Trial Outcomes & Findings for Adding Sitagliptin or Pioglitazone to Type 2 Diabetes Mellitus Insufficiently Controlled With Metformin and Sulfonylurea (NCT NCT01195090)

NCT ID: NCT01195090

Last Updated: 2012-10-10

Results Overview

A1C change from baseline to 24 weeks

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 120 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2012-10-10

Participant Flow

The study was started from 01 OCT 2009 to 27 SEP 2011

we screened 135 patients and 120 patients were randomized in a 1: 1 ratio to one of the treatment groups. reson for excluded: 4 patients: ALT or AST >2.5x ULN 8 patiens : withdraw informed consent 3 patiens: baseline A1C>11%

Participant milestones

Measure	Sitagliptin add sitagliptin100mg/d to pre-study OADs	Pioglitazone add pioglitazone 30mg/d to pre-study OADs
Overall Study STARTED	60	60
Overall Study COMPLETED	54	52
Overall Study NOT COMPLETED	6	8

Reasons for withdrawal

Measure	Sitagliptin add sitagliptin100mg/d to pre-study OADs	Pioglitazone add pioglitazone 30mg/d to pre-study OADs
Overall Study Adverse Event	1	2
Overall Study Lost to Follow-up	2	2
Overall Study Protocol Violation	3	4

Baseline Characteristics

Adding Sitagliptin or Pioglitazone to Type 2 Diabetes Mellitus Insufficiently Controlled With Metformin and Sulfonylurea

Baseline characteristics by cohort

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 Participants add pioglitazone 30mg/d to pre-study OADs	Total n=120 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	42 Participants n=93 Participants	49 Participants n=4 Participants	91 Participants n=27 Participants
Age, Categorical >=65 years	18 Participants n=93 Participants	11 Participants n=4 Participants	29 Participants n=27 Participants
Age Continuous	60.1 years STANDARD_DEVIATION 8.9 • n=93 Participants	58.1 years STANDARD_DEVIATION 8.3 • n=4 Participants	59.1 years STANDARD_DEVIATION 8.6 • n=27 Participants
Sex: Female, Male Female	38 Participants n=93 Participants	37 Participants n=4 Participants	75 Participants n=27 Participants
Sex: Female, Male Male	22 Participants n=93 Participants	23 Participants n=4 Participants	45 Participants n=27 Participants
Region of Enrollment Taiwan	60 participants n=93 Participants	60 participants n=4 Participants	120 participants n=27 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy.

A1C change from baseline to 24 weeks

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Mean Change in Glycosylated Hemoglobin (A1C)	-0.71 percentage of Hb Standard Error 0.12	-0.94 percentage of Hb Standard Error 0.12

PRIMARY outcome

Timeframe: Baseline

Population: baseline Laboratory measurements

baseline A1C

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 Participants add pioglitazone 30mg/d to pre-study OADs
Baseline A1C	8.27 percentage of Hb Standard Deviation 0.86	8.54 percentage of Hb Standard Deviation 0.97

PRIMARY outcome

Timeframe: 24 weeks

Population: The percentages of patient achieving an A1C \<7% at endpoint

The percentages of patient achieving an A1C <7% at endpoint

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
The Percentages of Patient Achieving an A1C <7%	28.3 percentage	28.8 percentage

SECONDARY outcome

Timeframe: 24 weeks

Population: An intent-to-treat (ITT) analysis with last observation carried forward was used to assess efficacy.

fasting serum sugar change from baseline to 24 weeks

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Changes in Fasting Plasma Glucose	-23 mg/dl Standard Error 4.0	-36 mg/dl Standard Error 4.0

SECONDARY outcome

Timeframe: 24 weeks

Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy

fasting high sensitive serum C-reactive protein change from baseline to 24 weeks

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Changes in High Sensitive C-reactive Protein	-0.07 mg/dl Standard Error 0.04	-0.19 mg/dl Standard Error 0.04

SECONDARY outcome

Timeframe: 24 weeks

Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy

HOMA-IR change from baseline to 24 weeks

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Changes in Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR)	-0.00 HOMA-IR score Standard Error 0.35	-1.56 HOMA-IR score Standard Error 0.35

SECONDARY outcome

Timeframe: 24 weeks

Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy

body weight change from baseline to 24 weeks

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Body Weight Change	-0.26 kg Standard Error 0.32	1.34 kg Standard Error 0.32

SECONDARY outcome

Timeframe: 24 weeks

Population: All patients who had taken at least one dose of study medication were included in the safety analysis

percentages of total adverse events

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Percentages of Patients With Total Adverse Events (AE)	43.1 percentage	51.7 percentage

SECONDARY outcome

Timeframe: 24 weeks

Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy.

