Trial Outcomes & Findings for Effect of Exenatide, Sitagliptin or Glimepiride on Functional ß -Cell Mass (NCT NCT00775684)

NCT ID: NCT00775684

Last Updated: 2022-06-07

Results Overview

The acute insulin response to arginine (AIRarg) performed during the 340mg/dl glucose clamp allows for estimation of the the beta-cell secretory capacity (AIRmax) or functional beta-cell mass. Changes from baseline to 6 months of AIRmax were compared across groups

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 47 participants
• Primary outcome timeframe: Baseline and 6 months
• Results posted on: 2022-06-07

Participant Flow

Recruitment is now closed for this study. All subject follow-up was completed in the spring of 2012. The purpose of the study was to evaluate three medications for the treatment of high blood sugar.

Participant milestones

Measure	Exenatide Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Sitagliptin Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning	Glimepiride Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl
Overall Study STARTED	17	13	17
Overall Study COMPLETED	14	12	14
Overall Study NOT COMPLETED	3	1	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Exenatide, Sitagliptin or Glimepiride on Functional ß -Cell Mass

Baseline characteristics by cohort

Measure	Exenatide n=17 Participants Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Sitagliptin n=13 Participants Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning	Glimepiride n=17 Participants Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl	Total n=47 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	17 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants	47 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	57 years STANDARD_DEVIATION 2 • n=5 Participants	57 years STANDARD_DEVIATION 3 • n=7 Participants	52 years STANDARD_DEVIATION 3 • n=5 Participants	55.3 years STANDARD_DEVIATION 2.6 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	17 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	30 Participants n=4 Participants
Region of Enrollment United States	17 participants n=5 Participants	13 participants n=7 Participants	17 participants n=5 Participants	47 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: We conducted a randomized controlled trial in 40 adult subjects with early Type 2 diabetes (T2D) who received the glucagon-like peptide (GLP-1) analog exenatide, the dipeptidyl peptidase IV inhibitor sitagliptin or the sulfonylurea glimepiride as an active comparator insulin secretagogue for 6 months.

The acute insulin response to arginine (AIRarg) performed during the 340mg/dl glucose clamp allows for estimation of the the beta-cell secretory capacity (AIRmax) or functional beta-cell mass. Changes from baseline to 6 months of AIRmax were compared across groups

Outcome measures

Measure	Exenatide n=14 Participants Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Sitagliptin n=12 Participants Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning	Glimepiride n=14 Participants Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl
Effect on Functional Beta-cell Mass as Determined by Change in ß-cell Secretory Capacity at 6 Months (μU/ml) Acute Insulin Response (AIRmax)Baseline	214 μU/ml Standard Error 60	149 μU/ml Standard Error 20	133 μU/ml Standard Error 19
Effect on Functional Beta-cell Mass as Determined by Change in ß-cell Secretory Capacity at 6 Months (μU/ml) Acute Insulin Response (AIRmax) 6 Months	188.5 μU/ml Standard Error 34.6	158.3 μU/ml Standard Error 30.3	202.5 μU/ml Standard Error 35.1

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: We conducted a randomized controlled trial in 40 adult subjects with early Type 2 diabetes (T2D) who received the glucagon-like peptide (GLP-1) analog exenatide, the dipeptidyl peptidase IV inhibitor sitagliptin or the sulfonylurea glimepiride as an active comparator insulin secretagogue for 6 months.

AGRmin is performed during the 340mg/dl glucose clamp allows for estimation of the minimum alpha-cell glucagon secretion. Changes from baseline to 6 months of AGRmin were compared across groups.

Outcome measures

Measure	Exenatide n=14 Participants Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Sitagliptin n=12 Participants Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning	Glimepiride n=14 Participants Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl
Effect on Functional Beta-cell Mass as Determined by Change in ß-cell Secretory Capacity at 6 Months (pg/mL) Acute Glucose Response (AGRmin) 6 Months	52 pg/mL Standard Error 12	59 pg/mL Standard Error 19	59 pg/mL Standard Error 8
Effect on Functional Beta-cell Mass as Determined by Change in ß-cell Secretory Capacity at 6 Months (pg/mL) Acute Glucose Response (AGRmin) Baseline	51 pg/mL Standard Error 12	55 pg/mL Standard Error 8	37 pg/mL Standard Error 6

SECONDARY outcome

Timeframe: Baseline and 6 months

The changes in B-cell insulin secretion, Acute Insulin Response to arginine (AIRarg) after 6 months were compared to baseline AIRarg for each group. Listed below are AIRarg at baseline and 6 months for each group.

