Trial Outcomes & Findings for Dipeptidyl Peptidase-4 Inhibitor (Sitagliptin) Therapy in the Inpatients With Type 2 Diabetes (NCT NCT01378117)

NCT ID: NCT01378117

Last Updated: 2018-12-07

Results Overview

The primary outcome of the study is to determine differences in glycemic control as measured by mean BG concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with type 2 diabetes mellitus, at the time of admission to the blood glucose levels 24hrs after the therapy

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 90 participants
• Primary outcome timeframe: Admission and after 1st day of therapy
• Results posted on: 2018-12-07

Participant Flow

90 patients admitted to general medicine and surgery services in 2012 were enrolled in this pilot study. This study was conducted at Grady Memorial Hospital (Atlanta, GA), Emory University Hospital, and University of Michigan Health System.

Patients were included if they had Type 2 Diabetes with a BG 140-400 mg/dL and were treated at home with diet, oral antidiabetics, or low-dose insulin. 8 patients were excluded from further analysis because they received <24 h of insulin treatment, were transferred to the ICU, or received corticosteroid therapy.

Participant milestones

Measure	Sitagliptin + SSI Prn Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine+ SSI Sitagliptin 50-100 mg po once a day and Subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)
Overall Study STARTED	31	30	29
Overall Study COMPLETED	27	29	26
Overall Study NOT COMPLETED	4	1	3

Reasons for withdrawal

Measure	Sitagliptin + SSI Prn Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine+ SSI Sitagliptin 50-100 mg po once a day and Subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)
Overall Study withdrawal	2	1	2
Overall Study discharged before med given	2	0	1

Baseline Characteristics

Dipeptidyl Peptidase-4 Inhibitor (Sitagliptin) Therapy in the Inpatients With Type 2 Diabetes

Baseline characteristics by cohort

Measure	Sitagliptin + SSI Prn n=27 Participants Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 Participants Sitagliptin 50-100 mg po once a day and subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 Participants Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)	Total n=82 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	23 Participants n=7 Participants	22 Participants n=5 Participants	67 Participants n=4 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants
Age, Continuous	59 years STANDARD_DEVIATION 11 • n=5 Participants	58 years STANDARD_DEVIATION 12 • n=7 Participants	57 years STANDARD_DEVIATION 10 • n=5 Participants	58 years STANDARD_DEVIATION 11 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	16 Participants n=7 Participants	8 Participants n=5 Participants	34 Participants n=4 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	13 Participants n=7 Participants	18 Participants n=5 Participants	48 Participants n=4 Participants
Region of Enrollment United States	27 participants n=5 Participants	29 participants n=7 Participants	26 participants n=5 Participants	82 participants n=4 Participants

PRIMARY outcome

Timeframe: Admission and after 1st day of therapy

The primary outcome of the study is to determine differences in glycemic control as measured by mean BG concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with type 2 diabetes mellitus, at the time of admission to the blood glucose levels 24hrs after the therapy

Outcome measures

Measure	Sitagliptin + SSI Prn n=27 Participants Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 Participants Sitagliptin 50-100 mg po once a day and subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 Participants Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)
Mean Blood Glucose Levels Among the Three Groups at the Time of Hospitalization to 1st Day After Therapy At time of admission	209 mg/dl Standard Deviation 67	203 mg/dl Standard Deviation 48	225 mg/dl Standard Deviation 74
Mean Blood Glucose Levels Among the Three Groups at the Time of Hospitalization to 1st Day After Therapy After 1st day of therapy	168.4 mg/dl Standard Deviation 35	154.2 mg/dl Standard Deviation 29	158.3 mg/dl Standard Deviation 31

SECONDARY outcome

Timeframe: during hospitalization,up to 10 days

Hypoglycemia is defined as blood glucose (BG) reading <70 mg/dl. The number of hypoglycemia events during hospitalization are recorded and compared among the different groups. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter

Outcome measures

Measure	Sitagliptin + SSI Prn n=27 Participants Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 Participants Sitagliptin 50-100 mg po once a day and subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 Participants Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)
Number of Patients With Hypoglycemic Events Among the Treatment Groups	1 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: during hospitalization,up to 5 days

severe hypoglycemic episodes are defined as blood glucose levels <40 mg/dl. The number of patients with these events during the 5 days of hospitalization are recorded and compared. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter.

Outcome measures

Measure	Sitagliptin + SSI Prn n=27 Participants Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 Participants Sitagliptin 50-100 mg po once a day and subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 Participants Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)
Number of Patients With Severe Hypoglycemic Episodes Among the 3 Treatment Groups	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: during hospitalization,up to 10 days

Mean daily blood glucose levels are measured to assess the treatment Failures. For study purpose Treatment failure was defined as having three or more consecutive Blood Glucose (BG) readings > 240 mg/dL or a mean daily BG >240 mg/dL after the 1st day of treatment. Number of patients with a mean daily BG > 240 mg/dL after the 1st day of treatment are recorded and compared among the treatment groups. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter.

Outcome measures

Measure	Sitagliptin + SSI Prn n=27 Participants Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 Participants Sitagliptin 50-100 mg po once a day and subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 Participants Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)
Number of Patients With a Mean Daily BG > 240 mg/dL After the 1st Day of Treatment Among the Treatment Groups	3 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: during hospitalization, up to 10 days

The total insulin includes total glargine insulin (units/day) and total lispro insulin (units/day) given to subjects for maintaining blood glucose levels during hospitalization in different groups. The goal of therapy was to maintain a fasting and premeal glucose concentration between 100 and 140 mg/dL. The doses of insulin were adjusted daily according to protocol. The mean amount is calculated among the different groups and compared.

