Trial Outcomes & Findings for Ertugliflozin vs. Glimepiride in Type 2 Diabetes Mellitus (T2DM) Participants on Metformin (MK-8835-002) (NCT NCT01999218)

NCT ID: NCT01999218

Last Updated: 2019-04-02

Results Overview

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). A1C represents the percentage of glycated hemoglobin. This change from baseline reflects the Week 52 A1C minus the Week 0 A1C. A negative number indicates a reduction in A1C level. Participants who met glycemic rescue criteria received open-label sitagliptin glycemic rescue medication. The primary study objective was the MK-8835 15 mg vs. glimepiride comparison; the MK-8835 5mg vs glimerpiride comparison was a secondary study objective.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1326 participants

Primary outcome timeframe

Baseline and Week 52

Results posted on

2019-04-02

Participant Flow

The trial was conducted in 16 countries at 232 trial centers in Argentina, Canada, Czech Republic, Hungary, South Korea, Lithuania, Mexico, Philippines, Poland, Romania, Russia, Slovakia, South Africa, Taiwan, Ukraine, and the United States.

A total of 1326 participants were randomized. Ten randomized participants from one trial site were excluded from all final analyses (Week 104 and beyond), and one randomized participant did not receive treatment.

Participant milestones

Participant milestones
Measure	Ertugliflozin 5 mg Ertugliflozin 5 mg once daily (QD) from Day 1 to Week 104	Ertugliflozin 15 mg Ertugliflozin 15 mg QD from Day 1 to Week 104	Glimepiride Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104
Overall Study STARTED	448	441	437
Overall Study Treated	448	440	437
Overall Study Site Issue	445	435	435
Overall Study COMPLETED	339	340	327
Overall Study NOT COMPLETED	109	101	110

Reasons for withdrawal

Reasons for withdrawal
Measure	Ertugliflozin 5 mg Ertugliflozin 5 mg once daily (QD) from Day 1 to Week 104	Ertugliflozin 15 mg Ertugliflozin 15 mg QD from Day 1 to Week 104	Glimepiride Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104
Overall Study Hyperglycemia	18	17	17
Overall Study Lack of Efficacy	1	0	1
Overall Study Lost to Follow-up	22	17	18
Overall Study Non-Compliance With Study Drug	6	4	1
Overall Study Physician Decision	1	4	6
Overall Study Protocol Violation	4	5	4
Overall Study Screen failure	0	1	0
Overall Study Study Terminated By Sponsor	7	5	12
Overall Study Participant moves	2	5	3
Overall Study Withdrawal by Subject	28	29	34
Overall Study Creatinine/eGFR	0	0	1
Overall Study Death	7	1	2
Overall Study Excluded Medication	1	1	2
Overall Study Adverse Event	9	7	7
Overall Study Treated but excluded at 1 trial site	3	5	2

Baseline Characteristics

All randomized participants

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline and Week 52

Population: All randomized, treated participants with at least one A1C measurement (baseline or a post-baseline).

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=448 Participants Ertugliflozin 5 mg once daily (QD) from Day 1 to Week 104	Ertugliflozin 15 mg n=440 Participants Ertugliflozin 15 mg QD from Day 1 to Week 104	Glimepiride n=437 Participants Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104
Change From Baseline in Hemoglobin A1C (A1C) at Week 52: Excluding Rescue Approach	-0.56 Percent Interval -0.65 to -0.47	-0.64 Percent Interval -0.73 to -0.55	-0.74 Percent Interval -0.83 to -0.65

PRIMARY outcome

Timeframe: Up to Week 106

Population: All randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=445 Participants Ertugliflozin 5 mg once daily (QD) from Day 1 to Week 104	Ertugliflozin 15 mg n=435 Participants Ertugliflozin 15 mg QD from Day 1 to Week 104	Glimepiride n=435 Participants Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104
Percentage of Participants Experiencing An Adverse Event (AE) Up to Week 106	70.1 Percentage of Participants	71.3 Percentage of Participants	69.7 Percentage of Participants

PRIMARY outcome

Timeframe: Up to Week 104

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=445 Participants Ertugliflozin 5 mg once daily (QD) from Day 1 to Week 104	Ertugliflozin 15 mg n=435 Participants Ertugliflozin 15 mg QD from Day 1 to Week 104	Glimepiride n=435 Participants Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104
Percentage of Participants Discontinuing Study Treatment Due to an AE Up to Week 104	6.5 Percentage of Participants	8.0 Percentage of Participants	5.1 Percentage of Participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: All randomized participants who took at least one dose of trial treatment.

Symptomatic hypoglycemia was an event with clinical symptoms reported by the investigator as hypoglycemia (biochemical documentation not required). Participants who met glycemic rescue criteria received open-label sitagliptin glycemic rescue medication.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=448 Participants Ertugliflozin 5 mg once daily (QD) from Day 1 to Week 104	Ertugliflozin 15 mg n=440 Participants Ertugliflozin 15 mg QD from Day 1 to Week 104	Glimepiride n=437 Participants Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104
Percentage of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 52: Excluding Rescue Approach	3.1 Percentage of Participants	5.2 Percentage of Participants	19.2 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: All randomized, treated participants with at least one body weight measurement (baseline or a post-baseline).

