Trial Outcomes & Findings for A Study of the Safety and Efficacy of MK-1293 Compared to Lantus™ in Participants With Type 1 Diabetes Mellitus (T1DM) (MK-1293-003) (NCT NCT02059161)

NCT ID: NCT02059161

Last Updated: 2018-09-05

Results Overview

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 24 A1C minus the Week 0 A1C.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

508 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2018-09-05

Participant Flow

Participants at least 18 years of age who have had Type 1 diabetes mellitus (T1DM) for at least one year prior to study start.

Participant milestones

Participant milestones
Measure	MK-1293 MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Overall Study STARTED	245	263
Overall Study Treated	241	258
Overall Study COMPLETED	196	222
Overall Study NOT COMPLETED	49	41

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-1293 MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Overall Study Pregnancy	0	2
Overall Study Adverse Event	2	6
Overall Study Lost to Follow-up	20	12
Overall Study Physician Decision	4	4
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	16	13
Overall Study Randomized in error, no study drug	0	1
Overall Study Non-compliance with study drug	6	2

Baseline Characteristics

A Study of the Safety and Efficacy of MK-1293 Compared to Lantus™ in Participants With Type 1 Diabetes Mellitus (T1DM) (MK-1293-003)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-1293 n=245 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=263 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Total n=508 Participants Total of all reporting groups
Age, Continuous	41.8 Years STANDARD_DEVIATION 14.5 • n=5 Participants	41.6 Years STANDARD_DEVIATION 14.8 • n=7 Participants	41.7 Years STANDARD_DEVIATION 14.6 • n=5 Participants
Sex: Female, Male Female	106 Participants n=5 Participants	111 Participants n=7 Participants	217 Participants n=5 Participants
Sex: Female, Male Male	139 Participants n=5 Participants	152 Participants n=7 Participants	291 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Outcome measures

Outcome measures
Measure	MK-1293 n=241 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Primary: Change From Baseline in Hemoglobin A1c (A1C) at Week 24	-0.62 Percent Interval -0.79 to -0.45	-0.66 Percent Interval -0.82 to -0.5

PRIMARY outcome

Timeframe: Up to Week 24

Population: The analysis population included all randomized, treated participants who had data for AIA at or before Week 24.

Percentage of participants with confirmed positive AIA at any time up through Week 24 including baseline.

Outcome measures

Outcome measures
Measure	MK-1293 n=241 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Percentage of Participants With Any Confirmed Positive Anti-insulin Antibody (AIA) at Any Time Up Through Week 24	70.1 Percentage of participants	74.0 Percentage of participants

PRIMARY outcome

Timeframe: Up to Week 24

Population: The analysis population included all randomized, treated participants who were AIA negative at baseline and had data for AIA at or before Week 24.

Percentage of participants who became positive to AIA at or before Week 24, among participants who were AIA negative at baseline.

Outcome measures

Outcome measures
Measure	MK-1293 n=101 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=98 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Percentage of Participants With Negative AIA at Baseline Who Develop Confirmed Positive AIA at Any Time Up Through Week 24	32.7 Percentage of participants	35.7 Percentage of participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: The analysis population included all randomized, treated participants who had AIA data at baseline and Week 24.

This immunogenicity analysis will assess the effect of treatment with MK-1293 compared with Lantus on anti-insulin antibody development after 24 weeks of treatment. This change from baseline reflects the Week 24 AIA titer minus the Week 0 AIA titer.

Outcome measures

Outcome measures
Measure	MK-1293 n=185 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=198 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Change From Baseline in AIA Titer After 24 Weeks of Treatment	0.4 AIA Titers Standard Deviation 15.9	0.3 AIA Titers Standard Deviation 23.2

PRIMARY outcome

Timeframe: Up to Week 24

Population: The analysis population included all randomized, treated participants who were INAb negative at baseline and who had data for INAb at or before Week 24.

Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 24. This immunogenicity analysis assessed the effect of treatment with MK-1293 and with Lantus on insulin-neutralizing antibody (INab) development up through 24 weeks of treatment.

