Ozempic® (semaglutide) injection—compelling weight loss across doses1
Ozempic® is not indicated for weight loss.
SUSTAIN 7:
vs Trulicity®
In adult patients with type 2
diabetes on metformin
Secondary endpoint: mean change in body
weight from baseline to Week 402,3
Mean baseline: 209 lb
SUSTAIN FORTE:
Ozempic® 1 mg vs 2 mg
In adult patients with type 2 diabetes
on metformin ± sulfonylurea
Secondary endpoint: mean
change in body weight from
baseline to Week 401,4
Mean baseline: 219 lb
Results for SUSTAIN 7 and SUSTAIN FORTE are based on sensitivity analyses of retrieved dropout population. SUSTAIN 7 and SUSTAIN FORTE were only designed to detect a difference in weight from baseline to Week 40.
The estimated treatment difference was from baseline to Week 40 vs Trulicity® in SUSTAIN 7 and vs Ozempic® 1 mg in SUSTAIN FORTE.
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 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.4
Cl=confidence interval; ETD=estimated treatment difference; NS=not significant.
Adverse events ≥5% in SUSTAIN 7
AEs occurring in ≥5% of participants treated with Ozempic® in SUSTAIN 72
SUSTAIN 7 was not designed to evaluate relative safety between Ozempic® and Trulicity®
AE=adverse event; GI=gastrointestinal.
- In placebo-controlled trials, the most common adverse reactions reported in ≥5% of patients treated with Ozempic® are nausea, vomiting, diarrhea, abdominal pain, and constipation.1
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Comparator AE rates are not an adequate basis for comparison of safety between products.
Adverse events ≥5% in SUSTAIN FORTE
AEs occurring in ≥5% of patients receiving Ozempic® 1 mg and 2 mg in SUSTAIN FORTE4
- In placebo-controlled trials, the most common adverse reactions reported in ≥5% of patients treated with Ozempic® are nausea, vomiting, diarrhea, abdominal pain, and constipation.1
- No new safety signals were identified. Gastrointestinal adverse reactions occurred more frequently among patients receiving Ozempic® 2 mg (34.0%) vs Ozempic® 1 mg (30.8%).4
- Incidence of severe hypoglycemia (level 3) was less than 1% for Ozempic® 1 mg and Ozempic® 2 mg in the SUSTAIN FORTE trial.4
SUSTAIN 4:
vs study-titrated Lantus®
In insulin-naïve patients with type 2
diabetes on metformin ± sulfonylurea
Secondary endpoint:
mean change in body weight
from baseline to Week 301,5
Mean baseline: 206 lb
SUSTAIN FORTE:
Ozempic® 1 mg vs 2 mg
In adult patients with type 2 diabetes
on metformin ± sulfonylurea
Secondary endpoint:
mean change in body weight
from baseline to Week 401,4
Mean baseline: 219 lb
Results based on sensitivity analyses of retrieved dropout population. SUSTAIN 4 and SUSTAIN FORTE were only powered to detect differences in A1C from baseline to Week 30 and Week 40, respectively.
The estimated treatment difference was from baseline to Week 30 for SUSTAIN 4 and from baseline to Week 40 for SUSTAIN FORTE.
SUSTAIN 4: Results are from a 30-week, randomized, open-label, active-controlled trial in 1089 insulin-naïve adult patients on metformin ± sulfonylurea with type 2 diabetes comparing Ozempic® 0.5 mg and Ozempic® 1 mg with Lantus®.5
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.4
Cl=confidence interval; ETD=estimated treatment difference; NS=not significant.
AEs occurring in ≥5% of participants treated with Ozempic® in SUSTAIN 45
SUSTAIN 4 was not designed to evaluate relative safety between Ozempic® and Lantus®
AE=adverse event; GI=gastrointestinal.
- In placebo-controlled trials, the most common adverse reactions reported in ≥5% of patients treated with Ozempic® are nausea, vomiting, diarrhea, abdominal pain, and constipation.1
- Because clinical trials are conducted under widely varying conditions, adverse-reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Comparator AE rates are not an adequate basis for comparison of safety between products.
