Trial Outcomes & Findings for Metformin Add-on Study in Patients With Type 2 Diabetes Mellitus (0431-020)(COMPLETED) (NCT NCT00086515)

Last Updated: 2017-05-05

Results Overview

A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

701 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2017-05-05

Participant Flow

Primary therapy Period: 13-Jul-2004 through 02-Feb-2007 (for the 2-year Phase A and B periods); 100 study centers worldwide. (46 sites in the United States, 25 sites in 11 countries in Europe, and 29 sites in 13 countries in the rest of the world).

Patients 18-78 years of age with type 2 diabetes mellitus with inadequate glycemic control (hemoglobin A1C \[A1C\] ≥7% and ≤10%) on stable doses of metformin (≥1500 mg/day) were eligible to enter the 104-week study.

Participant milestones

Participant milestones
Measure	Sitagliptin 100 mg The Sitagliptin 100 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin 100 mg during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin 100 mg and glipizide-matched placebo.	Placebo / Glipizide 5 mg The Placebo/Glipizide 5 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin-matched placebo during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin-matched placebo 100 mg and glipizide 5 mg which was allowed to be uptitrated, in a blinded fashion, to a maximum dose of 15 mg/day.
Phase A (Weeks 0-24) STARTED	464	237
Phase A (Weeks 0-24) COMPLETED	415	192
Phase A (Weeks 0-24) NOT COMPLETED	49	45
Phase A to Phase B Transition Period STARTED	415	192
Phase A to Phase B Transition Period COMPLETED	391	164
Phase A to Phase B Transition Period NOT COMPLETED	24	28
Phase B (Weeks 24-104) STARTED	391	164
Phase B (Weeks 24-104) COMPLETED	201	109
Phase B (Weeks 24-104) NOT COMPLETED	190	55

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin 100 mg The Sitagliptin 100 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin 100 mg during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin 100 mg and glipizide-matched placebo.	Placebo / Glipizide 5 mg The Placebo/Glipizide 5 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin-matched placebo during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin-matched placebo 100 mg and glipizide 5 mg which was allowed to be uptitrated, in a blinded fashion, to a maximum dose of 15 mg/day.
Phase A (Weeks 0-24) Adverse Event	17	9
Phase A (Weeks 0-24) Lack of Efficacy	7	13
Phase A (Weeks 0-24) Lost to Follow-up	4	5
Phase A (Weeks 0-24) Protocol Violation	3	1
Phase A (Weeks 0-24) Withdrawal by Subject	10	10
Phase A (Weeks 0-24) Patient Moved	2	3
Phase A (Weeks 0-24) Protocol-Spec lab discon criteria	4	3
Phase A (Weeks 0-24) Poor compliance	1	0
Phase A (Weeks 0-24) Patient needed prohibited treatment	0	1
Phase A (Weeks 0-24) Personal Circumstance	1	0
Phase A to Phase B Transition Period Adverse Event	2	1
Phase A to Phase B Transition Period Lack of Efficacy	2	2
Phase A to Phase B Transition Period Withdrawal by Subject	1	0
Phase A to Phase B Transition Period Protocol Violation	0	1
Phase A to Phase B Transition Period Patient received Phase A rescue therapy	16	23
Phase A to Phase B Transition Period Protocol-Spec lab discon criteria	1	1
Phase A to Phase B Transition Period Poor compliance	1	0
Phase A to Phase B Transition Period Patient needed prohibited treatment	1	0
Phase B (Weeks 24-104) Adverse Event	16	10
Phase B (Weeks 24-104) Lack of Efficacy	94	19
Phase B (Weeks 24-104) Lost to Follow-up	13	4
Phase B (Weeks 24-104) Physician Decision	3	0
Phase B (Weeks 24-104) Protocol Violation	1	0
Phase B (Weeks 24-104) Withdrawal by Subject	15	5
Phase B (Weeks 24-104) Patient Moved	2	2
Phase B (Weeks 24-104) Protocol-Specific discontinuation	5	3
Phase B (Weeks 24-104) Protocol-Specific lab discon criteria	36	10
Phase B (Weeks 24-104) Patient Died	3	1
Phase B (Weeks 24-104) Patient needed prohibited treatment	0	1
Phase B (Weeks 24-104) Personal Circumstance	1	0
Phase B (Weeks 24-104) Discontinued in error	1	0

