CompletedNCT02585778Updated May 17, 2018Results posted

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)

A Phase 3 interventional study of Alirocumab and Placebo in Hypercholesterolaemia, sponsored by Sanofi. Completed at 110 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-05-17.

Sponsored by Sanofi · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 517
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

Primary Objectives:

To demonstrate the superiority of alirocumab in comparison with placebo in the reduction of calculated low-density lipoprotein cholesterol (LDL-C) in participants with diabetes treated with insulin and with hypercholesterolemia at high cardiovascular risk not adequately controlled on maximally tolerated LDL-C lowering therapy.
To evaluate the safety and tolerability of alirocumab in participants with diabetes treated with insulin.

Secondary Objective:

To demonstrate that alirocumab was superior in comparison to placebo in its effects on other lipid parameters (i.e., measured LDL-C, non-high-density lipoprotein cholesterol [non-HDL-C], apolipoprotein B [Apo B], total cholesterol [TC], lipoprotein a [Lp(a)], high density lipoprotein cholesterol [HDL-C], triglyceride [TG] levels, triglyceride rich lipoproteins [TGRL], apolipoprotein A-1 [Apo A-1], apolipoprotein C-III [Apo C-III], and LDL particle number and size).

Read the detailed description

The maximum study duration was approximately 9 months per participant, including a 6 month treatment period, a screening period of up to 3 weeks, and an 8 week safety observation period.

Conditions studied

Hypercholesterolaemia

Browse trials for

Hypercholesterolemia 1,238

In context

Hypercholesterolemia

1,238 studies on the registry are indexed under Hypercholesterolemia; 110 are open to participants now.

This study's enrollment of 517 is above the median of 100 across 992 interventional studies indexed under Hypercholesterolemia.

Browse Hypercholesterolemia studies →

Lead sponsor

Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.

Of its 198 completed or terminated interventional studies of FDA-regulated products, 118 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Participants diagnosed with Type 1 or Type 2 diabetes at least one year prior to the screening visit (Week -3).
Signed written informed consent
Participants with type 1 or type 2 diabetes treated with insulin whose LDL-C levels were not adequately controlled with maximally tolerated lipid-modifying therapy
LDL-C of 70 mg/dL or greater
18 years of age or more
Glycosylated hemoglobin (HbA1c) less than 10%
History of cardiovascular disease (including coronary heart disease [CHD] and/or CHD risk equivalents) and/or at least one additional cardiovascular risk factor

Exclusion criteria

Exclusion criteria:

Not on a stable dose of statin or other lipid modifying therapy for at least 4 weeks prior to screening or from screening to randomization, unless statin intolerant
Triglycerides >400 mg/dL
Estimated glomerular filtration rate (eGFR) \<15 mL/min/1.73 m² according to the Modification of Diet in Renal Disease (MDRD) equation
Currently received or planned to receive renal replacement therapy (for example, hemodialysis)
Change in weight of more than 5 kilograms within the prior 2 months
Not on a stable dose/regimen of insulin or other antidiabetic drugs for the past 3 months or planned to intensify insulin regimen during the study
Not treated with insulin for at least 6 months
Planned to start new lipid modifying therapy or change dose of current lipid modifying therapy during the study
Body mass index (BMI) >45 kg/m² or planned to undergo bariatric surgery, weight loss program, or initiate weight loss drugs during the study
History of recent decompensation of diabetes within the prior 2 months (for example, diabetic ketoacidosis)

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 517 participants (actual)

Study arms

Experimental
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 LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8.
Drug: Alirocumab · Drug: Lipid-Modifying Therapy (LMT) · Drug: Antihyperglycemic Drug
Placebo comparator
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.
Drug: Placebo · Drug: Lipid-Modifying Therapy (LMT) · Drug: Antihyperglycemic Drug

Interventions

DrugAlirocumab
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.
Also known as: Praluent, SAR236553, REGN727
DrugPlacebo
Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector.
DrugLipid-Modifying Therapy (LMT)
Statins at stable, maximally tolerated dose with or without other LMT as clinically indicated.
DrugAntihyperglycemic Drug
Insulin (injectable or inhaled) alone or with other antihyperglycemic drugs as clinically indicated.

