Trial Outcomes & Findings for Durability of Combination Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy in New Onset T2DM (NCT NCT01107717)

NCT ID: NCT01107717

Last Updated: 2024-09-05

Results Overview

subjects will be followed for 3 years and the HbA1c measured at this time to provide the values for each arm as defined for the primary outcome of the study

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 318 participants
• Primary outcome timeframe: at the end of the study (3 years)
• Results posted on: 2024-09-05

Participant Flow

Newly diagnosed T2DM participants

Participant milestones

Measure	Triple Therapy initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed metformin\\pioglitazone\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \< 6.5%	Conventional Therapy sequential addition of metformin, glyburide and basal insulin metformin, glyburide and glargine: subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \< 6.5%
Overall Study STARTED	157	161
Overall Study COMPLETED	103	114
Overall Study NOT COMPLETED	54	47

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Durability of Combination Therapy With Exenatide/Pioglitazone/Metformin vs. Conventional Therapy in New Onset T2DM

Baseline characteristics by cohort

Measure	Triple Therapy n=103 Participants initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed metformin\\pioglitazone\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \< 6.5%	Conventional Therapy n=114 Participants sequential addition of metformin, glyburide and basal insulin metformin, glyburide and glargine: subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \< 6.5%	Total n=217 Participants Total of all reporting groups
Age, Continuous	44 years STANDARD_DEVIATION 1 • n=5 Participants	47 years STANDARD_DEVIATION 1 • n=7 Participants	45.5 years STANDARD_DEVIATION 1 • n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	72 Participants n=7 Participants	124 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	42 Participants n=7 Participants	93 Participants n=5 Participants
Race/Ethnicity, Customized Mexican Americans	73 participants n=5 Participants	75 participants n=7 Participants	148 participants n=5 Participants
Race/Ethnicity, Customized Caucasian	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants
Race/Ethnicity, Customized Other	15 participants n=5 Participants	24 participants n=7 Participants	39 participants n=5 Participants
Region of Enrollment United States	103 participants n=5 Participants	114 participants n=7 Participants	217 participants n=5 Participants
Fasting Plasma Glucose	203 mg/dl STANDARD_DEVIATION 6 • n=5 Participants	200 mg/dl STANDARD_DEVIATION 6 • n=7 Participants	201.5 mg/dl STANDARD_DEVIATION 6 • n=5 Participants
Diabetes Duration at start	4.8 Months STANDARD_DEVIATION 0.5 • n=5 Participants	5.2 Months STANDARD_DEVIATION 0.5 • n=7 Participants	5 Months STANDARD_DEVIATION 0.5 • n=5 Participants
Body Mass Index (BMI)	36.4 kg/m^2 STANDARD_DEVIATION 1.1 • n=5 Participants	36.1 kg/m^2 STANDARD_DEVIATION 1.1 • n=7 Participants	36.25 kg/m^2 STANDARD_DEVIATION 1.1 • n=5 Participants
Baseline HbA1c	9.0 percentage of glycated hemoglobin STANDARD_DEVIATION 0.2 • n=5 Participants	8.8 percentage of glycated hemoglobin STANDARD_DEVIATION 0.2 • n=7 Participants	8.9 percentage of glycated hemoglobin STANDARD_DEVIATION 0.2 • n=5 Participants

PRIMARY outcome

Timeframe: at the end of the study (3 years)

subjects will be followed for 3 years and the HbA1c measured at this time to provide the values for each arm as defined for the primary outcome of the study

Outcome measures

Measure	Triple Therapy n=103 Participants initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed metformin\\pioglitazone\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \< 6.5%	Conventional Therapy n=114 Participants sequential addition of metformin, glyburide and basal insulin metformin, glyburide and glargine: subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \< 6.5%
HbA1c Level	6.9 percentage of glycated hemoglobin Standard Error 0.1	6.4 percentage of glycated hemoglobin Standard Error 0.1

SECONDARY outcome

Timeframe: 3 years

Number of participants with HbA1c>6.5% at 3 years

Outcome measures

Measure	Triple Therapy n=103 Participants initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed metformin\\pioglitazone\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \< 6.5%	Conventional Therapy n=114 Participants sequential addition of metformin, glyburide and basal insulin metformin, glyburide and glargine: subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \< 6.5%
Treatment Failure	33 number of participants	59 number of participants

SECONDARY outcome

Timeframe: during the entire study (3 years)

asymptomatic hypoglycemic events with documented PGC < 60 mg/dl and sympotomatic hypoglycemia

Outcome measures

Measure	Triple Therapy n=103 Participants initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed metformin\\pioglitazone\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \< 6.5%	Conventional Therapy n=114 Participants sequential addition of metformin, glyburide and basal insulin metformin, glyburide and glargine: subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \< 6.5%
Percentage of Patients With Reported Hypoglycemic Events	14 Participants	52 Participants

Adverse Events

Triple Therapy

Serious events: 0 serious events

Other events: 44 other events

Deaths: 0 deaths

Conventional Therapy

Serious events: 0 serious events

Other events: 53 other events

Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Triple Therapy n=103 participants at risk initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed metformin\\pioglitazone\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \< 6.5%	Conventional Therapy n=114 participants at risk sequential addition of metformin, glyburide and basal insulin metformin, glyburide and glargine: subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \< 6.5%
Metabolism and nutrition disorders Hypoglycemia	13.6% 14/103 • Number of events 14 • Adverse events were reported from baseline to study end (3 years) for each participant	45.6% 52/114 • Number of events 52 • Adverse events were reported from baseline to study end (3 years) for each participant
Gastrointestinal disorders Nausea	25.2% 26/103 • Number of events 27 • Adverse events were reported from baseline to study end (3 years) for each participant	0.00% 0/114 • Adverse events were reported from baseline to study end (3 years) for each participant
Blood and lymphatic system disorders Peripheral Edema	4.9% 5/103 • Number of events 5 • Adverse events were reported from baseline to study end (3 years) for each participant	0.88% 1/114 • Number of events 1 • Adverse events were reported from baseline to study end (3 years) for each participant

Additional Information

Muhammad Abdul-Ghani, MD

University of Texas Health Science Center at San Antonio

Phone: 210-557-1157

Email: abdulghani@uthscsa.edu

Results disclosure agreements

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