Baseline Characteristics

Metformin Add-on Study in Patients With Type 2 Diabetes Mellitus (0431-020)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin 100 mg n=464 Participants The Sitagliptin 100 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin 100 mg during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin 100 mg and glipizide-matched placebo.	Placebo / Glipizide 5 mg n=237 Participants The Placebo/Glipizide 5 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin-matched placebo during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin-matched placebo 100 mg and glipizide 5 mg which was allowed to be uptitrated, in a blinded fashion, to a maximum dose of 15 mg/day.	Total n=701 Participants Total of all reporting groups
Age, Continuous	54.4 years STANDARD_DEVIATION 10.4 • n=5 Participants	54.7 years STANDARD_DEVIATION 9.7 • n=7 Participants	54.5 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	205 Participants n=5 Participants	96 Participants n=7 Participants	301 Participants n=5 Participants
Sex: Female, Male Male	259 Participants n=5 Participants	141 Participants n=7 Participants	400 Participants n=5 Participants
Race/Ethnicity, Customized White	293 participants n=5 Participants	159 participants n=7 Participants	452 participants n=5 Participants
Race/Ethnicity, Customized Black	31 participants n=5 Participants	14 participants n=7 Participants	45 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	72 participants n=5 Participants	28 participants n=7 Participants	100 participants n=5 Participants
Race/Ethnicity, Customized Asian	49 participants n=5 Participants	26 participants n=7 Participants	75 participants n=5 Participants
Race/Ethnicity, Customized Other	19 participants n=5 Participants	10 participants n=7 Participants	29 participants n=5 Participants
Fasting Plasma Glucose (FPG)	170.2 mg/dL STANDARD_DEVIATION 40.2 • n=5 Participants	174.1 mg/dL STANDARD_DEVIATION 42.0 • n=7 Participants	171.5 mg/dL STANDARD_DEVIATION 41.3 • n=5 Participants
Hemoglobin A1C (A1C)	8.0 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.

A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg n=453 Participants The Sitagliptin 100 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin 100 mg during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin 100 mg and glipizide-matched placebo.	Placebo / Glipizide 5 mg n=224 Participants The Placebo/Glipizide 5 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin-matched placebo during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin-matched placebo 100 mg and glipizide 5 mg which was allowed to be uptitrated, in a blinded fashion, to a maximum dose of 15 mg/day.
Change From Baseline in Hemoglobin A1C (A1C) at Week 24	-0.67 Percent Interval -0.77 to -0.57	-0.02 Percent Interval -0.15 to 0.1

SECONDARY outcome

Timeframe: Baseline and Week 24

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

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg n=454 Participants The Sitagliptin 100 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin 100 mg during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin 100 mg and glipizide-matched placebo.	Placebo / Glipizide 5 mg n=226 Participants The Placebo/Glipizide 5 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin-matched placebo during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin-matched placebo 100 mg and glipizide 5 mg which was allowed to be uptitrated, in a blinded fashion, to a maximum dose of 15 mg/day.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	-16.9 mg/dL Interval -21.5 to -12.3	8.5 mg/dL Interval 2.9 to 14.1

SECONDARY outcome

Timeframe: Baseline and Week 24

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

Outcome measures

Outcome measures
Measure	Sitagliptin 100 mg n=387 Participants The Sitagliptin 100 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin 100 mg during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin 100 mg and glipizide-matched placebo.	Placebo / Glipizide 5 mg n=182 Participants The Placebo/Glipizide 5 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin-matched placebo during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin-matched placebo 100 mg and glipizide 5 mg which was allowed to be uptitrated, in a blinded fashion, to a maximum dose of 15 mg/day.
Change From Baseline in 2-hour Post-meal Glucose (PMG) at Week 24	-62.0 mg/dL Interval -70.2 to -53.8	-11.4 mg/dL Interval -21.7 to -1.0

Adverse Events

Sitagliptin 100 mg

Serious events: 54 serious events

Other events: 210 other events

Deaths: 0 deaths

Placebo / Glipizide 5 mg

Serious events: 21 serious events

Other events: 124 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Sitagliptin 100 mg n=464 participants at risk The Sitagliptin 100 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin 100 mg during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin 100 mg and glipizide-matched placebo.	Placebo / Glipizide 5 mg n=237 participants at risk The Placebo/Glipizide 5 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin-matched placebo during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin-matched placebo 100 mg and glipizide 5 mg which was allowed to be uptitrated, in a blinded fashion, to a maximum dose of 15 mg/day.
Gastrointestinal disorders Diarrhoea	6.0% 28/464 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.	4.6% 11/237 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.
Infections and infestations Bronchitis	5.6% 26/464 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.	5.1% 12/237 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.
Infections and infestations Influenza	8.0% 37/464 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.	8.4% 20/237 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.
Infections and infestations Nasopharyngitis	8.8% 41/464 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.	6.8% 16/237 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.
Infections and infestations Upper Respiratory Tract Infection	10.6% 49/464 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.	12.2% 29/237 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.
Infections and infestations Urinary Tract Infection	4.7% 22/464 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.	5.5% 13/237 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.
Investigations Blood Glucose Increased	1.7% 8/464 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.	5.9% 14/237 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.
Metabolism and nutrition disorders Hypoglycaemia	3.7% 17/464 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.	17.3% 41/237 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.
Musculoskeletal and connective tissue disorders Back Pain	7.1% 33/464 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.	8.4% 20/237 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.
Nervous system disorders Headache	4.3% 20/464 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.	5.5% 13/237 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.
Vascular disorders Hypertension	6.2% 29/464 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.	7.6% 18/237 • Weeks 0-104 Patients received rescue medication if they met specific glycemic goals. Serious Adverse Events (SAEs) include events that occurred either before or after receiving rescue medication. Other Adverse Events (AEs) only includes those AEs that occurred prior to a patient receiving rescue medication.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

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