This change from baseline reflects the Week 52 body weight minus the Week 0 body weight. Participants who met glycemic rescue criteria received open-label sitagliptin glycemic rescue medication.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=448 Participants Ertugliflozin 5 mg once daily (QD) from Day 1 to Week 104	Ertugliflozin 15 mg n=440 Participants Ertugliflozin 15 mg QD from Day 1 to Week 104	Glimepiride n=437 Participants Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104
Change From Baseline in Body Weight at Week 52 Excluding Rescue Approach	-2.96 Kilograms Interval -3.31 to -2.61	-3.38 Kilograms Interval -3.73 to -3.03	0.91 Kilograms Interval 0.56 to 1.25

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: All randomized, treated participants with at least one SBP measurement (baseline or a post-baseline).

This change from baseline reflects the Week 52 SBP minus the Week 0 SBP. Participants who met glycemic rescue criteria received open-label sitagliptin glycemic rescue medication.

Outcome measures

Outcome measures
Measure	Ertugliflozin 5 mg n=448 Participants Ertugliflozin 5 mg once daily (QD) from Day 1 to Week 104	Ertugliflozin 15 mg n=440 Participants Ertugliflozin 15 mg QD from Day 1 to Week 104	Glimepiride n=437 Participants Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104
Change From Baseline in Sitting Systolic Blood Pressure (SBP) at Week 52 Excluding Rescue Approach	-2.25 mmHg Interval -3.36 to -1.13	-3.81 mmHg Interval -4.91 to -2.71	0.95 mmHg Interval -0.15 to 2.06

Adverse Events

Ertugliflozin 5 mg

Serious events: 41 serious events

Other events: 110 other events

Deaths: 7 deaths

Ertugliflozin 15 mg

Serious events: 32 serious events

Other events: 104 other events

Deaths: 2 deaths

Glimepiride

Serious events: 30 serious events

Other events: 165 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Ertugliflozin 5 mg n=445 participants at risk Ertugliflozin 5 mg once daily (QD) from Day 1 to Week 104	Ertugliflozin 15 mg n=435 participants at risk Ertugliflozin 15 mg QD from Day 1 to Week 104	Glimepiride n=435 participants at risk Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104
Gastrointestinal disorders Diarrhoea	2.9% 13/445 • Number of events 17 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	2.8% 12/435 • Number of events 12 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	5.1% 22/435 • Number of events 24 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.
Infections and infestations Common cold	4.7% 21/445 • Number of events 31 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	3.9% 17/435 • Number of events 29 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	5.3% 23/435 • Number of events 31 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.
Infections and infestations Upper respiratory tract infection	6.1% 27/445 • Number of events 39 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	3.2% 14/435 • Number of events 19 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	4.1% 18/435 • Number of events 27 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.
Infections and infestations Urinary tract infection	6.1% 27/445 • Number of events 30 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	6.4% 28/435 • Number of events 33 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	6.7% 29/435 • Number of events 36 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.
Metabolism and nutrition disorders Asymptomatic hypoglycaemia	1.6% 7/445 • Number of events 11 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	0.92% 4/435 • Number of events 5 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	6.2% 27/435 • Number of events 87 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.
Metabolism and nutrition disorders Hypoglycaemia	3.1% 14/445 • Number of events 31 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	5.7% 25/435 • Number of events 53 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	18.9% 82/435 • Number of events 470 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.
Nervous system disorders Headache	5.6% 25/445 • Number of events 27 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	4.4% 19/435 • Number of events 22 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.	4.4% 19/435 • Number of events 20 • Up to Week 106 The safety analysis population included all randomized participants who took at least one dose of trial treatment, 10 randomized participants from one trial site were excluded from these analyzes, and one randomized participant did not receive treatment.