Total-cholesterol change from baseline to 24 weeks

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Change in Fasting Total-cholesterol	0.6 mg/dl Standard Error 3.9	9.9 mg/dl Standard Error 4.0

SECONDARY outcome

Timeframe: 24 weeks

Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy

LDL-C change from baseline to 24 weeks

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Change in Fasting Low-density Lipoprotein Cholesterol (LDL-C)	-1.2 mg/dl Standard Error 3.7	6.6 mg/dl Standard Error 3.7

SECONDARY outcome

Timeframe: 24 weeks

Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy.

TG change from baseline to 24 weeks

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Change in Fasting Triglycerides(TG)	6.3 mg/dl Standard Error 9.3	-23.9 mg/dl Standard Error 9.4

SECONDARY outcome

Timeframe: 24 weeks

Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy.

HDL-C change from baseline to 24 weeks

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Change in Fasting High-density Lipoprotein Cholesterol(HDL-C)	1.3 mg/dl Standard Error 1.2	6.3 mg/dl Standard Error 1.2

SECONDARY outcome

Timeframe: 24 weeks

Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy

ALT change from baseline to 24 weeks

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Change in Fasting Plasma Alanine-aminotransferase (ALT)	-0.0 IU/L Standard Error 2.4	-4.5 IU/L Standard Error 2.4

SECONDARY outcome

Timeframe: 24 weeks

Population: All patients who had taken at least one dose of study medication were included in the safety analysis

Incidence of mild to moderate hypoglycemia after treatment

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Percentages of Patients With Mild to Moderate Hypoglycemia	10 percentage	8.5 percentage

SECONDARY outcome

Timeframe: 24 weeks

Population: All patients who had taken at least one dose of study medication were included in the safety analysis

proportion of edema after treatment

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Percentages of Patients With Edema	0 percentage	27.1 percentage

SECONDARY outcome

Timeframe: 24 weeks

Population: All patients who had taken at least one dose of study medication were included in the safety analysis

Proportion of Gastrointestinal adverse events after treatment

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Percentages of Patients With Gastrointestinal Adverse Events	20.0 percentge	6.8 percentge

SECONDARY outcome

Timeframe: 24 weeks

Population: All patients who had taken at least one dose of study medication were included in the safety analysis

Proportion of Nasopharyngitis after treatment

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Percentages of Patients With Nasopharyngitis	20.0 percentage	18.6 percentage

SECONDARY outcome

Timeframe: 24 weeks

Population: Proportion of severe ypoglycemia after treatment

Proportion of severe hypoglycemia after treatment

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=59 Participants add pioglitazone 30mg/d to pre-study OADs
Percentages of Patients With Severe Hypoglycemia	0 percentage	0 percentage

SECONDARY outcome

Timeframe: baseline

Population: Baseline fasting plasma glucose

Baseline fasting plasma glucose

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 Participants add pioglitazone 30mg/d to pre-study OADs
Baseline Fasting Plasma Glucose	177 mg/dl Standard Deviation 47	182 mg/dl Standard Deviation 38

SECONDARY outcome

Timeframe: baseline

Population: Baseline high sensitive C-reactive Protein

Baseline high sensitive C-reactive Protein

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 Participants add pioglitazone 30mg/d to pre-study OADs
Baseline High Sensitive C-reactive Protein	0.38 mg/dl Standard Deviation 0.36	0.42 mg/dl Standard Deviation 0.68

SECONDARY outcome

Timeframe: Baseline HOMA-IR

Population: Baseline HOMA-IR

Baseline HOMA-IR

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 Participants add pioglitazone 30mg/d to pre-study OADs
Baseline Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR)	5.6 HOMA-IR score Standard Deviation 3.8	4.8 HOMA-IR score Standard Deviation 3.2

SECONDARY outcome

Timeframe: Baseline

Population: Baseline alanine-aminotransferase

Baseline alanine-aminotransferase

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 Participants add pioglitazone 30mg/d to pre-study OADs
Baseline Alanine-aminotransferase (ALT)	34.2 IU/L Standard Deviation 17.5	28.5 IU/L Standard Deviation 15.5

