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1. RABBIT 2
SUMMARIZED BY DR. MARIA MORKOS
Umpierrez, et al. “Randomized study of basal bolus
insulin therapy in the inpatient management of
patients with Type 2 Diabetes (RABBIT 2 Trial).”
Diabetes Care. 2007. 30:2181-2186.

2. Randomized Study of Basal Bolus Insulin Therapy in the Inpatient
Management of Patients with Type 2 Diabetes (RABBIT 2)
Summarized by: Maria Morkos, MD; Laxmi Suthar, MD

3. BACKGROUND
 Hyperglycemia is associated with increased
clinical complications such as prolonged hospital
stay, risk of infection, and mortality
 Prior research had looked at hyperglycemia in
critically ill/ICU patients
 Hyperglycemia has been frequently overlooked
on the inpatient medicine and surgery services
 Many reports have shown that most hospitalized
patients are treated with SSI; less than half have
basal insulin prescribed
 Few clinical trials have focused on the optimal
management of inpatient hyperglycemia in the
noncritical setting

4. CLINICAL QUESTION
How does a basal/bolus insulin regimen compare
to sliding scale regular insulin in patients with
type 2 diabetes in terms of efficacy and safety?

5. DESIGN
 Trial Design: randomized, open label, multicenter (Emory University
and University of Miami)
 N=130
 Glargine daily + glulisine TID (n=65)
 Adjustable regular SSI (n=65)
 Primary outcome: mean daily blood glucose
 Secondary outcomes: hypoglycemia, length of stay, mortality

6. POPULATION
Inclusion Criteria
 Insulin naïve pts with type 2 diabetes for
at least 3 months
 Admission blood glucose 140-180
mg/dL
 Admitted to inpatient medical unit
Exclusion Criteria
 New onset diabetes
 Prior insulin use
 Steroid use
 DKA/HHS
 ICU admission
 Liver disease
 Cr > 3mg/dL
 Impaired mental status
 Pregnancy

7. INTERVENTIONS
 Patients randomly assigned to either:
 Glargine daily + glulisine TID, or
 Regular sliding scale insulin
 Unblinded study
 Power calculations not specified (and unclear how pts were screened and
excluded)

8. RESULTS
 Mean daily glucose was 27 mg/dL lower in the basal-bolus group (p < .01)
 BG target of <140 mg/dL was achieved in 66% of patients in basal-bolus
group
 Same BG target of <140 was achieved in 38% of patients in SSI group
 No significant difference in length of hospital stay between the two groups
 3% hypoglycemia (BG< 60) in both groups
 One patient death in basal-bolus group

9. CRITICISMS/LIMITATIONS/FUNDING
 Not powered to detect a mortality difference between treatment groups
 Study was unblinded; sample size small with unspecified power calculations
 Excluded pts with known history of diabetes, which make up a large percentage of
hospitalized pts
 Excluded pts treated with insulin and corticosteroids b/c they were considered at higher
risk of severe hyperglycemia if treated with SSI
 Other insulin regimens were not investigated
 Funding: manufacturer of Lantus (Sanofi-Aventis)

10. BOTTOM LINE
Treatment with basal-bolus
insulin resulted in improved
glycemic control compared to
treating with only SSI.
- No major difference in episodes
of hypoglycemia
- No major difference in length of
hospital stay

11. DISCUSSION QUESTIONS
 What insulin regimen in the inpatient setting can provide improved
glycemic control, based on the RABBIT 2 trial?
 What BG value did the study target for medicine inpatients?
 There were two clinical outcomes that resulted the same for both arms
of the trial; what were they?

12. DISCUSSION ANSWERS
 What insulin regimen in the inpatient setting can provide improved glycemic control,
based on the RABBIT 2 trial?
 ANSWER: Long acting Lantus with mealtime insulin (in this trial, they tested
glulisine=regular insulin)
 What BG value did the study target for medicine inpatients?
 ANSWER: BG <140
 There were two clinical outcomes that were the same for both arms of the trial; what were
they?
 ANSWER: Episodes of hypoglycemia and length of stay

13. BOARD-LIKE QUESTION
25 yo F with PMH sig for only T1DM is
evaluated for new glycemic fluctuations. Her
A1c levels since dx 3 years ago ranged from
6.2% to 7.3%, with the most recent being
7.3%. She recently started a new high
demand job but continues to eat a carb
consistent diet that does not change from
day to day; she also continues to exercise
daily. Her insulin regimen is glargine once
daily and insulin lispro TID.
VS, PE wnl.
eGFR, Cr, and urine albumin:Cr ratio all wnl.
Her breakfast glucose values are 101-126;
lunch BG 92-190; dinner BG 102-204;
bedtime BG 72-210.
QUESTION
Which of the following is most likely causing
the fluctuating glycemic control?
A. Antibodies to exogenous insulin
B. Gastroparesis
C. Inadequate insulin doses
D. Inappropriate insulin timing

14. BOARD-LIKE QUESTION
QUESTION
Which of the following is most likely causing
the fluctuating glycemic control?
A. Antibodies to exogenous insulin
B. Gastroparesis
C. Inadequate insulin doses
D. Inappropriate insulin timing
Educational Objective:
Evaluate timing of prandial insulin in a pt
with DM
Key Point:
- Meal coverage with insulin should mimic
the physiologic pattern seen with
endogenous insulin secreted from the
pancreatic beta cells
- Insulin administration should therefore be
prior to or at the time of meal
consumption

15. BOARD-LIKE QUESTION
A 57-year-old man is admitted to the
hospital for evaluation of substernal chest
pain. His medical history is significant for
type 2 diabetes mellitus, coronary artery
disease, hypertension, and hyperlipidemia.
He manages his diabetes as an outpatient
with diet, exercise, and metformin. His other
medications are aspirin, metoprolol,
atorvastatin, and sublingual nitroglycerin as
needed. His inpatient plasma glucose values
are 170 to 210 mg/dL (9.4-11.6 mmol/L).
Results of all other laboratory studies are
normal.
(Adapted from MKSAP 17)
QUESTION
Which of the following is the most
appropriate treatment for this patient's
diabetes while hospitalized?
A. Basal and prandial insulin
B. Glipizide
C. Metformin
D. Sliding-scale insulin

16. BOARD-LIKE QUESTION
ANSWER
Which of the following is the most
appropriate treatment for this patient's
diabetes while hospitalized?
A. Basal and prandial insulin
B. Glipizide
C. Metformin
D. Sliding-scale insulin
Educational Objective:
Manage diabetes in a hospitalized patient
Key Point:
- For non-critically ill hospitalized patients
with diabetes mellitus and hyperglycemia,
a weight-based treatment plan that
includes basal and prandial insulin is
recommended.

17. REFERENCES
 Effects of intensive glucose lowering in Type 2 Diabetes (2008). New England Journal of Medicine,
358:2545.-2559. doi 10.1056/NEJMoa0802743
 Hunt, D, et al. The Evidence. Revised ed. Selected Nights; 2004: 77.