Sitagliptin Therapy in Hospitalized Patients With Type 2 Diabetes

Overview[ - collapse ][ - ]

Purpose High blood glucose levels in hospitalized patients with diabetes are associated with increased risk of medical complications and death. Improved glucose control with insulin injections may improve clinical outcome and prevent some of the hospital complications. Glargine (Lantus®) insulin injection is the most common treatment of diabetes in the hospital. Sitagliptin (Januvia®)is effective in lowering blood glucose. In a recent pilot study aiming to determine differences in glycemic control between treatment with sitagliptin (Januvia®) alone or in combination with basal insulin and basal bolus regimen in general medicine and surgery patients with type 2 diabetes (T2D). The investigators found that treatment with sitagliptin alone or in combination with basal insulin resulted in similar glycemic control compared to basal bolus regimen. The investigators will conduct a prospective RCT aimed to determine the safety and efficacy of sitagliptin therapy for in-hospital and post-discharge management of general medicine and surgical patients with T2D. A total of 280 patients with known history of diabetes will be randomized to receive sitagliptin plus basal (glargine) insulin once daily (group 1), or basal bolus regimen with glargine once daily and aspart or lispro insulin before meals (group 2). If needed, patients in the treatment groups will receive correction doses of rapid-acting insulin in the presence of hyperglycemia (BG > 140 mg/dl). The overall hypothesis is that treatment with sitagliptin in combination with basal insulin in patients with type 2 diabetes will result in a similar improvement in hospital and post-discharge glycemic control and in a lower frequency of hypoglycemic events than treatment with basal bolus insulin regimen with glargine once daily and lispro insulin before meals. Patients will be recruited at Grady Memorial Hospital, Emory University Hospital, University of Michigan, Ohio State University and Florida Hospital Diabetes institute
ConditionType 2 Diabetes
InterventionDrug: Sitagliptin + glargine
Drug: Basal Bolus
Drug: Metformin and sitagliptin
Drug: Metformin and sitagliptin + glargine 50%
Drug: Metformin and sitagliptin + glargine 80%
PhasePhase 4
SponsorEmory University
Responsible PartyEmory University
ClinicalTrials.gov IdentifierNCT01845831
First ReceivedApril 30, 2013
Last UpdatedOctober 30, 2013
Last verifiedOctober 2013

Tracking Information[ + expand ][ + ]

First Received DateApril 30, 2013
Last Updated DateOctober 30, 2013
Start DateJuly 2013
Estimated Primary Completion DateDecember 2016
Current Primary Outcome MeasuresGlycemic control [Time Frame: During hospitalization, average 5 days] [Designated as safety issue: No]The primary outcome of the study is to determine differences in glycemic control as measured by mean daily BG concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with T2D
Current Secondary Outcome Measures
  • Hypoglycemia [Time Frame: During hospitalization, average 5 days] [Designated as safety issue: Yes]Number of hypoglycemic events (<70 mg/dl) and severe hypoglycemic events (<40 mg/dl)
  • Hyperglycemia [Time Frame: During hospitalization, average 5 days] [Designated as safety issue: Yes]Number of episodes of hyperglycemia (BG > 300 mg/dl) after the first day of treatment
  • Total daily insulin dose [Time Frame: During hospitalization, average 5 days] [Designated as safety issue: No]Daily insulin requirement (unit/day) and number of insulin injections
  • Days of hospitalization [Time Frame: During hospitalization, average 5 days] [Designated as safety issue: No]Length of hospital stay
  • ICU need [Time Frame: During hospitalization, average 5 days] [Designated as safety issue: No]Need for ICU care (transfer to ICU)
  • Composite of hospital complications [Time Frame: During hospitalization, average 5 days] [Designated as safety issue: No]Differences between groups on a composite of hospital complications including pneumonia, wound infections, bacteremia, respiratory failure, acute renal failure, and major cardiovascular events (acute myocardial infarction, congestive heart failure, and cardiac arrhythmias)
  • Acute Renal Failure [Time Frame: During hospitalization, average 5 days] [Designated as safety issue: No]Acute renal failure is defined as a clinical diagnosis of acute renal failure with documented new-onset abnormal renal function (increment > 0.5 mg/dL from baseline).
  • Hospital mortality [Time Frame: During hospitalization, average 5 days] [Designated as safety issue: No]Hospital mortality. Mortality is defined as death occurring during admission.

