aWeight change was secondary endpoint in clinical trials.
bComposite MACE endpoint included: CV death, nonfatal Ml, or nonfatal stroke.1 Results apply to Ozempic® 0.5 mg and 1 mg plus standard of care vs placebo plus standard of care. Overall MACE occurred in 108 patients of 1648 (6.6%) on Ozempic® and 146 patients of 1649 (8.9%) on placebo (HR, 0.74 [95% Cl, 0.58-0.95]; P<0.001 for noninferiority vs placebo, P=0.02 for superiority, not prespecified.)
Efficacy data from 4 clinical trials
In adult patients with T2D on metformin
Primary endpoint: Mean change in A1C from baseline at Week 402,3
SUSTAIN 7: vs Trulicity®2
In insulin-naïve adult patients with T2D on metformin ± SU
Primary endpoint: Mean change in A1C from baseline at Week 301,3,4
SUSTAIN 4: vs study-titrated Lantus®
In adult patients with T2D on basal insulin ± metformin
Primary endpoint: Mean change in A1C from baseline at Week 301,3,5
SUSTAIN 5: Add-on to basal insulin
In adult patients with T2D on metformin ± SU
Primary endpoint: Mean change in A1C from baseline at Week 401,6
SUSTAIN FORTE: Ozempic® 1 mg vs 2 mg
ETD=estimated treatment difference; CI=confidence interval; MET=metformin; SU=sulfonylurea.
OZEMPIC® IS NOT INDICATED FOR WEIGHT LOSS
In adult patients with T2D on metformin
Secondary endpoint: Mean change in body weight from baseline to Week 402,3
SUSTAIN 7: vs Trulicity®
Mean baseline: 209 lb2
In insulin-naïve adult patients with T2D on metformin ± SU
Secondary endpoint: Mean change in body weight from baseline to Week 301,3,4
SUSTAIN 4: vs study-titrated Lantus®
Mean baseline: 206 lb1
In adult patients with T2D on basal insulin ± metformin
Secondary endpoint: Mean change in body weight from baseline at Week 301,3,5
SUSTAIN 5: Add-on to basal insulin
Mean baseline: 202 lb5
In adults with T2D on metformin ± SU
Secondary endpoint: Mean change in body weight from baseline at Week 401,3,6
SUSTAIN FORTE: Ozempic® 1 mg vs 2 mg
Mean baseline: 219 lb6
Results for all trials were only designed to detect a difference in weight from baseline to Week 40 for SUSTAIN 7 and SUSTAIN FORTE and from baseline to Week 30 for SUSTAIN 4 and SUSTAIN 5.
ETD=estimated treatment difference; CI=confidence interval; SU=sulfonylurea.
SUSTAIN 7:
A 40-week, randomized, open-label, active-controlled trial in 1201 adult patients with type 2 diabetes on metformin comparing Ozempic® 0.5 mg with Trulicity® 0.75 mg and Ozempic® 1 mg with Trulicity® 1.5 mg.2
SUSTAIN 4:
A 30-week, randomized, open-label, active-controlled, treat-to-target trial in 1089 insulin-naïve adult patients with type 2 diabetes on metformin with or without sulfonylurea, comparing Ozempic® 0.5 mg and Ozempic® 1 mg with Lantus®.1,4
SUSTAIN 5:
A 30-week, randomized, double-blind, placebo-controlled, parallel-group trial in 397 adult patients with type 2 diabetes, evaluating the addition of Ozempic® 0.5 mg and Ozempic® 1 mg to basal insulin ± metformin.1,5 Patients with A1C ≤8% at screening had their background basal insulin dose reduced by 20% at the start of the trial to limit potential risk of hypoglycemia.
SUSTAIN FORTE:
A 40-week, randomized, active-controlled trial in 961 adult patients with type 2 diabetes on metformin with or without a sulfonylurea, comparing Ozempic® 1 mg with Ozempic® 2 mg.1,6
Ozempic® has proven CV risk reduction in patients with T2D and established CVD1
See data from a 2-year cardiovascular outcomes trial with a composite primary MACE endpoint of CV death, nonfatal MI, or nonfatal stroke.
The experts are talking about Ozempic®
Hear from diabetes experts across a range of specializations in the Ozempic® video collection.
The Coffee with Coco series
Time for a coffee break? Join Nurse Practitioner Lisa Coco as she talks T2D with other leading experts in diabetes care.
Ozempic® vs Trulicity®
Learn about the results of a head-to-head trial of 2 once-weekly GLP-1 RA therapies from one of the primary investigators.
Ozempic® as the first injectable
Hear an MD and an NP on why they consider a GLP-1 RA therapy as the first injectable for appropriate patients.
More ways to help your patients with T2D
STUDY DESIGNS
SUSTAIN 7: Head-to-head vs Trulicity® (dulaglutide)2
Study design: 40-week, multinational, multicenter, randomized, open-label, 4-armed, pairwise, active-controlled, parallel-group trial to compare the efficacy and safety of Ozempic® vs dulaglutide.
