Trial Outcomes & Findings for Efficacy and Safety of Alirocumab Versus Usual Care on Top of Maximally Tolerated Statin Therapy in Patients With Type 2 Diabetes and Mixed Dyslipidemia (ODYSSEY DM-Dyslipidemia) (NCT NCT02642159)

NCT ID: NCT02642159

Last Updated: 2018-05-01

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 8 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 413 participants
• Primary outcome timeframe: From Baseline to Week 24
• Results posted on: 2018-05-01

Participant Flow

The study was conducted at 119 centers in 15 countries. A total of 864 participants were screened between March 2016 and September 2016, 451 of whom were screen failures. Screen failures were mainly due to inclusion criteria not met.

Randomization was stratified by investigator's choice of usual care therapy, which was pre-specified prior to randomization. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 2:1 ratio (alirocumab: usual care) after confirmation of selection criteria. 413 participants were randomized.

Participant milestones

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W Alirocumab 75 mg subcutaneous (SC) injection every 2 weeks (Q2W) added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other lipid modifying therapies (LMT) for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-high-density lipoprotein cholesterol (non-HDL-C) levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Study STARTED	276	137
Overall Study Treated (Safety Population)	275	137
Overall Study ITT Population	273	136
Overall Study ITT: Intent to Prescribe Fenofibrate	47	24
Overall Study COMPLETED	245	129
Overall Study NOT COMPLETED	31	8

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 insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other lipid modifying therapies (LMT) for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-high-density lipoprotein cholesterol (non-HDL-C) levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Overall Study Randomized but not treated	1	0
Overall Study Adverse Event	10	4
Overall Study Withdrawal by Subject	9	1
Overall Study Poor compliance to study protocol	1	0
Overall Study Other than specified above	10	3

Baseline Characteristics

Efficacy and Safety of Alirocumab Versus Usual Care on Top of Maximally Tolerated Statin Therapy in Patients With Type 2 Diabetes and Mixed Dyslipidemia (ODYSSEY DM-Dyslipidemia)

Baseline characteristics by cohort

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=276 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=137 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.	Total n=413 Participants Total of all reporting groups
Age, Continuous	62.8 years STANDARD_DEVIATION 9.3 • n=5 Participants	64.1 years STANDARD_DEVIATION 8.8 • n=7 Participants	63.2 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	129 Participants n=5 Participants	68 Participants n=7 Participants	197 Participants n=5 Participants
Sex: Female, Male Male	147 Participants n=5 Participants	69 Participants n=7 Participants	216 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	35 Participants n=5 Participants	14 Participants n=7 Participants	49 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	240 Participants n=5 Participants	123 Participants n=7 Participants	363 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	247 Participants n=5 Participants	123 Participants n=7 Participants	370 Participants n=5 Participants
Race/Ethnicity, Customized Black	16 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Asian/Oriental	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Non-HDL-C	4.0 mmol/L STANDARD_DEVIATION 1.2 • n=5 Participants	4.2 mmol/L STANDARD_DEVIATION 1.2 • n=7 Participants	4.073 mmol/L STANDARD_DEVIATION 1.221 • n=5 Participants
Intent to Prescribe Treatment Fenofibrate	48 Participants n=5 Participants	24 Participants n=7 Participants	72 Participants n=5 Participants
Intent to Prescribe Treatment No additional LMT	79 Participants n=5 Participants	39 Participants n=7 Participants	118 Participants n=5 Participants
Intent to Prescribe Treatment Ezetimibe	104 Participants n=5 Participants	52 Participants n=7 Participants	156 Participants n=5 Participants
Intent to Prescribe Treatment Omega-3 fatty acids	43 Participants n=5 Participants	21 Participants n=7 Participants	64 Participants n=5 Participants
Intent to Prescribe Treatment Nicotinic acid	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 24

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

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 8 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Non-HDL-C at Week 24: Overall Intent-to-treat (ITT) Analysis	-37.3 Percent change Standard Error 3.0	-4.7 Percent change Standard Error 3.3

PRIMARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population. Here, 'Number of participants analyzed' = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=47 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=24 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Non-HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum	-41.7 Percent change Standard Error 3.4	-8.5 Percent change Standard Error 4.8

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 value on-or off-treatment (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 8 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Measured Low-Density Lipoprotein Cholesterol (LDL-C) at Week 24: Overall ITT Analysis	-43.3 Percent change Standard Error 3.6	-0.3 Percent change Standard Error 4.0

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: LDL-C ITT population. Here, 'Number of participants analyzed' = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.