- Incidence of severe hypoglycemia was ≤1.5% across all placebo-controlled trials.1
- Incidence of severe hypoglycemia or blood glucose-confirmed hypoglycemia (% of patients) was 4% with Ozempic® 0.5 mg, 6% with Ozempic® 1 mg, and 11% with Lantus®.5,a
aDefined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions or blood glucose-confirmed symptomatic hypoglycemia (plasma glucose ≤3.1 mmol/L [56 mg/dL]).5
Adverse events ≥5% in SUSTAIN FORTE
AEs occurring in ≥5% of patients receiving Ozempic® 1 mg and 2 mg in SUSTAIN FORTE4
- In placebo-controlled trials, the most common adverse reactions reported in ≥5% of patients treated with Ozempic® are nausea, vomiting, diarrhea, abdominal pain, and constipation.1
- No new safety signals were identified. Gastrointestinal adverse reactions occurred more frequently among patients receiving Ozempic® 2 mg (34.0%) vs Ozempic® 1 mg (30.8%).4
- Incidence of severe hypoglycemia (level 3) was less than 1% for Ozempic® 1 mg and Ozempic® 2 mg in the SUSTAIN FORTE trial.4
SUSTAIN 5:
add-on to basal insulin
In patients with type 2
diabetes on basal insulin ± metformin
Secondary endpoint: mean change in body
weight from baseline at Week 301,6
Mean baseline: 202 lb
SUSTAIN FORTE:
Ozempic® 1 mg vs 2 mg
In patients with type 2
diabetes on metformin ± sulfonylurea
Secondary endpoint: mean
change in body weight from
baseline at Week 401,4
Mean baseline: 219 lb
Results based on sensitivity analyses of retrieved dropout population. SUSTAIN 5 and SUSTAIN FORTE were only powered to detect differences in weight from baseline to Week 30 and Week 40, respectively.
The estimated treatment difference was from baseline to Week 30 for SUSTAIN 5 and from baseline to Week 40 for SUSTAIN FORTE.
SUSTAIN 5: Results are from 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.6
SUSTAIN FORTE: Results are from 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.1,4
CI=confidence interval; ETD=estimated treatment difference; MET=metformin; NS=not significant.
Adverse events ≥5% in SUSTAIN 5
AEs occurring in ≥5% of participants treated with Ozempic® in SUSTAIN 56,7
AE=adverse event; GI=gastrointestinal.
- Incidence of severe hypoglycemia was ≤1.5% across all placebo-controlled trials.1
- Incidence of severe hypoglycemia or blood glucose-confirmed hypoglycemia (% of patients) was6,7:
- 8.3% with Ozempic® 0.5 mg + basal insulin ± MET
- 10.7% with Ozempic® 1 mg + basal insulin ± MET
- 5.3% with placebo + basal insulin ± MET
- Patients receiving Ozempic® in combination with an insulin secretagogue (eg, sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia.1
Adverse events ≥5% in SUSTAIN FORTE
AEs occurring in ≥5% of patients receiving Ozempic® 1 mg and 2 mg in SUSTAIN FORTE4
- In placebo-controlled trials, the most common adverse reactions reported in ≥5% of patients treated with Ozempic® are nausea, vomiting, diarrhea, abdominal pain, and constipation.1
- No new safety signals were identified. Gastrointestinal adverse reactions occurred more frequently among patients receiving Ozempic® 2 mg (34.0%) vs Ozempic® 1 mg (30.8%).4
- Incidence of severe hypoglycemia (level 3) was less than 1% for Ozempic® 1 mg and Ozempic® 2 mg in the SUSTAIN FORTE trial.4
More ways to help your patients with T2D
CV=cardiovascular; MACE=major adverse cardiovascular event; T2D=type 2 diabetes.
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 evaluate 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)5
Study design: 30-week, randomized, open-label, active-controlled, parallel-group, multinational, multicenter trial to evaluate 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 placebo1,6
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 mg4
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 mg (n=480) or 1 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% 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 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 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 and established CV disease.
Limitations of Use
- 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
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
- 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
- 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.
- 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. doi:10.1016/S2213-8587(18)30024-X
- 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 (supplemental appendix). Lancet Diabetes Endocrinol. 2018;6(4):275-286. doi:10.1016/S2213-8587(18)30024-X
- 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
- 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, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol. 2017:5(5):355-366. doi:10.1016/S2213-8587(17)30085-2
- Rodbard HW, Lingvay I, Reed J, et al. Semaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): a randomized, controlled trial. J Clin Endocrinol Metab. 2018;103(6):2291-2301. doi:10.1210/jc.2018-00070
- Data on file. Novo Nordisk Inc.; Plainsboro, NJ.