Patients: A total of 1201 adult patients with type 2 diabetes inadequately controlled on metformin were randomized to receive Ozempic® 0.5 mg (n=301), Ozempic® 1 mg (n=300), dulaglutide 0.75 mg (n=299), or dulaglutide 1.5 mg (n=299) once weekly.
Primary endpoint: Mean change in A1C from baseline at Week 40.
Secondary endpoints: Mean change in body weight from baseline at Week 40; proportion of patients achieving A1C <7% at Week 40.
SUSTAIN 4: Head-to-head vs Lantus® (insulin glargine U-100)4
Study design: 30-week, randomized, open-label, active-controlled, parallel-group, multinational, multicenter trial to compare the efficacy and safety of Ozempic® vs insulin glargine U‑100.
Patients: A total of 1089 insulin-naïve adult patients with type 2 diabetes inadequately controlled on metformin alone (48%) or in combination with a sulfonylurea (51%) were randomized to receive once-weekly Ozempic® 0.5 mg (n=362), once-weekly Ozempic® 1 mg (n=360), or once-daily insulin glargine U-100 (n=360). Patients assigned to insulin glargine had a baseline mean A1C of 8.1% and were started on a dose of 10 units once daily. Insulin glargine dose adjustments occurred throughout the trial period based on self-measured fasting plasma glucose before breakfast, targeting 71 to <100 mg/dL. In addition, investigators could titrate insulin glargine based on their discretion between study visits. Twenty-six percent of patients had been titrated to goal by the primary endpoint at Week 30, at which time the mean daily insulin dose was 29 units per day.
Primary endpoint: Mean change in A1C from baseline at Week 30.
Secondary endpoints: Mean change in body weight from baseline at Week 30; proportion of patients achieving A1C <7% at Week 30.
SUSTAIN 5: As an add-on to basal insulin vs placebo5
Study design: 30-week, randomized, double-blind, placebo-controlled, parallel-group, multinational, multicenter trial to compare the efficacy and safety of Ozempic® in combination with basal insulin vs volume-matched placebo in combination with basal insulin.
Patients: A total of 397 adult patients inadequately controlled on basal insulin with or without metformin were randomized to once-weekly Ozempic® 0.5 mg (n=132), Ozempic® 1 mg (n=131), or placebo (n=133). Randomization was stratified according to A1C at screening. Patients with A1C ≤8% at screening reduced the insulin dose by 20% at the start of the trial to reduce the risk of hypoglycemia.
Primary endpoint: Mean change in A1C from baseline at Week 30.
Secondary endpoints: Mean change in body weight from baseline at Week 30; proportion of patients achieving A1C <7% at Week 30; change in mean fasting plasma glucose (FPG) at Week 30.
SUSTAIN FORTE: Ozempic® 1 mg vs 2 mg6
Study design: 40-week, randomized, active-controlled, parallel-group, double-blind, phase 3B efficacy and safety trial of Ozempic® 2 mg vs Ozempic® 1 mg in patients with type 2 diabetes in need of treatment intensification.
Patients: A total of 961 adult patients with inadequately controlled type 2 diabetes (A1C 8.0%-10.0%) on metformin with or without a sulfonylurea were randomized 1:1 to 2.0 mg (n=480) or 1.0 mg (n=481) of once-weekly Ozempic®.
Primary endpoint: Mean change in A1C from baseline at Week 40.
Secondary endpoints: Mean change in body weight from baseline at Week 40; proportion of patients achieving A1C <7.0% at Week 40.
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 Limitations of Use
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 mellitus and to reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, or nonfatal stroke) in adults with type 2 diabetes mellitus and established CV disease.
- Ozempic® has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
- Ozempic® is not indicated for use in patients with type 1 diabetes mellitus.
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 referred to an endocrinologist for further evaluation if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging.
- Pancreatitis: Acute and chronic pancreatitis have been reported in clinical studies. 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® promptly, and if pancreatitis is confirmed, do not restart.
- 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 (eg, 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: There have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis, in patients treated with GLP-1 receptor agonists. Some of these events have been reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Monitor renal function when initiating or escalating doses of Ozempic® in patients reporting severe adverse gastrointestinal reactions.
- Hypersensitivity: Serious hypersensitivity reactions (eg, 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.
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.; March 2022.
- Pratley RE, Aroda VR, Lingvay I, et al, on behalf of the SUSTAIN 7 investigators. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6(4):275-286.
- Data on file. Novo Nordisk Inc., Plainsboro, NJ.
- Aroda VR, Bain SC, Cariou B, et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naïve patients with type 2 diabetes (SUSTAIN 4): a randomized, open-label, parallel-group, multicenter, multinational, phase 3a trial. Lancet Diabetes Endocrinol. 2017:5(5):355-366.
- Rodbard HW, Lingvay I, Reed J, et al. Semaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): a randomised, controlled trial. J Clin Endocrinol Metab. 2018;103(6):2291-2301.
- Frías JP, Auerbach P, Bajaj HS, et al. Efficacy and safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial. Lancet Diabetes Endocrinol. 2021;9(9):563-574. doi: 10.1016/S2213-8587(21)00174-1.