus regimen:
  
  • ​​For patients with blood glucose level between 140-200 mg/dl (7.8-11.1 mmol/L), total daily insulin dose of 0.4 units/kg was given
  • For those with glucose level between 201-400 mg/dl (11.2-22.2 mmol/L), total daily insulin dose of 0.5 units/kg was given Insulin glargine (Lantus) was given once daily (50% of total insulin dose), insulin glulisine (Apidra) was given in 3 equal doses before meals (50% of total insulin dose)
  • If a patient was unable to eat, the pre-meal insulin glulisine was withheld but the insulin glargine was administered If the fasting and pre-meal blood glucose levels were >140 mg/dl (>7.8 mmol/L), the daily dose of insulin glargine was increased by 20%
  • If a patient develops hypoglycemia (<70 mg/dl or <3.9 mmol/L), the daily dose of insulin glargine was reduced by 20%
  • Supplemental insulin glulisine was administered in addition to the scheduled pre-meal insulin if blood glucose >140 mg/dl (>7.8mmol/L)
• Sliding scale (SSI) regimen:
  
  • For patients who were unable to eat, regular insulin was administered every 6 hours, as per the “insulin sensitive” column
  • For patients able to eat, regular insulin was given before each meal and at bedtime, following the “usual” column
  • If fasting and pre-meal blood glucose levels are persistently >140 mg/dl (>7.8 mmol/L) without hypoglycemia, insulin scale was increased from the “insulin sensitive” to the “usual” column or from the “usual” to the “insulin-resistant” column
  • If a patient develops hypoglycemia (blood glucose <70 mg/dl or <3.9 mmol/L), insulin scale was decreased from “insulin-resistant” to “usual” column or from the “usual” to “insulin-sensitive” column If the mean daily blood glucose level was >240 mg/dl (13.3 mmol/L), or if 3 consecutive levels were >240 mg/dl (>13.3 mmol/L) on the maximal sliding-scale regime, patients were switched to basal-bolus regimen starting with total daily dose of 0.5 units/kg

Question 6

RABBIT 2 Criticisms

Answer 6

• Generalizability: Patients without documented DM before admission were excluded, and thus the trial likely disproportionately excluded patients with poor health literacy, poor access to care, or recent development of DM.
• Generalizability: Patients treated with insulin and corticosteroids were excluded due to the higher risk of hyperglycemia if they were treated with SSI.
• Clinical relevance: The study was not adequately powered to determine differences in mortality or clinical outcome between basal-bolus insulin regimen and SSI.
• Analysis unclear: There was crossover of 9 (14%) SSI patients to basal-bolus regimen; it is unclear if these were analyzed as intention-to-treat.
• Small sample size, conducted at only 2 sites, limits generalizability.
• There were significantly more males in the basal-bolus insulin group as compared to the SSI group (64.6% vs. 32.3%). However, the significance of this is unclear.
• The SSI group received a significantly less total daily insulin dose as compared to the basal-bolus group (12.5 vs. 42 units; P<0.001). It is unclear if the difference in insulin dose is related to the difference in outcomes observed between these treatments.