What researchers measure

Primary outcomes

Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis
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).
Time frame: From Baseline to Week 24
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)
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).
Time frame: From Baseline up to 10 weeks after last study drug administration (maximum of 32 weeks)

Secondary outcomes

Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
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).
Time frame: From Baseline to Week 24
Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
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).
Time frame: Up to Week 24
Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis
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.
Time frame: Up to Week 24
Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis
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).
Time frame: Up to Week 24
Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis
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).
Time frame: Up to Week 24
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis
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.
Time frame: From Baseline to Week 24
Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis
Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis
Absolute change = HbA1c value at specified weeks minus HbA1c value at baseline.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis
Absolute change = FPG value at specified weeks minus FPG value at baseline.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis
Absolute change = FPG value at specified weeks minus FPG value at baseline.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis
Absolute change = total daily insulin dose at specified weeks minus baseline value.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis
Absolute change = total daily insulin dose at specified weeks minus baseline value.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis
Absolute change = daily insulin dose/kg at specified weeks minus baseline value.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis
Absolute change = daily insulin dose/kg at specified weeks minus baseline value.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis
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.
Time frame: Baseline, Weeks 12 and 24
Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis
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.
Time frame: Baseline, Weeks 12 and 24

Results

Posted May 17, 2018

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.

Participant flow — Overall Study
Milestone	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Placebo Q2W
Started	345	172
Treated (safety population)	344	170
Itt population	336	167
Mitt population	333	164
T1dm participants	51	25
T2dm participants	294	147
Completed	312	157
Not completed	33	15
Withdrew: Adverse event	17	4
Withdrew: Participant did not wish to continue	9	4
Withdrew: Poor compliance to study protocol	0	2
Withdrew: Death	0	1
Withdrew: Randomized but not treated	1	2
Withdrew: Other than specified above	6	2

Outcome measures

PrimaryPercent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis

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).

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-treat (ITT) Analysis	-51.8 ± 3.7	-3.9 ± 5.3	-48.2 ± 1.6	0.8 ± 2.2

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -47.8 · 95% CI -60.7 to -35.0Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -49.0 · 95% CI -54.4 to -43.6Alirocumab vs. Placebo

PrimaryPercentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)

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).

Time frame:: From Baseline up to 10 weeks after last study drug administration (maximum of 32 weeks)
Reported as:: Number · percentage of participants

Percentage of Participants Who Experienced Treatment-Emergent Adverse Events (AEs)
percentage of participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Placebo Q2W
Any AE	64.5	64.1
Any Serious AE	9.0	9.4
Any AE leading to death	0	0.6
Any AE leading to treatment discontinuation	4.9	2.4

SecondaryPercent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis

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).

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis	-53.8 ± 3.7	-3.2 ± 5.3	-50.9 ± 1.6	0.7 ± 2.2

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -50.6 · 95% CI -63.4 to -37.9Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -51.6 · 95% CI -56.9 to -46.4Alirocumab vs. Placebo

SecondaryPercent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis

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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis	-49.4 ± 3.7	-1.1 ± 5.4	-43.3 ± 1.6	2.4 ± 2.2

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -48.4 · 95% CI -61.2 to -35.5Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -45.7 · 95% CI -50.9 to -40.4Alirocumab vs. Placebo

SecondaryPercent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis

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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis	-49.4 ± 3.5	-4.5 ± 5.0	-48.8 ± 1.4	1.4 ± 2.1

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -44.8 · 95% CI -56.9 to -32.8Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -50.2 · 95% CI -55.2 to -45.3Alirocumab vs. Placebo

SecondaryPercent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis

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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in Measured LDL-C at Week 12 - ITT Analysis	-46.7 ± 3.6	-4.0 ± 5.1	-44.8 ± 1.4	-0.8 ± 2.0

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -42.7 · 95% CI -54.9 to -30.5Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -44.1 · 95% CI -49.0 to -39.2Alirocumab vs. Placebo

SecondaryPercent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis

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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis	-45.9 ± 3.3	-3.2 ± 4.8	-37.9 ± 1.4	0.7 ± 2.0

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -42.7 · 95% CI -54.2 to -31.3Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -38.7 · 95% CI -43.4 to -33.9Alirocumab vs. Placebo

SecondaryPercent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis

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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in Apolipoprotein B (Apo-B) at Week 24 - ITT Analysis	-39.4 ± 3.0	-0.4 ± 4.3	-33.4 ± 1.3	3.3 ± 1.7

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -39.0 · 95% CI -49.4 to -28.7Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -36.7 · 95% CI -40.9 to -32.5Alirocumab vs. Placebo

SecondaryPercent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis

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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · percent change

Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis	-29.9 ± 2.5	-0.7 ± 3.6	-26.8 ± 1.0	0.8 ± 1.5

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -29.2 · 95% CI -37.8 to -20.7Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Mixed Models Analysis · p = <0.0001 (Threshold for significance at 0.05 level.) · Ls mean difference: -27.6 · 95% CI -31.2 to -24.1Alirocumab vs. Placebo

SecondaryPercentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis

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).

