Trial Outcomes & Findings for Beta-Cell Function and Sitagliptin Trial (BEST) (NCT NCT00420511)

Results Overview

Area-under-the-C-peptide-curve (AUCCpep) and area-under-the-glucose-curve (AUCgluc) from 0 to 240 minutes during meal tests were calculated using the trapezoidal rule. Insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Beta-cell function was assessed using the ratio of total AUCCpep to AUCgluc divided by HOMA-IR (AUCCpep/gluc/HOMA-IR), a measure of insulin secretion in the context of ambient insulin sensitivity, analogous to the disposition index and adaptation index. Higher AUCCpep/gluc/HOMA-IR is indicative of better beta-cell function.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

48 weeks

Results posted on

2012-01-02

Participant Flow

Participants were recruited from outpatient clinics at the Leadership Sinai Centre for Diabetes between February 2007 and October 2008.

Participants underwent prerandomization phase of 4-8 weeks of intensive insulin therapy (IIT) consisting of basal detemir and premeal insulin aspart. Only participants who achieved fasting glucose \<7.0 mmol/L 1 day after completing IIT were randomized to either sitagliptin 100 mg once daily or matching placebo.

Participant milestones

Participant milestones
Measure	Sitagliptin Sitagliptin 100 mg once daily and metformin 1000 mg twice a day (bid) by mouth po	Placebo Matching placebo once daily and metformin 1000 mg twice a day (bid) by mouth (po)
Overall Study STARTED	10	11
Overall Study COMPLETED	8	10
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin Sitagliptin 100 mg once daily and metformin 1000 mg twice a day (bid) by mouth po	Placebo Matching placebo once daily and metformin 1000 mg twice a day (bid) by mouth (po)
Overall Study Adverse Event	1	1
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Beta-Cell Function and Sitagliptin Trial (BEST)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin n=10 Participants Sitagliptin 100 mg once daily and metformin 1000 mg twice a day (bid) by mouth po	Placebo n=11 Participants Matching placebo once daily and metformin 1000 mg twice a day (bid) by mouth (po)	Total n=21 Participants Total of all reporting groups
Age Continuous	61.3 years n=93 Participants	60.8 years n=4 Participants	60.9 years n=27 Participants
Sex: Female, Male Female	4 Participants n=93 Participants	3 Participants n=4 Participants	7 Participants n=27 Participants
Sex: Female, Male Male	6 Participants n=93 Participants	8 Participants n=4 Participants	14 Participants n=27 Participants
Race/Ethnicity, Customized White	4 participants n=93 Participants	9 participants n=4 Participants	13 participants n=27 Participants
Race/Ethnicity, Customized Other	6 participants n=93 Participants	2 participants n=4 Participants	8 participants n=27 Participants
Body Mass Index	34.3 kg/m^2 n=93 Participants	32.7 kg/m^2 n=4 Participants	32.7 kg/m^2 n=27 Participants
Duration of diabetes	2.8 years n=93 Participants	3.5 years n=4 Participants	3.0 years n=27 Participants
HbA1c	6.2 percent glycosylated hemoglobin n=93 Participants	6.1 percent glycosylated hemoglobin n=4 Participants	6.1 percent glycosylated hemoglobin n=27 Participants
Area-Under-The-Curve (C-peptide/glucose) / HOMA-IR	114.8 index of beta-cell function n=93 Participants	126.0 index of beta-cell function n=4 Participants	120.0 index of beta-cell function n=27 Participants

PRIMARY outcome

Timeframe: 48 weeks

Area-under-the-C-peptide-curve (AUCCpep) and area-under-the-glucose-curve (AUCgluc) from 0 to 240 minutes during meal tests were calculated using the trapezoidal rule. Insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Beta-cell function was assessed using the ratio of total AUCCpep to AUCgluc divided by HOMA-IR (AUCCpep/gluc/HOMA-IR), a measure of insulin secretion in the context of ambient insulin sensitivity, analogous to the disposition index and adaptation index. Higher AUCCpep/gluc/HOMA-IR is indicative of better beta-cell function.

Outcome measures

Outcome measures
Measure	Sitagliptin n=10 Participants Sitagliptin 100 mg once daily and metformin 1000 mg twice a day (orally administered)	Placebo n=11 Participants Matching placebo once daily and metformin 1000 mg twice a day (orally administered)
Preservation of Beta-cell Function Measured by Area-under-the-curve (C-peptide/Glucose)/HOMA-IR	80.4 index of beta-cell function Interval 52.5 to 205.6	71.2 index of beta-cell function Interval 40.3 to 139.8

SECONDARY outcome

Timeframe: 48 weeks

Insulinogenic index was calculated as the incremental change in insulin from 0 to 30 minutes divided by the incremental change in glucose over the same period of time. Insulinogenic index divided by HOMA-IR provides an additional measure of beta-cell function. A higher value indicates better beta-cell function

Outcome measures

Outcome measures
Measure	Sitagliptin n=10 Participants Sitagliptin 100 mg once daily and metformin 1000 mg twice a day (orally administered)	Placebo n=11 Participants Matching placebo once daily and metformin 1000 mg twice a day (orally administered)
Insulinogenic Index Divided by HOMA-IR at 48 Weeks	3.9 index of beta-cell function Interval 1.9 to 4.9	1.8 index of beta-cell function Interval 1.3 to 2.8

SECONDARY outcome

Timeframe: 48 weeks

Outcome measures

Outcome measures
Measure	Sitagliptin n=10 Participants Sitagliptin 100 mg once daily and metformin 1000 mg twice a day (orally administered)	Placebo n=11 Participants Matching placebo once daily and metformin 1000 mg twice a day (orally administered)
Fasting Blood Glucose at 48 Weeks	6.9 mmol/l Interval 5.5 to 7.4	6.7 mmol/l Interval 6.0 to 7.9

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Outcome data not reported

Adverse Events

Sitagliptin

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sitagliptin n=10 participants at risk Sitagliptin 100 mg once daily and metformin 1000 mg twice a day (bid) by mouth po	Placebo n=11 participants at risk Matching placebo once daily and metformin 1000 mg twice a day (bid) by mouth (po)
Skin and subcutaneous tissue disorders Generalized rash	0.00% 0/10	9.1% 1/11 • Number of events 1
Renal and urinary disorders Renal tumor	10.0% 1/10 • Number of events 1	0.00% 0/11

Other adverse events

Adverse event data not reported

Additional Information

Dr. Ravi Retnakaran

Leadership Sinai Centre for Diabetes, Mount Sinai Hospital

Phone: 416-586-4800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place