Descriptive Information[ + expand ][ + ]

Brief TitleSitagliptin Therapy in Hospitalized Patients With Type 2 Diabetes
Official TitleRandomized Controlled Trial on the Safety and Efficacy of Sitagliptin Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes
Brief Summary
High blood glucose levels in hospitalized patients with diabetes are associated with
increased risk of medical complications and death. Improved glucose control with insulin
injections may improve clinical outcome and prevent some of the hospital complications.
Glargine (Lantus®) insulin injection is the most common treatment of diabetes in the
hospital. Sitagliptin (Januvia®)is effective in lowering blood glucose. In a recent pilot
study aiming to determine differences in glycemic control between treatment with sitagliptin
(Januvia®) alone or in combination with basal insulin and basal bolus regimen in general
medicine and surgery patients with type 2 diabetes (T2D). The investigators found that
treatment with sitagliptin alone or in combination with basal insulin resulted in similar
glycemic control compared to basal bolus regimen.

The investigators will conduct a prospective RCT aimed to determine the safety and efficacy
of sitagliptin therapy for in-hospital and post-discharge management of general medicine and
surgical patients with T2D. A total of 280 patients with known history of diabetes will be
randomized to receive sitagliptin plus basal (glargine) insulin once daily (group 1), or
basal bolus regimen with glargine once daily and aspart or lispro insulin before meals
(group 2). If needed, patients in the treatment groups will receive correction doses of
rapid-acting insulin in the presence of hyperglycemia (BG > 140 mg/dl). The overall
hypothesis is that treatment with sitagliptin in combination with basal insulin in patients
with type 2 diabetes will result in a similar improvement in hospital and post-discharge
glycemic control and in a lower frequency of hypoglycemic events than treatment with basal
bolus insulin regimen with glargine once daily and lispro insulin before meals.

Patients will be recruited at Grady Memorial Hospital, Emory University Hospital, University
of Michigan, Ohio State University and Florida Hospital Diabetes institute
Detailed Description
Specific Aim 1: To determine whether in-hospital glycemic control, as measured by mean daily
blood glucose concentration and frequency of hypoglycemic events, is different between
treatment with sitagliptin (Januvia®) in combination with basal insulin (glargine) and basal
bolus regimen (glargine and rapid-acting insulin analog) in general medicine and surgery
patients with T2D. Patients with T2D treated with diet and/or OAD or with low total daily
dose insulin therapy (≤0.4 unit/kg/day) will be randomized to receive sitagliptin plus
glargine insulin (group 1) or basal bolus regimen with glargine once daily and rapid-acting
insulin (lispro or aspart) before meals (group 2). If needed, patients in the 2 treatment
groups will receive supplemental (correction) doses of rapid-acting insulin before meals for
BG > 140 mg/dl.

Specific Aim 2: To determine the efficacy and safety of an A1C based discharge algorithm in
controlling BG after discharge in patients with T2D. Patients who participate in the
in-hospital (Aim 1) arm will be invited to enroll in this open label prospective outpatient
study. The total duration of the study is 6 months. Patients with HbA1c ≤ 7% will be
discharged on the combination of metformin and sitagliptin (Janumet ®) twice daily. Those
with HbA1c between 7% and 9% will be discharged on metformin and sitagliptin (Janumet ®)
twice daily plus glargine insulin at 50% of the inpatient glargine dose. Those with HbA1c >
9% will be discharged on metformin and sitagliptin (Janumet ®) twice-daily plus glargine
insulin at 80% of the inpatient dose.
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionType 2 Diabetes
InterventionDrug: Sitagliptin + glargine
Sitagliptin and Glargine once daily + correction doses of rapid acting insulin if needed
Other Names:
Januvia and LantusDrug: Basal Bolus
Basal bolus regimen with glargine once daily and rapid-acting insulin (lispro or aspart) before meals + + correction doses of rapid acting insulin if needed
Other Names:
Glargine (Lantus) + aspart (Novolog) or lispro (Humalog)Drug: Metformin and sitagliptin
Patients with HbA1c ≤ 7% will be discharged on the combination of metformin and sitagliptin (Janumet ® 500/50 mg) twice daily for 6 months
Other Names:
JanumetDrug: Metformin and sitagliptin + glargine 50%
Patients with HbA1c between 7% and 9% will be discharged on metformin and sitagliptin (Janumet ® 500/50 mg) twice daily plus glargine insulin (50% of the inpatient glargine dose) for 6 months
Other Names:
Janumet, LantusDrug: Metformin and sitagliptin + glargine 80%
Patients with HbA1c > 9% will be discharged on metformin and sitagliptin (Janumet ® 500/50 mg) twice daily plus glargine insulin (80% of the inpatient glargine dose) for 6 months
Other Names:
Janumet, Lantus
Study Arm (s)
  • Experimental: Sitagliptin + glargine (Hospital)
    Sitagliptin and glargine once daily + correction doses of aspart or lispro if needed
  • Active Comparator: Basal bolus (Hospital)
    Glargine once daily and rapid-acting insulin before meals + correction doses of aspart or lispro if needed
  • Experimental: Metformin and Sitagliptin
    Patients with HbA1c ≤ 7% will be discharged on the combination of metformin and sitagliptin (Janumet ® 500/50 mg) twice daily for 6 months
  • Experimental: Metformin and sitagliptin + glargine 50%
    Patients with HbA1c between 7% and 9% will be discharged on metformin and sitagliptin (Janumet ® 500/50 mg) twice daily plus glargine insulin (50% of the inpatient glargine dose) for 6 months
  • Experimental: Metformin and sitagliptin + glargine 80%
    Patients with HbA1c > 9% will be discharged on metformin and sitagliptin (Janumet ® 500/50 mg) twice daily plus glargine insulin (80% of the inpatient glargine dose) for 6 months