Time frame:: Up to Week 24
Reported as:: Number · percentage of participants

Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis
percentage of participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis	70.2	5.1	76.4	7.4

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Regression, Logistic · p = <0.0001 (Threshold for significance at 0.05 level.) · Odds ratio (or): 117.0 · 95% CI 13.1 to 1041.8Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Regression, Logistic · p = <0.0001 (Threshold for significance at 0.05 level) · Odds ratio (or): 84.6 · 95% CI 36.5 to 196.1Alirocumab vs. Placebo

SecondaryPercentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis

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.

Time frame:: Up to Week 24
Reported as:: Number · percentage of participants

Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis
percentage of participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percentage of Participants Reaching Calculated LDL-C <50 mg/dL (1.3 mmol/L) at Week 24 - On-Treatment Analysis	55.1	0	50.7	2.7

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Regression, Logistic · p = <0.0001 (Threshold for significance at 0.05 level.) · Odds ratio (or): 52.9 · 95% CI 16.6 to 168.3Alirocumab vs. Placebo

SecondaryPercentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis

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).

Time frame:: Up to Week 24
Reported as:: Number · percentage of participants

Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis
percentage of participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percentage of Participants Reaching Calculated Non-HDL-C <100 mg/dL at Week 24 - On-Treatment Analysis	79.0	22.9	70.9	13.8

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Regression, Logistic · p = <0.0001 (Threshold for significance at 0.05 level.) · Odds ratio (or): 33.2 · 95% CI 8.0 to 137.4Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Regression, Logistic · p = <0.0001 (Threshold for significance at 0.05 level.) · Odds ratio (or): 27.1 · 95% CI 14.2 to 51.5Alirocumab vs. Placebo

SecondaryPercentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis

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).

Time frame:: Up to Week 24
Reported as:: Number · percentage of participants

Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis
percentage of participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percentage of Participants Reaching Calculated Non-HDL-C <80 mg/dL at Week 24 - On-Treatment Analysis	59.6	5.3	52.3	1.7

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Regression, Logistic · p = 0.0002 (Threshold for significance at 0.05 level.) · Odds ratio (or): 55.5 · 95% CI 6.5 to 473.7Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Regression, Logistic · p = <0.0001 (Threshold for significance at 0.05 level.) · Odds ratio (or): 103.3 · 95% CI 24.6 to 433.1Alirocumab vs. Placebo

SecondaryPercent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis

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.

Time frame:: From Baseline to Week 24
Reported as:: Mean · percent change

Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in Lipoprotein(a) at Week 24 - ITT Analysis	-23.0 ± 3.8	-4.3 ± 5.3	-19.0 ± 1.6	-0.5 ± 2.2

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Regression, Robust · p = 0.0039 (Threshold for significance at 0.05 level.) · Adjusted mean difference: -18.7 · 95% CI -31.4 to -6.0Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Regression, Robust · p = <0.0001 (Threshold for significance at 0.05 level.) · Adjusted mean difference: -18.4 · 95% CI -23.7 to -13.2Alirocumab vs. Placebo

SecondaryPercent Change From Baseline in HDL-C at Week 24 - ITT Analysis

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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · percent change

Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis	11.2 ± 2.4	7.3 ± 3.5	8.1 ± 1.0	3.7 ± 1.4

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants vs Placebo Q2W: T1DM Participants · Mixed Models Analysis · p = 0.3434 (Threshold for significance at 0.05 level.) · Ls mean difference: 3.9 · 95% CI -4.2 to 12.0Alirocumab vs. Placebo
Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Mixed Models Analysis · p = 0.0100 (Threshold for significance at 0.05 level.) · Ls mean difference: 4.4 · 95% CI 1.1 to 7.7Alirocumab vs. Placebo

SecondaryPercent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis

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.

