Proven to help prevent life-threatening CV events

SELECT, a landmark study: The largest CVOT ever completed for patients with established CVD and obesity^1-3

MACE risk reduction was evaluated on top of CV standard of care¹*

Patient population

17,604

patients without diabetes

17,061 (~97%) completed the trial^1,2†

Patient enrollment: October 2018-March 2021It took Novo Nordisk 4.5 years to conduct this trial

Key Inclusion Criteria

Adults: ≥45 years
BMI: ≥27 kg/m²

Established CVD:
• Prior MI
• Prior stroke
• PAD

Treatment arms^1,2

Event-driven superiority trial: 1,225 accrued events

Median duration of follow-up: 41.8 months

Primary composite end point

Time from randomized to
first occurrence of MACE^1,2

Time from randomization to first occurrence of MACE

Assessed regardless of change in weight

What could life-saving outcomes mean for your patients?

CV standard-of-care treatments at baseline included^1,2‡:

Medication Class

Lipid-lowering therapy

Platelet aggregation inhibitors

Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers

Beta-blockers

Percentage of Patients (N=17,604)

90%

86%

74%

70%

Throughout the trial, CV therapies could be adjusted at investigator discretion according to current standard of care¹

Baseline cardiometabolic parameters¹

Heart rate

A1c

Systolic blood pressure

Diastolic blood pressure

Triglycerides

Total cholesterol

LDL cholesterol

HDL cholesterol

Wegovy^® injection (n=8,803)

69 bpm

5.8%

131 mm Hg

79 mm Hg

138.6 mg/dL

155.5 mg/dL

78.5 mg/dL

44.1 mg/dL

Placebo 
(n=8,801)

69 bpm

5.8%

131 mm Hg

79 mm Hg

139.5 mg/dL

156 mg/dL

78.5 mg/dL

44.2 mg/dL

*Standard of care included CV risk-factor management and individualized healthy lifestyle counseling (including diet and physical activity).
 ^†Defined as having died or attended the final trial visit. 
^‡Not a comprehensive list. 
ARR, absolute risk reduction; BMI, body mass index; CV, cardiovascular; CVD, cardiovascular disease; CVOT, cardiovascular outcomes trial; MACE, major adverse cardiovascular events; Ml, myocardial infarction; PAD, peripheral arterial disease; SOC, standard of care.

SELECT: In adults with established CVD and either obesity or overweight, without diabetes, when added to CV standard of care,

Wegovy^® is proven to help prevent life-threatening CV events^1-3

Cardiovascular disease is the #1 cause of death for adults with obesity⁴

Primary composite end point: Time to first occurrence of MACE (CV death, non-fatal MI, or non-fatal stroke)^1,2

20% RRR of MACE when added to CV SOC 

1.5% ARR

6.5% (n=569 of 8,803) of patients on Wegovy^® pen experienced an event compared with 8.0% (n=701 of 8,801) with placebo. 
HR, 0.80 (95% CI, 0.72-0.90).

The exact mechanism of cardiovascular risk reduction of Wegovy^® has not been established.¹

The results from SELECT are based on a trial with injectable Wegovy^® 2.4 mg

RRR of MACE
 when added to CV SOC^1,2

1.5% ARR^5§

With Wegovy^®, the reduction of MACE was not impacted by age, sex, race, ethnicity, BMI at baseline, or level of renal function impairment.¹

SELECT^1,2: Event-driven CVOT of 17,604 adults with obesity or overweight and established CVD (prior MI, prior stroke, or PAD) assessing superiority of once-weekly injectable Wegovy^® 2.4 mg vs placebo (1:1 randomization) for time to first MACE. Both groups received standard of care for CV risk reduction. Patients with diabetes were excluded. Click to see full study design below.  

^§1.5% ARR at 40 months (mean duration of follow-up).⁵
CI, confidence interval; RRR, relative risk reduction.

You can prescribe appropriate patients looking for MACE risk reduction the Wegovy^® pen or pill

Treatment effect for MACE and other events in SELECT¹

The effects of semaglutide were directionally similar across end points¹

Treatment effect for MACE and other events in SELECT

Wegovy^® is not indicated to reduce the risk of heart failure events.

