Trial Outcomes & Findings for Pioglitazone Add-on Study in Patients With Type 2 Diabetes Mellitus (NCT NCT00086502)

Last Updated: 2016-02-05

Results Overview

HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

353 participants

Primary outcome timeframe

Baseline and week 24

Results posted on

2016-02-05

Participant Flow

First Patient In: 15-Jul-2004. Last Patient Last Visit: 28-Sep-2005 71 study centers worldwide

Patients ≥18 years of age with type 2 diabetes mellitus and inadequate glycemic control \[hemoglobin A1C (HbA1c) ≥7.0 and ≤10.0%\] who were on a stable dose of pioglitazone (≥30 mg/day) after a variable screening period were eligible to enter the 24-week study.

Participant milestones

Participant milestones
Measure	Sitagliptin 100 mg The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).	Placebo The Placebo group includes data from patients randomized to receive treatment with placebo matching sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).
Overall Study STARTED	175	178
Overall Study COMPLETED	149	158
Overall Study NOT COMPLETED	26	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin 100 mg The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).	Placebo The Placebo group includes data from patients randomized to receive treatment with placebo matching sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).
Overall Study Adverse Event	11	2
Overall Study Lack of Efficacy	0	2
Overall Study Lost to Follow-up	3	1
Overall Study Physician Decision	1	1
Overall Study Pregnancy	0	1
Overall Study Protocol Violation	3	3
Overall Study Withdrawal by Subject	5	6
Overall Study Patient Moved	1	1
Overall Study Protocol Discontinuation Criteria	1	3
Overall Study Patient Accidentally Unblinded	1	0

Baseline Characteristics

Pioglitazone Add-on Study in Patients With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin 100 mg n=175 Participants The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).	Placebo n=178 Participants The Placebo group includes data from patients randomized to receive treatment with placebo matching sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).	Total n=353 Participants Total of all reporting groups
Age, Continuous	55.6 years STANDARD_DEVIATION 10.4 • n=5 Participants	56.9 years STANDARD_DEVIATION 11.1 • n=7 Participants	56.2 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	82 Participants n=5 Participants	75 Participants n=7 Participants	157 Participants n=5 Participants
Sex: Female, Male Male	93 Participants n=5 Participants	103 Participants n=7 Participants	196 Participants n=5 Participants
Race/Ethnicity, Customized White	127 participants n=5 Participants	129 participants n=7 Participants	256 participants n=5 Participants
Race/Ethnicity, Customized Black	11 participants n=5 Participants	12 participants n=7 Participants	23 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	21 participants n=5 Participants	22 participants n=7 Participants	43 participants n=5 Participants
Race/Ethnicity, Customized Asian	10 participants n=5 Participants	5 participants n=7 Participants	15 participants n=5 Participants
Race/Ethnicity, Customized Other	6 participants n=5 Participants	10 participants n=7 Participants	16 participants n=5 Participants
HbA1c (Hemoglobin A1c)	8.1 Percent STANDARD_DEVIATION 0.8 • n=5 Participants	8.0 Percent STANDARD_DEVIATION 0.8 • n=7 Participants	8.0 Percent STANDARD_DEVIATION 0.8 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and week 24

Population: The Full Analysis Set (FAS) included all patients with a baseline value and ≥1 post-baseline value for this outcome. Data following glycemic rescue were treated as missing. For FAS patients with no data at Week 24, the last non-baseline observed measurement was carried forward to Week 24.

HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg n=163 Participants The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).	Placebo n=174 Participants The Placebo group includes data from patients randomized to receive treatment with placebo matching sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).
Change From Baseline in HbA1c (Hemoglobin A1C) at Week 24	-0.85 Percent Interval -0.98 to -0.72	-0.15 Percent Interval -0.28 to -0.03

SECONDARY outcome

Timeframe: Baseline and week 24

Change from baseline at Week 24 is defined as Week 24 minus Week 0.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg n=163 Participants The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).	Placebo n=174 Participants The Placebo group includes data from patients randomized to receive treatment with placebo matching sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).
Change From Baseline in FPG (Fasting Plasma Glucose) at Week 24	-16.7 mg/dL Interval -22.4 to -11.0	1.0 mg/dL Interval -4.3 to 6.3

Adverse Events

Sitagliptin 100 mg

Serious events: 5 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 8 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Sitagliptin 100 mg n=175 participants at risk The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).	Placebo n=178 participants at risk The Placebo group includes data from patients randomized to receive treatment with placebo matching sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).
Infections and infestations Any Infections And Infestations	6.3% 11/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	3.4% 6/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Infections and infestations Upper Respiratory Tract Infection	6.3% 11/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	3.4% 6/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Nervous system disorders Any Nervous System Disorders	5.1% 9/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	3.9% 7/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Nervous system disorders Headache	5.1% 9/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	3.9% 7/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Sitagliptin 100 mg n=175 participants at risk The Sitagliptin 100 mg group includes data from patients randomized to receive treatment with 100 mg oral tablets of sitagliptin once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).	Placebo n=178 participants at risk The Placebo group includes data from patients randomized to receive treatment with placebo matching sitagliptin 100 mg tablet once daily (blinded) in addition to ongoing treatment with open-label pioglitazone 15 mg oral tablets (total daily dose 30 to 45 mg/day).
Gastrointestinal disorders Any Gastrointestinal Disorders	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	1.1% 2/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Gastrointestinal disorders Ileitis	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Gastrointestinal disorders Intestinal Obstruction	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Gastrointestinal disorders Periodontitis	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
General disorders Any General Disorders And Administration Site Conditions	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
General disorders Oedema Peripheral	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Hepatobiliary disorders Any Hepatobiliary Disorders	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Hepatobiliary disorders Cholecystitis	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Immune system disorders Any Immune System Disorders	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Immune system disorders Hypersensitivity	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Injury, poisoning and procedural complications Any Injury, Poisoning And Procedural Complications	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Injury, poisoning and procedural complications Lower Limb Fracture	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Musculoskeletal and connective tissue disorders Any Musculoskeletal And Connective Tissue Disorders	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Musculoskeletal and connective tissue disorders Intervertebral Disc Protrusion	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Any Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps)	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Small Cell Lung Cancer	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Nervous system disorders Any Nervous System Disorders	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Nervous system disorders Dizziness	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Pregnancy, puerperium and perinatal conditions Any Pregnancy, Puerperium And Perinatal Conditions	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Pregnancy, puerperium and perinatal conditions Abortion Spontaneous	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Psychiatric disorders Any Psychiatric Disorders	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Psychiatric disorders Depression	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Psychiatric disorders Suicide Attempt	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Skin and subcutaneous tissue disorders Any Skin And Subcutaneous Tissue Disorders	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Skin and subcutaneous tissue disorders Angioneurotic Oedema	0.57% 1/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.00% 0/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Vascular disorders Any Vascular Disorders	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).
Vascular disorders Atherosclerosis Obliterans	0.00% 0/175 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).	0.56% 1/178 • Week 0 through Week 24. Other (not including serious) adverse experience results represent those events included in the primary safety analysis for this study (i.e., events that occurred prior to the initiation of glycemic rescue therapy).