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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=47 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=24 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Measured LDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum	-47.0 Percent change Standard Error 4.2	8.7 Percent change Standard Error 5.8

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Non-HDL-C at Week 12: Overall ITT Analysis	-35.5 Percent change Standard Error 2.9	-9.4 Percent change Standard Error 3.2

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population. Here, 'Number of participants analyzed' = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.

Adjusted LS means and standard errors at Week 12 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=47 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=24 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Non-HDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum	-34.7 Percent change Standard Error 3.2	-7.3 Percent change Standard Error 4.5

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: LDL-C ITT population.

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 8 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Measured LDL-C at Week 12: Overall ITT Analysis	-41.7 Percent change Standard Error 3.3	-7.0 Percent change Standard Error 3.6

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: LDL-C ITT population. Here, 'Number of participants analyzed' = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.

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 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=47 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=24 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Measured LDL-C at Week 12: ITT- Intent to Prescribe Fenofibrate Stratum	-44.3 Percent change Standard Error 3.6	5.4 Percent change Standard Error 5.1

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 8 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24: Overall ITT Analysis	-33.8 Percent change Standard Error 2.7	-1.6 Percent change Standard Error 3.0

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Apo-B ITT population.Here, 'Number of participants analyzed' = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=47 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=24 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Apo B at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum	-38.9 Percent change Standard Error 3.1	-3.8 Percent change Standard Error 4.4

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 8 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 : Overall ITT Analysis	-27.4 Percent change Standard Error 2.3	-2.8 Percent change Standard Error 2.5

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: Total-C ITT population. Here, 'Number of participants analyzed' = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=47 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=24 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Total-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum	-30.9 Percent change Standard Error 2.6	-5.7 Percent change Standard Error 3.7

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 followed by robust regression model for handling of missing data. All available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment were included in the imputation model.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Lipoprotein(a) at Week 24 : Overall ITT Analysis	-23.7 Percent change Standard Error 1.9	3.7 Percent change Standard Error 2.6

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population. Here, 'Number of participants analyzed' = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.

Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=47 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=24 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Lipoprotein(a) at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum	-18.9 Percent change Standard Error 4.4	3.9 Percent change Standard Error 6.6

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population.

Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Fasting Triglycerides at Week 24: Overall ITT Analysis	-13.0 Percent change Standard Error 2.0	-8.8 Percent change Standard Error 2.8

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: ITT population. Here, 'Number of participants analyzed' = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.

Adjusted means and standard errors at Week 24 from multiple imputation approach followed by robust regression model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=47 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=24 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in Fasting Triglycerides at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum	-15.4 Percent change Standard Error 4.7	-24.4 Percent change Standard Error 6.6

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 8 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in HDL-C at Week 24 : Overall ITT Analysis	14.5 Percent change Standard Error 2.5	8.2 Percent change Standard Error 2.7

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: HDL-C ITT population. Here, 'Number of participants analyzed' = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.

Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=47 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=24 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in HDL-C at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum	13.5 Percent change Standard Error 2.9	12.3 Percent change Standard Error 4.1

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 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 8 to Week 24 regardless of status on- or off-treatment.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=270 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=135 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in LDL-C Particle Number at Week 24: Overall ITT Analysis	-41.6 Percent change Standard Error 3.0	-3.9 Percent change Standard Error 3.4

SECONDARY outcome

Timeframe: From Baseline to Week 24

Population: LDL-C particle number ITT population. Here, 'Number of participants analyzed' = participants from intent to prescribe fenofibrate stratum who were evaluable for this outcome measure.