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 The sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ertugliflozin 5 mg n=448 Participants Ertugliflozin 5 mg once daily (QD) from Day 1 to Week 104	Ertugliflozin 15 mg n=441 Participants Ertugliflozin 15 mg QD from Day 1 to Week 104	Glimepiride n=437 Participants Glimepiride to a maximum of 8 mg QD from Day 1 to Week 104	Total n=1326 Participants Total of all reporting groups
Age, Continuous	58.8 Years STANDARD_DEVIATION 9.7 • n=448 Participants • All randomized participants	58.0 Years STANDARD_DEVIATION 9.9 • n=441 Participants • All randomized participants	57.8 Years STANDARD_DEVIATION 9.2 • n=437 Participants • All randomized participants	58.2 Years STANDARD_DEVIATION 9.6 • n=1326 Participants • All randomized participants
Sex: Female, Male Female	221 Participants n=448 Participants	250 Participants n=441 Participants	213 Participants n=437 Participants	684 Participants n=1326 Participants
Sex: Female, Male Male	227 Participants n=448 Participants	191 Participants n=441 Participants	224 Participants n=437 Participants	642 Participants n=1326 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=448 Participants • All randomized participants	3 Participants n=441 Participants • All randomized participants	5 Participants n=437 Participants • All randomized participants	13 Participants n=1326 Participants • All randomized participants
Race (NIH/OMB) Asian	81 Participants n=448 Participants • All randomized participants	86 Participants n=441 Participants • All randomized participants	73 Participants n=437 Participants • All randomized participants	240 Participants n=1326 Participants • All randomized participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=448 Participants • All randomized participants	0 Participants n=441 Participants • All randomized participants	0 Participants n=437 Participants • All randomized participants	0 Participants n=1326 Participants • All randomized participants
Race (NIH/OMB) Black or African American	17 Participants n=448 Participants • All randomized participants	19 Participants n=441 Participants • All randomized participants	25 Participants n=437 Participants • All randomized participants	61 Participants n=1326 Participants • All randomized participants
Race (NIH/OMB) White	332 Participants n=448 Participants • All randomized participants	316 Participants n=441 Participants • All randomized participants	318 Participants n=437 Participants • All randomized participants	966 Participants n=1326 Participants • All randomized participants
Race (NIH/OMB) More than one race	13 Participants n=448 Participants • All randomized participants	17 Participants n=441 Participants • All randomized participants	16 Participants n=437 Participants • All randomized participants	46 Participants n=1326 Participants • All randomized participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=448 Participants • All randomized participants	0 Participants n=441 Participants • All randomized participants	0 Participants n=437 Participants • All randomized participants	0 Participants n=1326 Participants • All randomized participants
Body Weight	87.9 Kilograms STANDARD_DEVIATION 18.9 • n=448 Participants • All randomized participants and treated participants.	85.6 Kilograms STANDARD_DEVIATION 19.1 • n=440 Participants • All randomized participants and treated participants.	86.8 Kilograms STANDARD_DEVIATION 20.7 • n=437 Participants • All randomized participants and treated participants.	86.8 Kilograms STANDARD_DEVIATION 19.6 • n=1325 Participants • All randomized participants and treated participants.
Hemoglobin A1C	7.81 Percentage STANDARD_DEVIATION 0.60 • n=448 Participants • All randomized participants with a baseline A1C measurement.	7.80 Percentage STANDARD_DEVIATION 0.60 • n=440 Participants • All randomized participants with a baseline A1C measurement.	7.76 Percentage STANDARD_DEVIATION 0.60 • n=437 Participants • All randomized participants with a baseline A1C measurement.	7.79 Percentage STANDARD_DEVIATION 0.60 • n=1325 Participants • All randomized participants with a baseline A1C measurement.
Sitting Systolic Blood Pressure	130.2 Millimeters of mercury STANDARD_DEVIATION 12.8 • n=448 Participants • All randomized participants with baseline sitting systolic blood pressure data.	130.8 Millimeters of mercury STANDARD_DEVIATION 12.4 • n=440 Participants • All randomized participants with baseline sitting systolic blood pressure data.	129.9 Millimeters of mercury STANDARD_DEVIATION 12.0 • n=437 Participants • All randomized participants with baseline sitting systolic blood pressure data.	130.3 Millimeters of mercury STANDARD_DEVIATION 12.4 • n=1325 Participants • All randomized participants with baseline sitting systolic blood pressure data.
Prior Antihyperglycemic (AHA) Medication (Monotherapy or Dual Therapy) Prior Antihyperglycemic Medication	448 Participants n=448 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use	439 Participants n=441 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use	437 Participants n=437 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use	1324 Participants n=1326 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use
Prior Antihyperglycemic (AHA) Medication (Monotherapy or Dual Therapy) No Prior Use & Not on Antihyperglycemic Medication	0 Participants n=448 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use	1 Participants n=441 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use	0 Participants n=437 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use	1 Participants n=1326 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use
Prior Antihyperglycemic (AHA) Medication (Monotherapy or Dual Therapy) Data not available	0 Participants n=448 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use	1 Participants n=441 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use	0 Participants n=437 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use	1 Participants n=1326 Participants • All randomized participants with information on or baseline data of prior antihyperglycemic medication use
Estimated Glomerular Filtration Rate (eGFR)	88.3 milliliters/minute/1.73 meters^2 STANDARD_DEVIATION 18.7 • n=448 Participants • All randomized and treated participants.	86.7 milliliters/minute/1.73 meters^2 STANDARD_DEVIATION 18.3 • n=440 Participants • All randomized and treated participants.	86.6 milliliters/minute/1.73 meters^2 STANDARD_DEVIATION 18.5 • n=437 Participants • All randomized and treated participants.	87.2 milliliters/minute/1.73 meters^2 STANDARD_DEVIATION 18.5 • n=1325 Participants • All randomized and treated participants.