Trial Outcomes & Findings for Efficacy and Safety of Alirocumab Versus Placebo on Top of Maximally Tolerated Lipid Lowering Therapy in Patients With Hypercholesterolemia Who Have Type 1 or Type 2 Diabetes and Are Treated With Insulin (ODYSSEY DM - Insulin) (NCT NCT02585778)

Last Updated: 2018-05-17

Results Overview

Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

517 participants

Primary outcome timeframe

From Baseline to Week 24

Results posted on

2018-05-17

Participant Flow

The study was conducted at 103 sites in 10 countries. Of these, 97 active sites randomized at least 1 participant. Overall 796 participants were screened between October 2015 and August 2016, of whom 279 were screen failures. Screen failures were mainly due to exclusion criteria met or inclusion criteria not met.

Randomization was stratified by diabetes type (Type 1 diabetes mellitus \[T1DM\] versus Type 2 diabetes mellitus \[T2DM\]). Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 2:1 ratio (Alirocumab:Placebo). A total of 517 participants were randomized. Baseline and efficacy data were analyzed per stratum.

Participant milestones

Participant milestones
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to stable, maximally tolerated dose of statin therapy with or without other lipid-modifying therapy (LMT), insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Overall Study STARTED	345	172
Overall Study Treated (Safety Population)	344	170
Overall Study ITT Population	336	167
Overall Study mITT Population	333	164
Overall Study T1DM Participants	51	25
Overall Study T2DM Participants	294	147
Overall Study COMPLETED	312	157
Overall Study NOT COMPLETED	33	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to stable, maximally tolerated dose of statin therapy with or without other lipid-modifying therapy (LMT), insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Overall Study Adverse Event	17	4
Overall Study Participant did not wish to continue	9	4
Overall Study Poor compliance to study protocol	0	2
Overall Study Death	0	1
Overall Study Randomized but not treated	1	2
Overall Study Other than specified above	6	2

Baseline Characteristics

Efficacy and Safety of Alirocumab Versus Placebo on Top of Maximally Tolerated Lipid Lowering Therapy in Patients With Hypercholesterolemia Who Have Type 1 or Type 2 Diabetes and Are Treated With Insulin (ODYSSEY DM - Insulin)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=51 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=294 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=147 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Total n=517 Participants Total of all reporting groups
Age, Continuous	54.9 years STANDARD_DEVIATION 10.1 • n=99 Participants	58.5 years STANDARD_DEVIATION 7.8 • n=107 Participants	63.9 years STANDARD_DEVIATION 8.9 • n=206 Participants	64.0 years STANDARD_DEVIATION 9.4 • n=7 Participants	62.8 years STANDARD_DEVIATION 9.6 • n=31 Participants
Sex: Female, Male Female	22 Participants n=99 Participants	8 Participants n=107 Participants	133 Participants n=206 Participants	69 Participants n=7 Participants	232 Participants n=31 Participants
Sex: Female, Male Male	29 Participants n=99 Participants	17 Participants n=107 Participants	161 Participants n=206 Participants	78 Participants n=7 Participants	285 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants	0 Participants n=107 Participants	13 Participants n=206 Participants	8 Participants n=7 Participants	22 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 Participants n=99 Participants	25 Participants n=107 Participants	280 Participants n=206 Participants	138 Participants n=7 Participants	493 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants	2 Participants n=31 Participants
Race/Ethnicity, Customized White/Caucasian	50 Participants n=99 Participants	24 Participants n=107 Participants	259 Participants n=206 Participants	135 Participants n=7 Participants	468 Participants n=31 Participants
Race/Ethnicity, Customized Black	1 Participants n=99 Participants	0 Participants n=107 Participants	27 Participants n=206 Participants	7 Participants n=7 Participants	35 Participants n=31 Participants
Race/Ethnicity, Customized Asian/Oriental	0 Participants n=99 Participants	0 Participants n=107 Participants	7 Participants n=206 Participants	3 Participants n=7 Participants	10 Participants n=31 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race/Ethnicity, Customized Other	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	2 Participants n=7 Participants	4 Participants n=31 Participants
Calculated LDL-C in mg/dL	126.4 mg/dL STANDARD_DEVIATION 58.2 • n=99 Participants	110.2 mg/dL STANDARD_DEVIATION 31.2 • n=107 Participants	110.8 mg/dL STANDARD_DEVIATION 36.5 • n=206 Participants	109.6 mg/dL STANDARD_DEVIATION 39.1 • n=7 Participants	112.0 mg/dL STANDARD_DEVIATION 39.8 • n=31 Participants
Calculated LDL-C in mmol/L	3.273 mmol/L STANDARD_DEVIATION 1.506 • n=99 Participants	2.853 mmol/L STANDARD_DEVIATION 0.807 • n=107 Participants	2.871 mmol/L STANDARD_DEVIATION 0.944 • n=206 Participants	2.838 mmol/L STANDARD_DEVIATION 1.013 • n=7 Participants	2.900 mmol/L STANDARD_DEVIATION 1.031 • n=31 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population: all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=287 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=142 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis	-51.8 percent change Standard Error 3.7	-3.9 percent change Standard Error 5.3	-48.2 percent change Standard Error 1.6	0.8 percent change Standard Error 2.2