Time frame:: From Baseline to Week 24
Reported as:: Mean · percent change

Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis	-13.6 ± 4.7	1.9 ± 6.7	-5.7 ± 2.0	0.0 ± 2.7

Statistical analysis

Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants vs Placebo Q2W: T2DM Participants · Regression, Robust · p = 0.0902 (Threshold for significance at 0.05 level.) · Adjusted mean difference: -5.7 · 95% CI -12.3 to 0.9Alirocumab vs. Placebo

SecondaryPercent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis

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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · percent change

Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in LDL-C Particle Number at Week 24 - ITT Analysis	-44.4 ± 3.2	-4.4 ± 4.6	-38.3 ± 1.3	1.9 ± 1.9

SecondaryPercent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis

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.

Time frame:: From Baseline to Week 24
Reported as:: Least squares mean · percent change

Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis
percent change	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Percent Change From Baseline in LDL-C Particle Size at Week 24 - ITT Analysis	-2.3 ± 0.3	0.8 ± 0.5	-2.8 ± 0.1	-0.3 ± 0.2

SecondaryAbsolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis

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

Time frame:: Baseline, Weeks 12 and 24
Reported as:: Mean · percentage of hemoglobin

Absolute Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Weeks 12 and 24 - ITT Analysis
percentage of hemoglobin	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Change at Week 12	0.00 ± 0.46	-0.22 ± 0.39	-0.04 ± 0.57	0.00 ± 0.58
Change at Week 24	-0.03 ± 0.60	-0.23 ± 0.36	0.18 ± 0.74	0.06 ± 0.66

SecondaryAbsolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis

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

Time frame:: Baseline, Weeks 12 and 24
Reported as:: Mean · percentage of hemoglobin

Absolute Change From Baseline in HbA1c at Weeks 12 and 24 - On-Treatment Analysis
percentage of hemoglobin	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Change at Week 12	0.00 ± 0.46	-0.22 ± 0.39	-0.04 ± 0.57	0.00 ± 0.59
Change at Week 24	-0.05 ± 0.61	-0.27 ± 0.34	0.18 ± 0.74	0.06 ± 0.67

SecondaryAbsolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis

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

Time frame:: Baseline, Weeks 12 and 24
Reported as:: Mean · mmol/L

Absolute Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 24 - ITT Analysis
mmol/L	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Change at Week 12	0.23 ± 4.44	0.45 ± 4.73	0.25 ± 2.73	0.13 ± 2.73
Change at Week 24	0.52 ± 5.20	0.81 ± 4.21	0.52 ± 3.43	0.55 ± 2.62

SecondaryAbsolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis

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

Time frame:: Baseline, Weeks 12 and 24
Reported as:: Mean · mmol/L

Absolute Change From Baseline in FPG at Weeks 12 and 24 - On-Treatment Analysis
mmol/L	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Change at Week 12	0.23 ± 4.44	0.45 ± 4.73	0.22 ± 2.70	0.15 ± 2.74
Change at Week 24	0.38 ± 5.24	0.71 ± 4.19	0.52 ± 3.47	0.48 ± 2.53

SecondaryAbsolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis

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

Time frame:: Baseline, Weeks 12 and 24
Reported as:: Mean · units (U)

Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - ITT Analysis
units (U)	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Change at Week 12	-10.0 ± 48.7	-1.3 ± 9.6	0.2 ± 7.9	1.4 ± 11.4
Change at Week 24	-2.2 ± 11.3	-0.8 ± 9.8	2.2 ± 14.8	1.6 ± 11.4

SecondaryAbsolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis

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

Time frame:: Baseline, Weeks 12 and 24
Reported as:: Mean · units (U)

Absolute Change From Baseline in Total Daily Insulin Dose at Weeks 12 and 24 - On-Treatment Analysis
units (U)	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Change at Week 12	-10.0 ± 48.7	-1.3 ± 9.6	0.2 ± 7.9	1.4 ± 11.4
Change at Week 24	-2.2 ± 11.3	-0.8 ± 9.8	1.7 ± 11.7	1.6 ± 11.5

SecondaryAbsolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis

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

Time frame:: Baseline, Weeks 12 and 24
Reported as:: Mean · U/kg

Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - ITT Analysis
U/kg	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Change at Week 12	-0.1 ± 0.5	0.0 ± 0.1	0.0 ± 0.1	0.0 ± 0.1
Change at Week 24	0.0 ± 0.1	0.0 ± 0.1	0.0 ± 0.2	0.0 ± 0.1

SecondaryAbsolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis

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

Time frame:: Baseline, Weeks 12 and 24
Reported as:: Mean · U/kg

Absolute Change From Baseline in Insulin Daily Dose/Kg at Weeks 12 and 24 - On-Treatment Analysis
U/kg	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Change at Week 12	-0.1 ± 0.5	0.0 ± 0.1	0.0 ± 0.1	0.0 ± 0.1
Change at Week 24	0.0 ± 0.1	0.0 ± 0.1	0.0 ± 0.1	0.0 ± 0.1

SecondaryAbsolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis

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.

Time frame:: Baseline, Weeks 12 and 24
Reported as:: Mean · glucose lowering treatments

Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - ITT Analysis
glucose lowering treatments	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Change at Week 12	0 ± 0	0 ± 0	0 ± 0.1	0 ± 0.2
Change at Week 24	0 ± 0	0 ± 0	0 ± 0.3	0 ± 0.2

SecondaryAbsolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis

Time frame:: Baseline, Weeks 12 and 24
Reported as:: Mean · glucose lowering treatments

Absolute Change From Baseline in Number of Glucose-Lowering Treatments at Weeks 12 and 24 - On-Treatment Analysis
glucose lowering treatments	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants
Change at Week 12	0 ± 0	0 ± 0	0 ± 0.1	0 ± 0.2
Change at Week 24	0 ± 0	0 ± 0	0 ± 0.3	0 ± 0.2

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Alirocumab 75 mg Q2W/Up to 150 mg Q2W	0/344 (0%)	31/344 (9%)	17/344 (4.9%)
Placebo Q2W	1/170 (0.6%)	16/170 (9.4%)	9/170 (5.3%)

Most frequent serious events

Showing 10 of 55

Most frequent serious events
Event	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Placebo Q2W
PneumoniaInfections and infestations	1/344	2/170
LymphadenopathyBlood and lymphatic system disorders	0/344	1/170
Acute myocardial infarctionCardiac disorders	0/344	1/170
Angina unstableCardiac disorders	1/344	1/170
Aortic valve stenosisCardiac disorders	0/344	1/170
Ischaemic cardiomyopathyCardiac disorders	0/344	1/170
Myocardial infarctionCardiac disorders	0/344	1/170
DiplopiaEye disorders	0/344	1/170
Gastrointestinal haemorrhageGastrointestinal disorders	0/344	1/170
Intestinal haemorrhageGastrointestinal disorders	0/344	1/170

Most frequent other events

Most frequent other events
Event	Alirocumab 75 mg Q2W/Up to 150 mg Q2W	Placebo Q2W
NasopharyngitisInfections and infestations	17/344	9/170

Baseline characteristics

Baseline population included all randomized participants.

Age, Continuous
Age, Continuous(years)	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants	Total
Mean	54.9 ± 10.1	58.5 ± 7.8	63.9 ± 8.9	64.0 ± 9.4	62.8 ± 9.6

Sex: Female, Male
Sex: Female, Male(Participants)	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants	Total
Female	22	8	133	69	232
Male	29	17	161	78	285

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants	Total
Hispanic or Latino	1	0	13	8	22
Not Hispanic or Latino	50	25	280	138	493
Unknown or Not Reported	0	0	1	1	2

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants	Total
White/Caucasian	50	24	259	135	468
Black	1	0	27	7	35
Asian/Oriental	0	0	7	3	10
American Indian or Alaska Native	0	0	0	0	0
Native Hawaiian or other Pacific Islander	0	0	0	0	0
Other	0	1	1	2	4

Calculated LDL-C in mg/dL
Calculated LDL-C in mg/dL(mg/dL)	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants	Total
Mean	126.4 ± 58.2	110.2 ± 31.2	110.8 ± 36.5	109.6 ± 39.1	112.0 ± 39.8

Calculated LDL-C in mmol/L
Calculated LDL-C in mmol/L(mmol/L)	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T1DM Participants	Placebo Q2W: T1DM Participants	Alirocumab 75 mg Q2W/Up to 150 mg Q2W: T2DM Participants	Placebo Q2W: T2DM Participants	Total
Mean	3.273 ± 1.506	2.853 ± 0.807	2.871 ± 0.944	2.838 ± 1.013	2.900 ± 1.031