Outcome measures

Measure	Exenatide n=14 Participants Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Sitagliptin n=12 Participants Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning	Glimepiride n=14 Participants Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl
Change in Acute Insulin Response to Arginine. (AIRarg) Acute Insulin Response (AIRarg) Baseline	52 uU/mL Standard Error 14	35 uU/mL Standard Error 4	44 uU/mL Standard Error 6
Change in Acute Insulin Response to Arginine. (AIRarg) Acute Insulin Response (AIRarg) 6 Months	52 uU/mL Standard Error 11	34 uU/mL Standard Error 6	42 uU/mL Standard Error 4

SECONDARY outcome

Timeframe: Baseline and 6 months

Insulin sensitivity (M/I) was determined by dividing the mean glucose infusion rate required during the 230 mg/dL glucose clamp (M) by the mean prestimulus insulin level (I) between 40 and 45 min of the glucose infusion The mean difference after 6 months in insulin sensitivity (M/I) were compared

Outcome measures

Measure	Exenatide n=14 Participants Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Sitagliptin n=12 Participants Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning	Glimepiride n=14 Participants Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl
Insulin Sensitivity at Baseline and 6 Months M/I Baseline	0.3 ((mg/kg) /min) /uU/mL Standard Error 0.1	0.3 ((mg/kg) /min) /uU/mL Standard Error 0.0	0.3 ((mg/kg) /min) /uU/mL Standard Error 0.1
Insulin Sensitivity at Baseline and 6 Months M/I 6 Months	0.3 ((mg/kg) /min) /uU/mL Standard Error 0.1	0.3 ((mg/kg) /min) /uU/mL Standard Error 0.1	0.3 ((mg/kg) /min) /uU/mL Standard Error 0.1

SECONDARY outcome

Timeframe: Baseline and 6 months

Between ∼60 and 250 mg/dL, the magnitude of AIRarg is a linear function of the plasma glucose level, so the difference in AIRarg at fasting and 230 mg/dL glucose levels divided by the difference in plasma glucose (ΔAIRarg/ΔPG) gives the glucose-potentiation slope (GPS) (8,24-26). Using the y-intercept (b) from the line created by these two points, the plasma glucose level at which half-maximal insulin secretion is achieved (PG50) is derived from solving the equation 1/2 (AIRmax) = (GPS · PG50) + b, and provides a measure of β-cell sensitivity to glucose The mean difference after 6 months in PG 50 were compared. Listed below are the PG50 values at baseline and 6 months.

Outcome measures

Measure	Exenatide n=14 Participants Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects Exenatide: Exenatide (Byetta®)-5 µg injected subcutaneously twice daily and increased after 1 month to 10 µg twice daily as tolerated by gastrointestinal effects	Sitagliptin n=12 Participants Sitagliptin (Januvia®)-100 mg by mouth every morning Sitagliptin: Sitagliptin (Januvia®)100 mg by mouth every morning	Glimepiride n=14 Participants Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl Glimepiride: Glimepiride (Amaryl®)-0.5 mg by mouth every morning and then increased by 0.5 - 1.0 mg at each monthly visit to achieve an average fasting glucose \< 110mg/dl
PG 50 (the Plasma Glucose Level at Which Half-maximal Insulin Secretion is Achieved During the Glucose-potentiated Arginine Test) at Baseline and 6 Months PG50 Baseline	175 mg/dL Standard Error 13	226 mg/dL Standard Error 12	168 mg/dL Standard Error 17
PG 50 (the Plasma Glucose Level at Which Half-maximal Insulin Secretion is Achieved During the Glucose-potentiated Arginine Test) at Baseline and 6 Months PG50 6 Months	190 mg/dL Standard Error 14	209 mg/dL Standard Error 16	182 mg/dL Standard Error 10

Adverse Events

Exenatide

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sitagliptin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Glimepiride

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Professor of Medicine, Director of Translational Research Program

University of Pennsylvania

Phone: 215 746-0025

Email: rickels@pennmedicine.upenn.edu

Results disclosure agreements

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