PRIMARY outcome

Timeframe: From Baseline up to 10 weeks after last study drug administration (maximum of 32 weeks)

Population: Safety population: all randomized participants who received at least one dose or part of a dose of a study drug (treated).

Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=344 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=170 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) Any AE	64.5 percentage of participants	64.1 percentage of participants	—	—
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) Any Serious AE	9.0 percentage of participants	9.4 percentage of participants	—	—
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) Any AE leading to death	0 percentage of participants	0.6 percentage of participants	—	—
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs) Any AE leading to treatment discontinuation	4.9 percentage of participants	2.4 percentage of participants	—	—

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Modified ITT population (mITT): all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment.

Adjusted LS means and standard errors at Week 24 were obtained from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=24 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=284 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis	-53.8 percent change Standard Error 3.7	-3.2 percent change Standard Error 5.3	-50.9 percent change Standard Error 1.6	0.7 percent change Standard Error 2.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline measured LDL-C value on- or off-treatment (Measured LDL-C ITT population).

Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=47 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=22 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=277 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=139 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis	-49.4 percent change Standard Error 3.7	-1.1 percent change Standard Error 5.4	-43.3 percent change Standard Error 1.6	2.4 percent change Standard Error 2.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment at Week 12 (ITT population at Week 12).

Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=284 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis	-49.4 percent change Standard Error 3.5	-4.5 percent change Standard Error 5.0	-48.8 percent change Standard Error 1.4	1.4 percent change Standard Error 2.1

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline measured LDL-C value on- or off-treatment at Week 12 (Measured LDL-C ITT population at Week 12).

Measured LDL-C values via beta quantification method. Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=45 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=22 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=275 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=136 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis	-46.7 percent change Standard Error 3.6	-4.0 percent change Standard Error 5.1	-44.8 percent change Standard Error 1.4	-0.8 percent change Standard Error 2.0

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline non-HDL-C value on- or off-treatment (non-HDL-C ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=287 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=142 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis	-45.9 percent change Standard Error 3.3	-3.2 percent change Standard Error 4.8	-37.9 percent change Standard Error 1.4	0.7 percent change Standard Error 2.0

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline Apo B value on- or off-treatment (Apo B ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=47 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=22 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=279 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis	-39.4 percent change Standard Error 3.0	-0.4 percent change Standard Error 4.3	-33.4 percent change Standard Error 1.3	3.3 percent change Standard Error 1.7

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline total-C value on- or off-treatment (Total-C ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=287 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=142 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis	-29.9 percent change Standard Error 2.5	-0.7 percent change Standard Error 3.6	-26.8 percent change Standard Error 1.0	0.8 percent change Standard Error 1.5

SECONDARY outcome

Timeframe: Up to Week 24

Population: mITT population.

Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=24 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=284 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis	70.2 percentage of participants	5.1 percentage of participants	76.4 percentage of participants	7.4 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: mITT population.

Adjusted percentages at Week 24 from last observation carried forward (LOCF) approach (for T1DM participants) and multiple imputation approach model (for T2DM participants) including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection). The maximum likelihood estimate did not exist as response rate was zero in a treatment group of T1DM participants.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=24 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=284 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis	55.1 percentage of participants	0 percentage of participants	50.7 percentage of participants	2.7 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: Participants of the mITT population with one baseline and at least one post-baseline Non-HDL-C value on-treatment (Non-HDL-C mITT population).

Adjusted percentages at Week 24 from multiple imputation approach model including available post-baseline data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=24 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=284 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis	79.0 percentage of participants	22.9 percentage of participants	70.9 percentage of participants	13.8 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 24

Population: Non-HDL-C mITT population.

Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection).