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment280
Estimated Completion DateDecember 2016
Estimated Primary Completion DateDecember 2015
Eligibility Criteria
Inclusion Criteria:

1. Males or females between the ages of 18 and 80 years admitted to medicine and surgery
services.

2. A known history of T2D > 3 months, receiving either diet alone, oral antidiabetic
agents: sulfonylureas and metformin as monotherapy or in combination therapy
(excluding DPP-4 inhibitors) or low-dose (≤ 0.4 units/kg/day) insulin therapy.

3. Subjects with a BG >140 mg and < 400 mg/dL without laboratory evidence of diabetic
ketoacidosis (serum bicarbonate < 18 mEq/L or positive serum or urinary ketones).

Exclusion Criteria:

1. Age < 18 or > 80 years.

2. Subjects with increased BG concentration, but without a history of diabetes (stress
hyperglycemia).

3. Subjects with a history of type 1 diabetes (suggested by BMI < 25 requiring insulin
therapy or with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic
state, or ketonuria) [46].

4. Treatment with DPP4 inhibitor or Glucagon like peptide 1 (GLP1) analogs during the
past 3 months prior to admission.

5. Acute critical illness or coronary artery bypass graft (CABG) surgery expected to
require admission to a critical care unit.

6. Subjects with gastrointestinal obstruction or adynamic ileus or those expected to
require gastrointestinal suction.

7. Medical or surgical patients expected to be kept NPO for >24-48 hours after admission
or after completion of surgical procedure.

8. Patients with clinically relevant pancreatic or gallbladder disease.

9. Patients with acute myocardial infarction, clinically significant hepatic disease or
significantly impaired renal function (serum creatinine ≥ 2.0 mg/dL or GFR < 30
ml/min).

10. Treatment with oral or injectable corticosteroid.

11. Mental condition rendering the subject unable to understand the nature, scope, and
possible consequences of the study.

12. Female subjects are pregnant or breast feeding at time of enrollment into the study.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Guillermo E Umpierrez, MD
404-778-1665
geumpie@emory.edu
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01845831
Other Study ID NumbersIRB00063642
Has Data Monitoring CommitteeYes
Information Provided ByEmory University
Study SponsorEmory University
CollaboratorsNot Provided
Investigators Principal Investigator: Guillermo Umpierrez, MD Emory University SOM
Verification DateOctober 2013

Locations[ + expand ][ + ]

Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Contact: Guillermo Umpierrez, MD | geumpie@emory.edu
Principal Investigator: Guillermo Umpierrez, MD
Recruiting
Emory University Hospital
Atlanta, Georgia, United States, 30324
Contact: Dawn Smiley, MD | dsmiley@emory.edu
Sub-Investigator: Dawn Smiley, MD
Recruiting
University of Michigan
Ann Arbor, Michigan, United States, 48109
Contact: Roma Gianchandani, MD | romag@med.umich.edu
Principal Investigator: Roma Gianchandani, MD
Recruiting
Ohio State University
Columbus, Ohio, United States, 43210
Contact: Kathleen Dungan, MD | Kathleen.Dungan@osumc.edu
Principal Investigator: Kathleen Dungan, MD
Recruiting
Temple University
Philadelphia, Pennsylvania, United States, 19140
Contact: Daniel Rubin, MD | Daniel.Rubin@tuhs.temple.edu
Principal Investigator: Daniel Rubin, MD
Not yet recruiting