SECONDARY outcome

Timeframe: Baseline

Population: Baseline body weight

Baseline body weight

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 Participants add pioglitazone 30mg/d to pre-study OADs
Baseline Body Weight	69.4 kg Standard Deviation 13.6	65.4 kg Standard Deviation 10.4

SECONDARY outcome

Timeframe: Baseline

Population: Baseline Total cholesterol

Baseline Total cholesterol

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 Participants add pioglitazone 30mg/d to pre-study OADs
Baseline Total Cholesterol	174 mg/dl Standard Deviation 31	194 mg/dl Standard Deviation 33

SECONDARY outcome

Timeframe: Baseline

Population: Baseline TG

Baseline TG

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 Participants add pioglitazone 30mg/d to pre-study OADs
Baseline Triglyceride (TG)	137 mg/dl Standard Deviation 74	164 mg/dl Standard Deviation 73

SECONDARY outcome

Timeframe: Baseline

Population: Baseline LDL-C

Baseline LDL-C

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 Participants add pioglitazone 30mg/d to pre-study OADs
Baseline Low-density Lipoprotein Cholesterol (LDL-C)	102 mg/dl Standard Deviation 25	111 mg/dl Standard Deviation 31

SECONDARY outcome

Timeframe: Baseline

Population: Baseline HDL-C

Baseline HDL-C

Outcome measures

Measure	Sitagliptin n=60 Participants add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 Participants add pioglitazone 30mg/d to pre-study OADs
Baseline High-density Lipoprotein Cholesterol (HDL-C)	42 mg/dl Standard Deviation 12	43 mg/dl Standard Deviation 12

Adverse Events

Sitagliptin

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Pioglitazone

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Sitagliptin n=60 participants at risk add sitagliptin100mg/d to pre-study OADs	Pioglitazone n=60 participants at risk add pioglitazone 30mg/d to pre-study OADs
General disorders edema	0.00% 0/60 • adverse event was recorded after 12 weeks and 24 weeks treatment or was recorded if adverse event was noted at any time during the study period. All adverse events was recorded after treatment. Symptomatic hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia and severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia in which the patient required the assistance of another person.	26.7% 16/60 • Number of events 16 • adverse event was recorded after 12 weeks and 24 weeks treatment or was recorded if adverse event was noted at any time during the study period. All adverse events was recorded after treatment. Symptomatic hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia and severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia in which the patient required the assistance of another person.
General disorders Hypoglycemia	10.0% 6/60 • Number of events 6 • adverse event was recorded after 12 weeks and 24 weeks treatment or was recorded if adverse event was noted at any time during the study period. All adverse events was recorded after treatment. Symptomatic hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia and severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia in which the patient required the assistance of another person.	8.3% 5/60 • Number of events 5 • adverse event was recorded after 12 weeks and 24 weeks treatment or was recorded if adverse event was noted at any time during the study period. All adverse events was recorded after treatment. Symptomatic hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia and severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia in which the patient required the assistance of another person.
Gastrointestinal disorders Gastrointestinal adverse event	20.0% 12/60 • Number of events 12 • adverse event was recorded after 12 weeks and 24 weeks treatment or was recorded if adverse event was noted at any time during the study period. All adverse events was recorded after treatment. Symptomatic hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia and severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia in which the patient required the assistance of another person.	6.7% 4/60 • Number of events 4 • adverse event was recorded after 12 weeks and 24 weeks treatment or was recorded if adverse event was noted at any time during the study period. All adverse events was recorded after treatment. Symptomatic hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia and severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia in which the patient required the assistance of another person.
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	20.0% 12/60 • Number of events 12 • adverse event was recorded after 12 weeks and 24 weeks treatment or was recorded if adverse event was noted at any time during the study period. All adverse events was recorded after treatment. Symptomatic hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia and severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia in which the patient required the assistance of another person.	18.3% 11/60 • Number of events 11 • adverse event was recorded after 12 weeks and 24 weeks treatment or was recorded if adverse event was noted at any time during the study period. All adverse events was recorded after treatment. Symptomatic hypoglycemia was defined as an event with clinical symptoms consistent with hypoglycemia and severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia in which the patient required the assistance of another person.

Additional Information

Dr. Sung-Chen Liu

Department of Internal Medicine, Mackay Memorial Hospital

Phone: 886-2-2543-3535

Email: pine3.tw@yahoo.com.tw

Results disclosure agreements

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