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=24 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=284 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis	59.6 percentage of participants	5.3 percentage of participants	52.3 percentage of participants	1.7 percentage of participants

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

Adjusted means and standard errors at Week 24 were obtained from multiple imputation approach for handling of missing data followed by robust regression model. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included in the imputation model.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=287 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=142 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis	-23.0 percent change Standard Error 3.8	-4.3 percent change Standard Error 5.3	-19.0 percent change Standard Error 1.6	-0.5 percent change Standard Error 2.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline HDL-C value on- or off-treatment (HDL-C ITT population).

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=287 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=142 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis	11.2 percent change Standard Error 2.4	7.3 percent change Standard Error 3.5	8.1 percent change Standard Error 1.0	3.7 percent change Standard Error 1.4

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

Adjusted means and standard errors at Week 24 from multiple imputation approach for handling of missing data followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=287 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=142 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis	-13.6 percent change Standard Error 4.7	1.9 percent change Standard Error 6.7	-5.7 percent change Standard Error 2.0	0.0 percent change Standard Error 2.7

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline LDL-C particle number value on- or off-treatment (LDL-C particle number ITT population).

LDL-C particle number was calculated from lipid subfractions by nuclear magnetic resonance (NMR) spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=45 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=22 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=272 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=134 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis	-44.4 percent change Standard Error 3.2	-4.4 percent change Standard Error 4.6	-38.3 percent change Standard Error 1.3	1.9 percent change Standard Error 1.9

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Participants of the ITT population with one baseline and at least one post-baseline LDL-C particle size value on- or off-treatment (LDL-C particle size ITT population).

LDL-C particle size was calculated from lipid subfractions by NMR spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=44 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=22 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=267 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=134 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis	-2.3 percent change Standard Error 0.3	0.8 percent change Standard Error 0.5	-2.8 percent change Standard Error 0.1	-0.3 percent change Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: ITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=287 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=142 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis Change at Week 12	0.00 percentage of hemoglobin Standard Deviation 0.46	-0.22 percentage of hemoglobin Standard Deviation 0.39	-0.04 percentage of hemoglobin Standard Deviation 0.57	0.00 percentage of hemoglobin Standard Deviation 0.58
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis Change at Week 24	-0.03 percentage of hemoglobin Standard Deviation 0.60	-0.23 percentage of hemoglobin Standard Deviation 0.36	0.18 percentage of hemoglobin Standard Deviation 0.74	0.06 percentage of hemoglobin Standard Deviation 0.66

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: mITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=24 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=284 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis Change at Week 12	0.00 percentage of hemoglobin Standard Deviation 0.46	-0.22 percentage of hemoglobin Standard Deviation 0.39	-0.04 percentage of hemoglobin Standard Deviation 0.57	0.00 percentage of hemoglobin Standard Deviation 0.59
Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis Change at Week 24	-0.05 percentage of hemoglobin Standard Deviation 0.61	-0.27 percentage of hemoglobin Standard Deviation 0.34	0.18 percentage of hemoglobin Standard Deviation 0.74	0.06 percentage of hemoglobin Standard Deviation 0.67

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: ITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Absolute change = FPG value at specified weeks minus FPG value at baseline.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=287 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=142 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis Change at Week 12	0.23 mmol/L Standard Deviation 4.44	0.45 mmol/L Standard Deviation 4.73	0.25 mmol/L Standard Deviation 2.73	0.13 mmol/L Standard Deviation 2.73
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis Change at Week 24	0.52 mmol/L Standard Deviation 5.20	0.81 mmol/L Standard Deviation 4.21	0.52 mmol/L Standard Deviation 3.43	0.55 mmol/L Standard Deviation 2.62

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: mITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Absolute change = FPG value at specified weeks minus FPG value at baseline.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=24 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=284 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis Change at Week 12	0.23 mmol/L Standard Deviation 4.44	0.45 mmol/L Standard Deviation 4.73	0.22 mmol/L Standard Deviation 2.70	0.15 mmol/L Standard Deviation 2.74
Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis Change at Week 24	0.38 mmol/L Standard Deviation 5.24	0.71 mmol/L Standard Deviation 4.19	0.52 mmol/L Standard Deviation 3.47	0.48 mmol/L Standard Deviation 2.53

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: ITT population . Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Absolute change = total daily insulin dose at specified weeks minus baseline value.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=287 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=142 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis Change at Week 12	-10.0 units (U) Standard Deviation 48.7	-1.3 units (U) Standard Deviation 9.6	0.2 units (U) Standard Deviation 7.9	1.4 units (U) Standard Deviation 11.4
Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis Change at Week 24	-2.2 units (U) Standard Deviation 11.3	-0.8 units (U) Standard Deviation 9.8	2.2 units (U) Standard Deviation 14.8	1.6 units (U) Standard Deviation 11.4