Study locations

110 sites

Investigational Site Number 840020
Encino, California 91436, United States
Investigational Site Number 840002
Fresno, California 93720, United States
Investigational Site Number 840029
Oakland, California 94612, United States
Investigational Site Number 840027
Loveland, Colorado 80538, United States
Investigational Site Number 840026
Atlantis, Florida 33462, United States
Investigational Site Number 840006
Bradenton, Florida 33180, United States
Investigational Site Number 840023
Jacksonville, Florida 32205, United States
Investigational Site Number 840028
Palm Harbor, Florida 34684, United States
Investigational Site Number 840022
Ponte Vedra Beach, Florida, United States
Investigational Site Number 840021
Roswell, Georgia 30076, United States
Investigational Site Number 840007
Springfield, Illinois 62704, United States
Investigational Site Number 840011
Indianapolis, Indiana 46260, United States
Investigational Site Number 840015
Valparaiso, Indiana 46383, United States
Investigational Site Number 840010
Des Moines, Iowa 50314, United States
Investigational Site Number 840005
Louisville, Kentucky, United States
Investigational Site Number 840018
Auburn, Maine 04210, United States
Investigational Site Number 840013
Hyattsville, Maryland 20782, United States
Investigational Site Number 840016
Rockville, Maryland 20852, United States
Investigational Site Number 840004
Minneapolis, Minnesota 55416, United States
Investigational Site Number 840012
Jamaica, New York 11432, United States
Investigational Site Number 840014
Maumee, Ohio 43537, United States
Investigational Site Number 840009
Greer, South Carolina 29651, United States
Investigational Site Number 840024
Chattanooga, Tennessee 37404, United States
Investigational Site Number 840001
Austin, Texas 78756, United States
Investigational Site Number 840003
Dallas, Texas 75230, United States
Investigational Site Number 840019
Dallas, Texas 75246, United States
Investigational Site Number 840025
Houston, Texas 77090, United States
Investigational Site Number 840017
Ogden, Utah 84405, United States
Investigational Site Number 840008
Salt Lake City, Utah 84102, United States
Investigational Site Number 040002
Innsbruck, 6020, Austria
Investigational Site Number 040005
Linz, 4021, Austria
Investigational Site Number 040003
Salzburg, 5020, Austria
Investigational Site Number 040004
Salzburg, 5026, Austria
Investigational Site Number 040001
Wien, 1160, Austria
Investigational Site Number 056002
Edegem, 2650, Belgium
Investigational Site Number 056003
Haine-Saint-Paul, 7100, Belgium
Investigational Site Number 056001
Leuven, 3000, Belgium
Investigational Site Number 250-008
Besancon, 25030, France
Investigational Site Number 250-005
Corbeil Essonnes, 91100, France
Investigational Site Number 250-004
La Rochelle Cedex 1, 17019, France
Investigational Site Number 250-003
Le Creusot, 71200, France
Investigational Site Number 250-009
Mulhouse, France
Investigational Site Number 250-002
Nantes cedex 01, 44093, France
Investigational Site Number 250-007
Paris, 75018, France
Investigational Site Number 250-006
Strasbourg Cedex 2, 67098, France
Investigational Site Number 250-001
TOULOUSE Cedex 9, 31059, France
Investigational Site Number 276015
Aschaffenburg, 63739, Germany
Investigational Site Number 276002
Berlin, 10115, Germany
Investigational Site Number 276011
Dortmund, 44137, Germany
Investigational Site Number 276019
Dresden, 01099, Germany
Investigational Site Number 276014
Dresden, 01279, Germany
Investigational Site Number 276009
Dresden, 01307, Germany
Investigational Site Number 276021
Hamburg, 20246, Germany
Investigational Site Number 276018
Hamburg, 22041, Germany
Investigational Site Number 276005
Heidelberg, 69115, Germany
Investigational Site Number 276013
Lüneburg, 21339, Germany
Investigational Site Number 276022
Magdeburg, 39120, Germany
Investigational Site Number 276008
Neumünster, 24534, Germany
Investigational Site Number 276017
Neuwied, 56564, Germany
Investigational Site Number 276004
Oldenburg, 26133, Germany
Investigational Site Number 276003
Pirna, 01796, Germany
Investigational Site Number 276006
Riesa, 01587, Germany
Investigational Site Number 276010
Saarlouis, 66740, Germany
Investigational Site Number 276016
Sulzbach-Rosenberg, 92237, Germany
Investigational Site Number 380004
Catania, 95122, Italy
Investigational Site Number 380003
Catanzaro, Italy
Investigational Site Number 380011
Como, 22100, Italy
Investigational Site Number 380006
Milano, 20132, Italy
Investigational Site Number 380007
Milano, 20162, Italy
Investigational Site Number 380005
Moncalieri, 10024, Italy
Investigational Site Number 380009
Napoli, 80138, Italy
Investigational Site Number 380008
Padova, Italy
Investigational Site Number 380002
Palermo, 90127, Italy
Investigational Site Number 380001
Pisa, 56124, Italy
Investigational Site Number 380010
Roma, 00133, Italy
Investigational Site Number 380012
Verona, 37126, Italy
Investigational Site Number 528002
Apeldoorn, 7334 DZ, Netherlands
Investigational Site Number 528005
Groningen, Netherlands
Investigational Site Number 528003
Hoogeveen, 7909AA, Netherlands
Investigational Site Number 528001
Rotterdam, 3045PM, Netherlands
Investigational Site Number 528004
Utrecht, Netherlands
Investigational Site Number 724007
Badalona, 08915, Spain
Investigational Site Number 724001
Barcelona, 08025, Spain
Investigational Site Number 724006
Ferrol, 15405, Spain
Investigational Site Number 724013
Granada, 18003, Spain
Investigational Site Number 724005
Madrid, 28040, Spain
Investigational Site Number 724004
Madrid, Spain
Investigational Site Number 724011
Majadahonda, 28222, Spain
Investigational Site Number 724008
Málaga, 29010, Spain
Investigational Site Number 724014
Oviedo, 33006, Spain
Investigational Site Number 724009
Palma de Mallorca, 07198, Spain
Investigational Site Number 724002
Pamplona, 31008, Spain
Investigational Site Number 724010
Sant Joan Despí, 08970, Spain
Investigational Site Number 724012
Segovia, Spain
Investigational Site Number 724003
Sevilla, 41071, Spain
Investigational Site Number 756001
Olten, 4600, Switzerland
Investigational Site Number 756003
St. Gallen, 9016, Switzerland
Investigational Site Number 826010
Airdrie, ML60JS, United Kingdom
Investigational Site Number 826011
Bath, BA13NG, United Kingdom
Investigational Site Number 826009
Bournemouth, BH77DW, United Kingdom