Outcome measures

Measure	Sitagliptin + SSI Prn n=27 Participants Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 Participants Sitagliptin 50-100 mg po once a day and subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 Participants Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)
Mean Total Daily Dose of Insulin in Units/Day Given During Hospitalization Among the Three Groups	11.5 units/day Standard Deviation 7	28.2 units/day Standard Deviation 12	39.8 units/day Standard Deviation 22

SECONDARY outcome

Timeframe: during hospitalization, up to 10 days

The duration of stay in days in the hospital between the three groups is calculated and mean number of days is measured.

Outcome measures

Measure	Sitagliptin + SSI Prn n=27 Participants Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 Participants Sitagliptin 50-100 mg po once a day and subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 Participants Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)
Mean Length of Stay in Days in the Hospital Among Different Groups	6.3 days Standard Deviation 3	6.9 days Standard Deviation 3	6.3 days Standard Deviation 3

SECONDARY outcome

Timeframe: during hospitalization, up to 10 days

Acute renal failure is defined as a clinical diagnosis of acute renal failure with documented new-onset abnormal renal function (serum creatinine > 2.2 mg/dL or an increment > 0.5 mg/dL from baseline). The total daily dose of insulin and sitagliptin will be adjusted as per serum creatinine concentration. The total daily insulin dose will be reduced to 0.3 unit/kg in patients with creatinine >1.7 mg/dl. The dose of sitagliptin will be reduced to 50 mg/day in patients with creatinine clearance between 30-50 ml/min (approximate serum creatinine levels >1.7 and ≤3.0 mg/dl for men and >1.5 and ≤2.5 mg/dl for women).

Outcome measures

Measure	Sitagliptin + SSI Prn n=27 Participants Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 Participants Sitagliptin 50-100 mg po once a day and subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 Participants Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)
Number of Subjects With Acute Renal Failure Among the Three Randomized Groups During Hospitalization	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: during hospitalization, up to 10 days

Mortality is defined as death occurring during admission among the participants. The number of deaths in each assigned group is calculated.

Outcome measures

Measure	Sitagliptin + SSI Prn n=27 Participants Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 Participants Sitagliptin 50-100 mg po once a day and subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 Participants Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)
Number of Deaths Among the Subjects in Different Groups	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: during hospitalization, up to 10 days

The blood glucose within target range is defined as the levels between 70 mg/dL and 140 mg/dL. BG was measured before each meal and at bedtime (or every 6 h if a patient was not eating) using a point-of-care glucose meter (ACCUCHECK; Roche, Indianapolis, IN). In addition, BG was measured at any time if a patient experienced symptoms of hypoglycemia or if requested by the treating physician. the percentage of the readings are calculated and compared

Outcome measures

Measure	Sitagliptin + SSI Prn n=27 Participants Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 Participants Sitagliptin 50-100 mg po once a day and subcutaneous glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 Participants Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blood glucose using sliding scale Insulin (SSI)
Percent of Blood Glucose Readings Within Target Range Between 70 and 140 mg/dL Among the Three Groups After 24 Hrs of Randomized Treatment	36 percentage of blood glucose readings Standard Deviation 30	43 percentage of blood glucose readings Standard Deviation 28	43 percentage of blood glucose readings Standard Deviation 26

Adverse Events

Sitagliptin + SSI Prn

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Sitagliptin and Glargine + SSI

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Glargine and Lispro + SSI

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sitagliptin + SSI Prn n=27 participants at risk Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 participants at risk Sitagliptin 50-100 mg po once a day and SQ glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 participants at risk Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blo0d glucose using sliding scale Insulin (SSI)
General disorders Angioedema	3.7% 1/27 • Number of events 1 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	0.00% 0/29 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	0.00% 0/26 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).

Other adverse events

Measure	Sitagliptin + SSI Prn n=27 participants at risk Sitagliptin once daily plus supplemental doses of lispro if needed.	Sitagliptin and Glargine + SSI n=29 participants at risk Sitagliptin 50-100 mg po once a day and SQ glargine insulin once daily + correctional doses of lispro if needed for elevated blood glucose using sliding scale Insulin (SSI)	Glargine and Lispro + SSI n=26 participants at risk Glargine once daily and lispro before meals + supplemental insulin lispro as needed for elevated blo0d glucose using sliding scale Insulin (SSI)
Endocrine disorders Hypoglycemia	3.7% 1/27 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	6.9% 2/29 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	7.7% 2/26 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).
Endocrine disorders Hyperglycemia	11.1% 3/27 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	3.4% 1/29 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	7.7% 2/26 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).
General disorders Pressure Ulcer/Skin Ulcer	11.1% 3/27 • Number of events 3 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	3.4% 1/29 • Number of events 1 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	3.8% 1/26 • Number of events 1 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).
Renal and urinary disorders Urinary Tract infection	3.7% 1/27 • Number of events 1 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	6.9% 2/29 • Number of events 2 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	7.7% 2/26 • Number of events 2 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/27 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	6.9% 2/29 • Number of events 2 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	3.8% 1/26 • Number of events 1 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).
General disorders Wound infection	3.7% 1/27 • Number of events 1 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	0.00% 0/29 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	0.00% 0/26 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).
General disorders Systematic Infection	0.00% 0/27 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	3.4% 1/29 • Number of events 1 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).	0.00% 0/26 • The time frame includes the number of days the subjects stayed in the hospital, the maximum was up to 10 days. Please note that 8 patients did not receive study medication because they either withdrew or were discharged prior to receiving study medication; thus the number of participants at risk is 90-8=82 (as stated).

Additional Information

Guillermo Umpierrez, MD

EUSOM

Phone: 4047781665

Email: geumpie@emory.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place