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: mITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Absolute change = total daily insulin dose at specified weeks minus baseline value.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=24 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=284 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis Change at Week 12	-10.0 units (U) Standard Deviation 48.7	-1.3 units (U) Standard Deviation 9.6	0.2 units (U) Standard Deviation 7.9	1.4 units (U) Standard Deviation 11.4
Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis Change at Week 24	-2.2 units (U) Standard Deviation 11.3	-0.8 units (U) Standard Deviation 9.8	1.7 units (U) Standard Deviation 11.7	1.6 units (U) Standard Deviation 11.5

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: ITT population . Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Absolute change = daily insulin dose/kg at specified weeks minus baseline value.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=287 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=142 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis Change at Week 12	-0.1 U/kg Standard Deviation 0.5	0.0 U/kg Standard Deviation 0.1	0.0 U/kg Standard Deviation 0.1	0.0 U/kg Standard Deviation 0.1
Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis Change at Week 24	0.0 U/kg Standard Deviation 0.1	0.0 U/kg Standard Deviation 0.1	0.0 U/kg Standard Deviation 0.2	0.0 U/kg Standard Deviation 0.1

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: mITT population. Here, 'Number Analyzed' = participants with available data at the specified time points for each arm, respectively.

Absolute change = daily insulin dose/kg at specified weeks minus baseline value.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=24 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=284 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis Change at Week 12	-0.1 U/kg Standard Deviation 0.5	0.0 U/kg Standard Deviation 0.1	0.0 U/kg Standard Deviation 0.1	0.0 U/kg Standard Deviation 0.1
Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis Change at Week 24	0.0 U/kg Standard Deviation 0.1	0.0 U/kg Standard Deviation 0.1	0.0 U/kg Standard Deviation 0.1	0.0 U/kg Standard Deviation 0.1

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: ITT population.

Glucose lowering treatment was calculated for non-insulin treatments as one for each unique treatment received and for insulin treatment as one in total for all participants who have taken one or more treatments. Absolute change = number of glucose-lowering treatments at specified weeks minus baseline value.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=25 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=287 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=142 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis Change at Week 12	0 glucose lowering treatments Standard Deviation 0	0 glucose lowering treatments Standard Deviation 0	0 glucose lowering treatments Standard Deviation 0.1	0 glucose lowering treatments Standard Deviation 0.2
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis Change at Week 24	0 glucose lowering treatments Standard Deviation 0	0 glucose lowering treatments Standard Deviation 0	0 glucose lowering treatments Standard Deviation 0.3	0 glucose lowering treatments Standard Deviation 0.2

SECONDARY outcome

Timeframe: Baseline, Weeks 12 and 24

Population: mITT population.

Outcome measures

Outcome measures
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants n=49 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T1DM Participants n=24 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants n=284 Participants Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W: T2DM Participants n=140 Participants Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis Change at Week 24	0 glucose lowering treatments Standard Deviation 0	0 glucose lowering treatments Standard Deviation 0	0 glucose lowering treatments Standard Deviation 0.3	0 glucose lowering treatments Standard Deviation 0.2
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis Change at Week 12	0 glucose lowering treatments Standard Deviation 0	0 glucose lowering treatments Standard Deviation 0	0 glucose lowering treatments Standard Deviation 0.1	0 glucose lowering treatments Standard Deviation 0.2

Adverse Events

Alirocumab 75 mg Q2W/Up to 150 mg Q2W

Serious events: 31 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo Q2W

Serious events: 16 serious events

Other events: 9 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=344 participants at risk Alirocumab 75 mg SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.	Placebo Q2W n=170 participants at risk Placebo (for alirocumab) SC injection Q2W added to stable, maximally tolerated dose of statin therapy with or without other LMT, insulin alone or with other antihyperglycemic drugs for 24 weeks.
Infections and infestations Nasopharyngitis	4.9% 17/344 • All Adverse Events (AE) were collected from signature of the informed consent form up to final visit (Week 32) in the study regardless of seriousness or relationship to study drugs. Reported AEs and deaths are TEAEs that is AEs that developed/worsened and death that occurred during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).	5.3% 9/170 • All Adverse Events (AE) were collected from signature of the informed consent form up to final visit (Week 32) in the study regardless of seriousness or relationship to study drugs. Reported AEs and deaths are TEAEs that is AEs that developed/worsened and death that occurred during the 'treatment-emergent period' (the time from the first dose of study drug up to the last dose of study drug +70 days).

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER