For adults with type 2 diabetes (T2D) and established CVD,
for the composite primary endpoint
After 2 years, Ozempic® (semaglutide) significantly lowered the risk of MACE (nonfatal MI, nonfatal stroke, or CV death)1,a
aResults apply to Ozempic® 0.5 mg and 1 mg plus standard of care vs placebo plus standard of care.
CV=cardiovascular; CVD=cardiovascular disease; MACE=major adverse cardiovascular event; MI=myocardial infarction.
Composite MACE endpoint: CV death, nonfatal MI, or nonfatal stroke.1
Time to first confirmed major adverse CV event (MACE)1,2,a
NNT 45
Number needed to
treat to prevent
1 MACE
(2 years)2,3,c
bStandards of care included, but were not limited to, oral antidiabetic treatments, insulin, antihypertensives, diuretics, lipid-lowering therapies, and antithrombotic medications.2
cEstimated cumulative risk of MACE at Week 104 was 6.2% with Ozempic® 0.5 mg and 1 mg and 8.4% with placebo.4
ARR=absolute risk reduction; CI=confidence interval; CV=cardiovascular; CVD=cardiovascular disease; MACE=major adverse cardiovascular event; MI=myocardial infarction; NNT=number needed to treat; RRR=relative risk reduction; SOC=standard of care; T2D=type 2 diabetes.
SUSTAIN 6: A 2-year cardiovascular outcomes trial (CVOT) for Ozempic®1,2
A 104-week, multicenter, multinational, placebo-controlled, double-blind CVOT in 3297 adult patients with inadequately controlled type 2 diabetes and atherosclerotic cardiovascular disease. Patients had a mean duration of diabetes of 13.9 years and a mean baseline A1C of 8.7%, and 58% were taking insulin.
Additional SUSTAIN 6 study information
dFor the primary analysis, a Cox proportional-hazards model was used to test for noninferiority of Ozempic® to placebo for time to first MACE using a risk margin of 1.3.1,2
eEstablished CV disease (previous CV, cerebrovascular, or peripheral vascular disease) or chronic heart failure (New York Heart Association class II or III) or chronic kidney disease stage 3 or higher.1,2
fDefined as persistent microalbuminuria (30-299 mg/g) or proteinuria, hypertension and left ventricular hypertrophy by electrocardiogram or imaging, left ventricular systolic or diastolic dysfunction by imaging, or ankle/brachial index <0.9 of those in the trial.3
gTrial consisted of 104 weeks of treatment (including a 4- to 8-week dose escalation period), with a subsequent 5-week follow-up period.1,2
CV=cardiovascular; CVD=cardiovascular disease; MACE=major adverse cardiovascular event; MI=myocardial infarction; OAD=oral antidiabetic drug.
83% of patients had established CVD2,h,i
Patient characteristics (n=3297)1,2
hPrior CV disease was defined as age ≥60 years with at least 1 CV risk factor (persistent microalbuminuria [30-299 mg/g] or proteinuria, hypertension and left ventricular hypertrophy by electrocardiogram or imaging, left ventricular systolic or diastolic dysfunction by imaging, or ankle/brachial index <0.9) or age ≥50 years with established CVD (previous CV, cerebrovascular, or peripheral vascular disease; chronic heart failure [New York Heart Association class II of III); or chronic kidney disease of stage 3 or higher).2,3
iIn total, 1940 patients (58.8%) had established CV disease without CKD, 353 (10.7%) had CKD only, and 442 (13.4%) had both CV disease and CKD; 562 patients (17%) had CV risk factors without established CV disease or CKD. In the trial, 453 patients (13.7%) had peripheral artery disease.1
BMI=body mass index; CKD=chronic kidney disease; CV=cardiovascular; CVD= cardiovascular disease
98% of patients were receiving CV medications at baseline2,3
Summary of CV medication usage at baseline (n=3297)3
History of CVD at screening (n=3297)1,3,j
jHistory at baseline among subjects enrolled in the trial (Ozempic® and placebo groups).2
kComprised of asymptomatic (silent) cardiac ischemia (8.6%), stable angina pectoris (14.6%), unstable angina (7.3%), non-ST-segment elevation (11%), ST-segment elevation MI (2.1%) and unknown (6.7%).3,4
lThe ACC defines ASCVD as: a history of an acute coronary syndrome or myocardial infarction, stable or unstable angina, coronary heart disease with or without revascularization, other arterial revascularization, stroke, or peripheral artery disease assumed to be atherosclerotic in origin.5
ACC=American College of Cardiology; ACE=angiotensin-converting enzyme; ASCVD=atherosclerotic cardiovascular disease; PAD=peripheral artery disease.
Ozempic® significantly reduced risk of MACE, driven by rate of nonfatal stroke1,2
For adults with T2D and established CVD, for the composite primary endpoint after 2 years vs placebo, when both were added to SOC1,m
Composite MACE endpoint: CV death, nonfatal MI,
or nonfatal stroke1,2
39%
significant
reduction
in rate of
nonfatal stroke
drove the MACE
reduction1,2,r
This study was not powered to detect a difference in the individual endpoints of the composite MACE. Absolute rates for the combined endpoint of “fatal or nonfatal stroke”: 1.8% (n=30 of 1648) with Ozempic® and 2.8% (n=46 of 1649) with placebo. HR, 0.65 (95% CI, 0.41-1.03); P=NS. There was no significant change in the rate of nonfatal MI or CV death.
Overall MACE occurred in 108 patients of 1648 (6.6%) on Ozempic® (0.5 mg and 1 mg) and 146 patients of 1649 (8.9%) on placebo (HR, 0.74 [95% CI, 0.58-0.95] P<0.001 for noninferiority, P=0.02 for superiority, not prespecified); nonfatal stroke occurred in 27 patients (1.6%) on Ozempic® and 44 patients (2.7%) on placebo; nonfatal Ml occurred in 47 patients (2.9%) on Ozempic® and 64 patients (3.9%) on placebo; CV death occurred in 44 patients (2.7%) on Ozempic® and 46 patients (2.8%) on placebo.1,2
mStandards of care included, but was not limited to, oral antidiabetic treatments, insulin, antihypertensives, diuretics, lipid-lowering therapies, and antithrombotic medications.2
nResults apply to Ozempic® 0.5 mg and 1 mg plus standard of care vs placebo plus standard of care.
oHazard ratio vs placebo (95% CI). Median study observation time of 2.1 years. Cox proportional-hazards models with treatment as fixed factor and stratified by evidence of cardiovascular disease, insulin treatment, and renal impairment. P values other than for the primary hypothesis (noninferiority) are unadjusted for multiplicity and test null hypotheses of no difference.1,2
pP value is not adjusted for multiplicity and tests null hypotheses of no difference (post hoc).2
qThe primary endpoint in the SUSTAIN 6 CVOT was time to first occurrence of a 3-part composite MACE that included CV death, nonfatal MI, or nonfatal stroke.1
ARR=absolute risk reduction; CI=confidence interval; CV=cardiovascular; CVD=cardiovascular disease; CVOT=cardiovascular outcomes trial; HR=hazard ratio; MACE=major adverse cardiovascular event; MI=myocardial infarction; NNT=number needed to treat; NS=notsignificant; RRR=relative risk reduction; SOC=standard of care; T2D=type 2 diabetes.
WHAT A CARDIOLOGIST IS SAYING ABOUT OZEMPIC®
"As a cardiologist, you either prescribe or recommend to your colleagues a medication with proven CVD benefit and label indication for patients with T2D and established CVD. So you have to know about Ozempic®."
DR JOSHUA STOLKER | CARDIOLOGIST
Ozempic® has once-weekly dosing1
More ways to help your patients with T2D
Important Safety Information for Ozempic® (semaglutide) injection
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Ozempic® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- Ozempic® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Ozempic® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Ozempic®
Indications and Usage
Ozempic® (semaglutide) injection 0.5 mg, 1 mg, or 2 mg is indicated:
- as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
- to reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, or nonfatal stroke) in adults with type 2 diabetes and established CV disease
- to reduce the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in adults with type 2 diabetes and chronic kidney disease
Important Safety Information cont.
Contraindications
- Ozempic® is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with a hypersensitivity reaction to semaglutide or to any of the excipients in Ozempic®. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with Ozempic®
Warnings and Precautions
- Risk of Thyroid C-Cell Tumors: Patients should be further evaluated if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide. Observe patients carefully for signs and symptoms of pancreatitis (persistent severe abdominal pain, sometimes radiating to the back with or without vomiting). If pancreatitis is suspected, discontinue Ozempic® and initiate appropriate management
- Diabetic Retinopathy Complications: In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with Ozempic® (3.0%) compared with placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline than among patients without a known history of diabetic retinopathy.
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy - Never Share an Ozempic® Pen Between Patients: Ozempic® pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens
- Hypoglycemia: Patients receiving Ozempic® in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia
- Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Ozempic® that could lead to volume depletion, especially during dosage initiation and escalation
- Severe Gastrointestinal Adverse Reactions: Use of Ozempic® has been associated with gastrointestinal adverse reactions, sometimes severe. In Ozempic® clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving Ozempic® (0.5 mg 0.4%, 1 mg 0.8%) than placebo (0%). Ozempic® is not recommended in patients with severe gastroparesis
- Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with Ozempic®. If hypersensitivity reactions occur, discontinue use of Ozempic®; treat promptly per standard of care, and monitor until signs and symptoms resolve. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials, cholelithiasis was reported in 1.5% and 0.4% of patients treated with Ozempic® 0.5 mg and 1 mg, respectively, and not reported in placebo-treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: Ozempic® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Ozempic®
Adverse Reactions
- The most common adverse reactions, reported in ≥5% of patients treated with Ozempic® are nausea, vomiting, diarrhea, abdominal pain, and constipation
Drug Interactions
- When initiating Ozempic®, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
- Ozempic® causes a delay of gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications, so caution should be exercised
Use in Specific Populations
- There are limited data with semaglutide use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. Discontinue Ozempic® in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide
Please click here for Ozempic® Prescribing Information, including Boxed Warning.
References:
- Ozempic® [package insert]. Plainsboro, NJ: Novo Nordisk Inc.
- Marso SP, Bain SC, Consoli A, et al.; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834-1844
- Marso SP, Bain SC, Consoli A, et al.; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (supplemental appendix). N Engl J Med. 2016;375:1834-1844.
- Data on file. Novo Nordisk Inc.; Plainsboro, NJ.
- Das SR, Everett BM, Birtcher KK, et al. 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2020;76(9):1117-1145.