Outcome measures

Outcome measures
Measure	MK-1293 n=232 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=246 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 24	3.9 Percentage of participants	5.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 52 A1C minus the Week 0 A1C.

Outcome measures

Outcome measures
Measure	MK-1293 n=241 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Change From Baseline in A1C at Week 52	-0.35 Percent Interval -0.53 to -0.17	-0.33 Percent Interval -0.5 to -0.16

SECONDARY outcome

Timeframe: Week 24

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).

Outcome measures

Outcome measures
Measure	MK-1293 n=224 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=235 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Total Insulin Dose at Week 24	58.74 Insulin units Interval 53.39 to 64.1	60.51 Insulin units Interval 55.21 to 65.81

SECONDARY outcome

Timeframe: Week 24

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).

Outcome measures

Outcome measures
Measure	MK-1293 n=224 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=235 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Total Insulin Dose Per Kilogram (kg) of Body Weight (Unit/kg) at Week 24	0.75 Insulin units/kg. Interval 0.69 to 0.81	0.77 Insulin units/kg. Interval 0.72 to 0.83

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Blood glucose was measured on a fasting basis (collected after a 10-hour fast). FPG is expressed as mg/dL. This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0.

Outcome measures

Outcome measures
Measure	MK-1293 n=241 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	-16.8 mg/dL Interval -33.4 to -0.2	-26.4 mg/dL Interval -42.5 to -10.3

SECONDARY outcome

Timeframe: Up to Week 52 including baseline

Population: The analysis population included all randomized, treated participants who had data for AIA at or before Week 52.

Percentage of participants with confirmed positive AIA at any time up through Week 52 including baseline.

Outcome measures

Outcome measures
Measure	MK-1293 n=241 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Percentage of Participants With Confirmed Positive AIA Up Through Week 52	73.4 Percentage of participants	75.6 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: The analysis population included all randomized, treated participants who had data for AIA at baseline and Week 52.

Percentage of participants who became positive to AIA at or before Week 52, among participants who were AIA negative at baseline.

Outcome measures

Outcome measures
Measure	MK-1293 n=101 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=98 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Percentage of Participants With Negative AIA at Baseline Who Develop Confirmed Positive AIA at Any Time Up Through Week 52	40.6 Percentage of participants	39.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The analysis population included all randomized, treated participants who had AIA data at baseline and Week 52.

This immunogenicity analysis assessed the effect of treatment with MK-1293 compared with Lantus on anti-insulin antibody development after 52 weeks of treatment. This change from baseline reflects the AIA titers at Week 52 minus the AIA titers at Week 0.

Outcome measures

Outcome measures
Measure	MK-1293 n=164 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=177 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Change From Baseline in AIA Titer After 52 Weeks of Treatment	-1.6 AIA Titers Standard Deviation 9.9	0.1 AIA Titers Standard Deviation 20.3

SECONDARY outcome

Timeframe: Week 52

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).

Outcome measures

Outcome measures
Measure	MK-1293 n=228 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=240 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Total Insulin Dose at Week 52	59.16 Insulin units Interval 53.97 to 64.34	60.93 Insulin units Interval 55.79 to 66.06

SECONDARY outcome

Timeframe: Week 52

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Total insulin dose = basal insulin (MK-1293 or Lantus) + bolus (prandial) insulin (non-study medication).

Outcome measures

Outcome measures
Measure	MK-1293 n=228 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=240 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Total Insulin Dose Per Kilogram (kg) of Body Weight (Unit/kg) at Week 52	0.75 Insulin units/kg. Interval 0.7 to 0.81	0.77 Insulin units/kg. Interval 0.71 to 0.82

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Blood glucose was measured on a fasting basis (collected after a 10-hour fast). This change from baseline reflects the FPG level at Week 52 minus the FPG level at Week 0.

Outcome measures

Outcome measures
Measure	MK-1293 n=241 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Change From Baseline in FPG at Week 52	-17.9 mg/dL Interval -35.8 to 0.1	-12.5 mg/dL Interval -29.9 to 4.9

SECONDARY outcome

Timeframe: Up to Week 52

Population: The analysis population included all randomized, treated participants who were INAb negative at baseline and who had data for INAb at or before Week 52.

Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Thought Week 52. This immunogenicity analysis assessed the effect of treatment with MK-1293 and with Lantus on insulin-neutralizing antibody (INAb) development up through 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	MK-1293 n=232 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=246 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Percentage of Participants Who Develop Insulin Neutralizing Antibodies Up Through Week 52	4.7 Percentage of participants	6.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

The 7-point SMBG profile consisted of the following measurements by glucose meter: morning pre-meal (fasting), 2 hours after morning meal, midday pre-meal, 2 hours after midday meal, evening pre meal, pre-bedtime (pre-dose and at least 2 hours after evening meal), between 2:00 AM and 4:00 AM in the morning.

Outcome measures

Outcome measures
Measure	MK-1293 n=226 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=248 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) at Week 24	-4.9 mg/dL Interval -15.8 to 5.9	-4.6 mg/dL Interval -14.9 to 5.8

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Outcome measures

Outcome measures
Measure	MK-1293 n=229 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=249 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Change From Baseline in 7-point SMBG at Week 52	-12.0 mg/dL Interval -25.8 to 1.7	-4.0 mg/dL Interval -16.3 to 8.4

SECONDARY outcome

Timeframe: 24 weeks

Population: The analysis population included all randomized, treated participants with a Week 24 A1C measurement.

Percentage of participants attaining A1C glycemic goals of \<7.0% and \<6.5% after 24 weeks of treatment.

Outcome measures

Outcome measures
Measure	MK-1293 n=219 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=236 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 24 Weeks of Treatment. A1C < 7.0%	37.0 Percentage of participants	37.7 Percentage of participants
Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 24 Weeks of Treatment. A1C < 6.5%	20.5 Percentage of participants	21.6 Percentage of participants

SECONDARY outcome

Timeframe: 52 weeks

Population: The analysis population included all randomized, treated participants with a Week 52 A1C measurement.

Percentage of participants attaining A1C glycemic goals of \<7.0% and \<6.5% after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	MK-1293 n=197 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=221 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 52 Weeks of Treatment. A1C < 7.0%	31.0 Percentage of participants	30.8 Percentage of participants
Percentage of Participants Attaining A1C Glycemic Goals of <7% and <6.5% After 52 Weeks of Treatment. A1C < 6.5%	14.2 Percentage of participants	18.6 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Basal Insulin Dose at Week 52.

Outcome measures

Outcome measures
Measure	MK-1293 n=241 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Basal Insulin Dose at Week 52	36.08 Units Interval 33.14 to 39.03	36.51 Units Interval 33.63 to 39.39

SECONDARY outcome

Timeframe: Week 52

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Basal Insulin Dose per kg of Body Weight at Week 52.

Outcome measures

Outcome measures
Measure	MK-1293 n=241 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Basal Insulin Dose Per kg of Body Weight at Week 52	0.46 Units/kg Interval 0.43 to 0.5	0.47 Units/kg Interval 0.43 to 0.5

SECONDARY outcome

Timeframe: Week 52

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Bolus Insulin Dose at Week 52.

Outcome measures

Outcome measures
Measure	MK-1293 n=228 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=240 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Bolus Insulin Dose at Week 52	22.15 Units Interval 19.03 to 25.27	23.65 Units Interval 20.57 to 26.73

SECONDARY outcome

Timeframe: Week 52

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Bolus Insulin Dose per kg of Body Weight at Week 52.

Outcome measures

Outcome measures
Measure	MK-1293 n=228 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=240 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Bolus Insulin Dose Per kg of Body Weight at Week 52	0.28 Units/kg Interval 0.24 to 0.31	0.30 Units/kg Interval 0.26 to 0.33

SECONDARY outcome

Timeframe: Week 24

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Basal Insulin Dose at Week 24.

Outcome measures

Outcome measures
Measure	MK-1293 n=241 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Basal Insulin Dose at Week 24	36.33 Units Interval 33.24 to 39.42	37.07 Units Interval 34.03 to 40.12

SECONDARY outcome

Timeframe: Week 24

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Basal Insulin Dose per kg of Body Weight at Week 24.