CV death occurred in 2.5% (223/8,803) of patients on Wegovy^® and 3.0% (262/8,801) of patients on placebo¹
All-cause death occurred in 4.3% (375/8,803) of patients on Wegovy^® and 5.2% (458/8,801) of patients on placebo¹
Fatal or non-fatal MI occurred in 2.8% (243/8,803) of patients on Wegovy^® and 3.8% (334/8,801) of patients on placebo¹
Fatal or non-fatal stroke occurred in 1.8% (160/8,803) of patients on Wegovy^® and 2.0% (178/8,801) of patients on placebo¹
Hospitalization for heart failure or urgent heart failure visits occurred in 1.1% (97/8,803) of patients on Wegovy^® and 1.4% (122/8,801) of patients on placebo¹

In the same study,

Patients taking Wegovy^® experienced improvements across most cardiometabolic risk factors¹

Supportive secondary end points: Change from baseline to week 104 in:

Wegovy^® is not indicated to treat hypertension, type 2 diabetes, or dyslipidemia.

Supportive secondary end points were not included in the statistical testing hierarchy and, as such, not controlled for multiplicity.

A1c, glycated hemoglobin; bpm, beats per minute; HDL, high-density lipoprotein; LDL, low-density lipoprotein.

SELECT Post Hoc Analysis

Early reduction in MACE was observed at 3 months with Wegovy^® before clinically meaningful changes in body weight were seen⁵

Primary composite end point: Time to first occurrence of MACE (CV death, non-fatal MI, or non-fatal stroke)^1,5

At week 12, estimated mean change in body weight from baseline was -4.1% in the Wegovy^® arm and -0.6% in the placebo arm.⁵

Limitations:

This post hoc analysis is hypothesis generating only; the clinical validity of these results cannot be determined
SELECT was not powered for this analysis; Novo Nordisk was responsible for data analysis
Further work addressing the mechanisms by which semaglutide produces these early clinical benefits would be of value³

Time to first MACE: Incidence over time⁵

Number of events

Month

Wegovy^®

Placebo

0-3

36

58

The exact mechanism of cardiovascular risk reduction has not been established.¹ 
Clinically meaningful weight loss is generally defined as ≥5% weight loss from baseline.⁶

Please click here for full SELECT study design.

Please first review the SELECT data before assessing the SCORE real-world data.

Randomized clinical trials (RCTs)^7,8

Evaluate the safety and efficacy of a treatment in specific populations under controlled conditions
Prospective designs with prespecified, well-defined inclusion/exclusion criteria, outcomes, and end points
Patients are randomly assigned to treatment or comparator

Limitations:

Tightly controlled conditions and inclusion/exclusion criteria of RCTs may limit generalizability to real-world conditions or clinical populations
Can be expensive and time-consuming

Randomized clinical trials are designed to show causality^7,8

Real-world evidence (RWE)^8,9

Use data from routine clinical practice
Capture outcomes across broad patient populations
Offer insight into how treatments perform outside of a controlled clinical trial setting
Should be viewed as complementary to clinical trial data

Limitations:

Susceptible to bias and confounding due to factors such as lack of randomization, missing or duplicative data, coding inaccuracies, and data variability reflecting routine clinical practice

Real-world studies evaluate associations and cannot determine causality^8,9

SCORE: The largest real-world CV outcomes study assessing the effectiveness of Wegovy^® in adults with established CVD and overweight or obesity^{10 ‖}

Patient population¹⁰

27,963

patients

Baseline period: 12 months prior to index date¹¹

Key Inclusion Criteria^10¶

Adults: ≥45 years
Overweight or obesity
(BMI: ≥27 kg/m²)

Established CVD:
• Prior MI
• Ischemic stroke
• PAD

No prior history of diabetes

Treatment arms¹⁰

End point assessed¹⁰

MACE-3

CV Death** Non-Fatal MI Non-Fatal Stroke

Patients were followed until the
earliest instance of¹⁰:

• The earliest instance of the end of continuous enrollment or of data availability
• The initiation of a (non-semaglutide) GLP-1 or GLP-1/GIP receptor agonist
• A bariatric surgical procedure
• Death

This study used the Komodo research database, which includes administrative medical and pharmacy claims linked with clinical and laboratory measurements for patients in the US during January 1, 2016-December 31, 2023.

Index date definition: Wegovy^® injection users: The initiation date of Wegovy^® in a pharmacy claim on or after June 4, 2021. Non-users: A randomly selected date with 21 pharmacy claim(s) on or after June 4, 2021.

Patients were followed until the earliest instance of the end of continuous enrollment or of data availability, initiation of a (non-semaglutide) GLP-1 or GIP/GLP-1 receptor agonist, bariatric surgical procedure, or death.

^∥As of March 24, 2025.
^¶Inclusion criteria and end points were identified by ICD-10 codes, procedural codes, or recorded measurements (BMI).
^#A non-parsimonious PS model was used to alleviate the effect of potential confounding on systematic differences in patient characteristics based on treatment exposure. Over 50 variables were matched, including: age, gender, race/ethnicity, region, insurance type, index year, duration between the eligibility date and index date, BMI, smoking history, comorbidities, procedures, medication use, and health care resource utilization. 
**CV death: Death within ≤30 days of a CV event.  
GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1; PS, propensity score.

Incidence of MACE with Wegovy^® in a real-world study

Outcome: Time to first occurrence of MACE-3 (CV death, non-fatal MI, non-fatal stroke)¹⁰

Results should be interpreted in the context of the limitations of this study.

In Wegovy^® pen users vs non-users^3,10

Mean duration of follow-up: 7.1 months
with Wegovy^® users; 6.4 months with
non-users

Limitations: Despite robust PS matching and multiple sensitivity analyses, the potential for residual unmeasured confounding exists. The approval of Wegovy^® in 2021 resulted in a relatively short duration of follow-up, limiting assessment of long-term outcomes. Requiring 12 months of continuous coverage before the index date may exclude patients with intermittent insurance coverage or those from underserved populations, limiting generalizability.¹⁰

^††Event rates per person-year: 41 events over 5,519 person-years for Wegovy^® injection users, 128 events over 9,859 person-years for non-users. 
^‡‡The relative risk reduction is approximated by 1-hazard ratio. 
^§§ARR represents the difference in event rates per person-year in semaglutide users vs non-users.

Study designs

SELECT^1,2: A multi-national, double-blind, placebo-controlled, event-driven CV outcomes trial of 17,604 adults with a BMI ≥27 kg/m² and established CVD (prior MI, prior stroke, or PAD) assessing superiority of once-weekly injectable Wegovy^® 2.4 mg vs placebo (1:1 randomization, with a 16-week dose escalation) for time to first MACE. Both groups received current standard of care, including CV risk factor management and individualized healthy lifestyle counseling (including diet and physical activity); concomitant CV therapies could be adjusted, at the discretion of the investigator, to ensure participants were treated according to the current standard of care for patients with established CVD. Patients with a history of type 1 or type 2 diabetes were excluded. Median duration of follow-up was 41.8 months.

Primary composite end point²:

Time from randomization to first occurrence of a 3-part composite MACE, defined as CV death, non-fatal MI, or non-fatal stroke

Key secondary end points²:

Time from randomization to first occurrence of:

Cardiovascular death
All-cause death

Other secondary end points²:

Time from randomization to first occurrence of:

Fatal or non-fatal myocardial infarction
Fatal or non-fatal stroke

Relevant supportive secondary end points²:

Change in body weight from baseline to week 104
Change in waist circumference from baseline to week 104
Change in systolic blood pressure from baseline to week 104
Change in diastolic blood pressure from baseline to week 104
Change in heart rate from baseline to week 104
Change in A1c from baseline to week 104
Change in lipids^∥∥ from baseline to week 104

^∥∥∥∥LDL, HDL, triglycerides, and total cholesterol.

SCORE^3,10: A retrospective observational study using the Komodo Research Dataset (EHR linked to medical and pharmacy claims) of 27,963 US adults with a BMI ≥27 kg/m² and established CVD (prior MI, prior stroke, or PAD) comparing the incidence of MACE-3 (CV death, non-fatal MI, or non-fatal stroke) in Wegovy^® injection users vs non-users without diabetes. Full study period was from January 1, 2016, to December 31, 2023. Index date was defined as first Wegovy^® claim or randomly selected pharmacy claim on or after June 4, 2021, for Wegovy^® injection users and non-users, respectively. Baseline period was 12 months prior to the index date. Wegovy^® injection users and non-users were matched using a non-parsimonious PS model to alleviate the effect of potential confounding on systematic differences in patient characteristics. Over 50 variables were matched, including age, gender, race/ethnicity, region, insurance type, index year, duration between the eligibility date and index date, BMI, smoking history, comorbidities, procedures, medication use, and health care resource utilization.

End point:

Time to first occurrence of MACE-3 (CV death, non-fatal MI, or non-fatal stroke)