LDL-C particle number was calculated from lipid subfractions by NMR spectroscopy. Adjusted LS means and standard errors at Week 24 from MMRM model including all available post-baseline data from Week 8 to Week 24 regardless of status on- or off-treatment in the intent to prescribe fenofibrate stratum. The usual care here corresponds to fenofibrate.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=46 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=24 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Percent Change From Baseline in LDL-C Particle Number at Week 24: ITT- Intent to Prescribe Fenofibrate Stratum	-45.4 Percent change Standard Error 3.5	-2.9 Percent change Standard Error 5.0

SECONDARY outcome

Timeframe: Baseline, Week 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 week minus HbA1c value at baseline.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Absolute Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 and 24 : Overall ITT Analysis Change at Week 12	0.59 mmol/mol Standard Deviation 6.82	0.43 mmol/mol Standard Deviation 5.70
Absolute Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 and 24 : Overall ITT Analysis Change at Week 24	2.84 mmol/mol Standard Deviation 8.04	2.40 mmol/mol Standard Deviation 8.19

SECONDARY outcome

Timeframe: Baseline, Week 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 week minus FPG value at baseline.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 and 24 : Overall ITT Analysis Change at Week 12	0.45 mmol/L Standard Deviation 2.43	0.21 mmol/L Standard Deviation 1.86
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 and 24 : Overall ITT Analysis Change at Week 24	0.68 mmol/L Standard Deviation 2.54	0.03 mmol/L Standard Deviation 2.54

SECONDARY outcome

Timeframe: Baseline, Week 12 and 24

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

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 week minus baseline value.

Outcome measures

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=273 Participants Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=136 Participants Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Week 12 and 24 : Overall ITT Analysis Change at Week 12	0.04 Glucose lowering treatments Standard Deviation 0.30	0.04 Glucose lowering treatments Standard Deviation 0.19
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Week 12 and 24 : Overall ITT Analysis Change at Week 24	0.07 Glucose lowering treatments Standard Deviation 0.37	0.04 Glucose lowering treatments Standard Deviation 0.23

Adverse Events

Alirocumab 75 mg Q2W/Up to 150 mg Q2W

Serious events: 26 serious events

Other events: 37 other events

Deaths: 1 deaths

Usual Care

Serious events: 12 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=275 participants at risk Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=137 participants at risk Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Cardiac disorders Acute myocardial infarction	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.73% 1/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Cardiac disorders Angina unstable	1.1% 3/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Cardiac disorders Coronary artery disease	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Ear and labyrinth disorders Vertigo	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Eye disorders Glaucoma	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Gastrointestinal disorders Gastrooesophageal reflux disease	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Gastrointestinal disorders Rectal haemorrhage	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Gastrointestinal disorders Small intestinal obstruction	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
General disorders Death	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
General disorders Non-cardiac chest pain	0.73% 2/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Hepatobiliary disorders Cholecystitis acute	0.00% 0/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.73% 1/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Infections and infestations Appendicitis	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Infections and infestations Diabetic foot infection	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Infections and infestations Osteomyelitis	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Infections and infestations Pneumonia	0.73% 2/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Infections and infestations Urinary tract infection	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Injury, poisoning and procedural complications Lower limb fracture	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.73% 1/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.73% 1/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.73% 1/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Nervous system disorders Cerebrovascular accident	0.00% 0/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.73% 1/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Nervous system disorders Dizziness	0.00% 0/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.73% 1/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Nervous system disorders Facial paralysis	0.00% 0/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.73% 1/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Nervous system disorders Ischaemic stroke	0.73% 2/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	1.5% 2/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Nervous system disorders Seizure	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Nervous system disorders Transient ischaemic attack	0.00% 0/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.73% 1/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Psychiatric disorders Bipolar I disorder	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Renal and urinary disorders Acute kidney injury	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Renal and urinary disorders Nephrolithiasis	0.36% 1/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.00% 0/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Reproductive system and breast disorders Vaginal prolapse	0.00% 0/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	0.73% 1/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).

Other adverse events

Measure	Alirocumab 75 mg Q2W/Up to 150 mg Q2W n=275 participants at risk Alirocumab 75 mg SC injection Q2W added to insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without other LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when non-HDL-C levels \>=100 mg/dL (2.59 mmol/L) at Week 8.	Usual Care n=137 participants at risk Participants on usual care continued on insulin or other antihyperglycemic drugs, stable maximally tolerated dose of statin therapy without additional LMT or with either ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid as per Investigator's judgment for 24 weeks.
Gastrointestinal disorders Diarrhoea	5.1% 14/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	6.6% 9/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Infections and infestations Bronchitis	1.8% 5/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	5.1% 7/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Infections and infestations Urinary tract infection	5.5% 15/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	3.6% 5/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).
Musculoskeletal and connective tissue disorders Arthralgia	2.2% 6/275 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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).	5.8% 8/137 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 32) regardless of seriousness or relationship to investigational product. Reported AEs and deaths are TEAEs that are 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: Contact-US@sanofi.com

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