Outcome measures

Outcome measures
Measure	MK-1293 n=241 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Basal Insulin Dose Per kg of Body Weight at Week 24	0.46 Units/kg Interval 0.43 to 0.5	0.48 Units/kg Interval 0.44 to 0.51

SECONDARY outcome

Timeframe: Week 24

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Bolus Insulin Dose at Week 24.

Outcome measures

Outcome measures
Measure	MK-1293 n=224 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=235 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Bolus Insulin Dose at Week 24	21.65 Units Interval 18.5 to 24.81	22.91 Units Interval 19.8 to 26.02

SECONDARY outcome

Timeframe: Week 24

Population: The analysis population included all randomized, treated participants who had at least one observation for the analysis endpoint.

Bolus Insulin Dose per kg of Body Weight at Week 24.

Outcome measures

Outcome measures
Measure	MK-1293 n=224 Participants MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=235 Participants Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Bolus Insulin Dose Per kg of Body Weight at Week 24	0.28 Units/kg Interval 0.24 to 0.31	0.29 Units/kg Interval 0.26 to 0.33

Adverse Events

MK-1293

Serious events: 23 serious events

Other events: 190 other events

Deaths: 0 deaths

Lantus

Serious events: 30 serious events

Other events: 216 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	MK-1293 n=241 participants at risk MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 participants at risk Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Infections and infestations Nasopharyngitis	7.9% 19/241 • Number of events 23 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	8.9% 23/258 • Number of events 29 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Infections and infestations Upper respiratory tract infection	11.2% 27/241 • Number of events 40 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	10.9% 28/258 • Number of events 34 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypoglycaemia	76.8% 185/241 • Number of events 7617 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	79.1% 204/258 • Number of events 7544 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study 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 study 60 days prior to submission for publication/ presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK-1293 n=241 participants at risk MK-1293 dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).	Lantus n=258 participants at risk Lantus dosed subcutaneously once daily at bedtime for 52 weeks. Doses were individually titrated post-randomization to the suggested target for fasting fingerstick glucose levels of \>70 mg/dL (3.9 mmol/L) and ≤100 mg/dL (5.6 mmol/L).
Cardiac disorders Angina unstable	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Cardiac disorders Cardiac failure congestive	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 2 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastric haemorrhage	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Gastrointestinal disorders Intestinal obstruction	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Hepatobiliary disorders bile duct stone	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Hepatobiliary disorders Cholecystitis	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Hepatobiliary disorders Cholecystitis acute	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Infections and infestations Postoperative wound infection	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Infections and infestations Pneumonia	0.83% 2/241 • Number of events 2 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Infections and infestations Oseomyelitis	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Laceration	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.78% 2/258 • Number of events 2 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hypoglycaemia	2.1% 5/241 • Number of events 8 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	4.3% 11/258 • Number of events 14 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian adenoma	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Epilepsy	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Hypoglycaemic seizure	0.83% 2/241 • Number of events 4 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	1.6% 4/258 • Number of events 4 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Hypoglycaemic unconsciousness	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.78% 2/258 • Number of events 2 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Seizure	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Syncope	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Nervous system disorders VIth nerve paresis	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 3 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Skin and subcutaneous tissue disorders Diabetic foot	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Vascular disorders Aortic aneurysm	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Vascular disorders Peripheral vascular disorder	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Ankle fracture	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Cardiac disorders Coronary artery stenosis	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Cardiac disorders Myocardial infarction	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Infections and infestations Localised infection	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Cardiac disorders Acute myocardial infarction	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Cardiac disorders Angina pectoris	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.78% 2/258 • Number of events 2 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Infections and infestations Cellulitis	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.41% 1/241 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.00% 0/258 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.
Nervous system disorders Transient ischaemic attack	0.00% 0/241 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.	0.39% 1/258 • Number of events 1 • Up to 54 weeks The safety population consisted of all randomized participants who received at least one dose of study treatment.