Showing the first 100 of 110 sites across 10 countries.

References and documents

Publications

Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3. PubMed 33078867 ↗
Ray KK, Del Prato S, Muller-Wieland D, Cariou B, Colhoun HM, Tinahones FJ, Domenger C, Letierce A, Mandel J, Samuel R, Bujas-Bobanovic M, Leiter LA. Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies. Cardiovasc Diabetol. 2019 Nov 9;18(1):149. doi: 10.1186/s12933-019-0951-9. PubMed 31706300 ↗
Leiter LA, Cariou B, Muller-Wieland D, Colhoun HM, Del Prato S, Tinahones FJ, Ray KK, Bujas-Bobanovic M, Domenger C, Mandel J, Samuel R, Henry RR. Efficacy and safety of alirocumab in insulin-treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM-INSULIN randomized trial. Diabetes Obes Metab. 2017 Dec;19(12):1781-1792. doi: 10.1111/dom.13114. Epub 2017 Oct 10. PubMed 28905478 ↗

Study documents

Study protocol · Jul 8, 2015
Statistical analysis plan · Mar 6, 2017

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 17, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02585778
Lead sponsor: Sanofi
Collaborators: Regeneron Pharmaceuticals
Responsible party: Sponsor
First posted: Oct 23, 2015
Start date: Oct 23, 2015
Primary completion: Apr 3, 2017
Completion: Apr 3, 2017
Results posted: May 17, 2018
Last update: May 17, 2018

Study contacts

Clinical Sciences & Operations

study director · Sanofi

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Apr 2018. You cannot join it, but the record below documents what was studied.

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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)

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