Consider why once-weekly Ozempic® should be the first injectable for most patients
PEER INSIGHTS
Is it time to reconsider your options?
You have options when it comes to prescribing the first injectable for your adult patients with type 2 diabetes. Hear from 2 health care professionals on why they choose a GLP-1 RA therapy as the first injectable for some of their patients.
CRAIG WIERUM | MD, FACE
Endocrinologist
Heritage Medical Associates
Nashville, TN
LISA COCO | NP
Board Certified Registered Nurse Practitioner, Certified Diabetes Care and Education Specialist
Jefferson University Physicians
Philadelphia, PA
When additional glycemic control is needed, many health care professionals prescribe a basal insulin as their adult patients’ first injectable after metformin. While there are patients who benefit from the use of a basal insulin, there are other options that may help patients reach their A1C goals.
The ADA guidelines recommend GLP-1 RA therapies prior to basal insulin for most adult patients with type 2 diabetes who need the greater efficacy of an injectable medication. This recommendation is based on efficacy, side effects, cost, and patient preferences.1
“In my experience, my peers are more familiar with basal insulin and understand the benefits and side effects. There would be a huge impact if they knew about the once-weekly dosing options available with GLP-1 RA therapies.2
When I talk with my patients, I take my time explaining the guidelines and treatment, as well as what causes hypoglycemic events. I stress that every treatment plan is different for each patient and patients like that GLP-1 RA therapy offers once-weekly dosing.”
Lisa Coco NP
“The ADA guidelines recommend GLP-1 RA therapies for most patients with type 2 diabetes who need the greater glucose-lowering effect of an injectable medication.1 I take into consideration the once-weekly dosing options, efficacy, cost, and tolerability issues when prescribing a treatment.”1
Craig Wierum MD, FACE
MECHANISM OF ACTION
The different ways GLP-1 RA therapy and basal insulin work after entering the bloodstream
GLP-1 RA therapy:
Signals the pancreas
- To release the body’s own insulin, if blood sugar is high3,4
- To lower glucagon secretion, which signals the liver to stop releasing glucose into the blood3,4
Works in the gut by slowing gastric emptying3
Basal insulin:
Signals muscle and fat cells to absorb sugar and turn it into energy5
Signals the liver to store sugar instead of releasing it into the blood5
SUSTAIN 4
See how once-weekly Ozempic® compared to Lantus® in a head-to-head trial3,6
When patients are no longer reaching their A1C goals with oral medications and you are thinking about their first injectable, it’s important to consider the efficacy of the treatments you prescribe. The SUSTAIN 4 clinical trial was designed to compare the efficacy and safety of Ozempic® versus study-titrated Lantus® in adult patients with type 2 diabetes.2,6
PATIENTS:
1089
KEY INCLUSION CRITERIA:
Insulin-naïve, T2D, inadequately controlled on metformin alone or in combination with sulfonylurea
STUDY DESIGN:
30-week, randomized, open-label, active-controlled, parallel-group, multinational, multicenter trial. 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 at their discretion between study visits.
PRIMARY ENDPOINT
Based on study protocol insulin titration, in insulin-naïve patients on metformin with or without sulfonylurea
Ozempic® demonstrated statistically significant A1C reductions vs Lantus®2,6
Primary endpoint: Mean change in A1C from baseline at Week 30
26% of insulin patients titrated to goal by Week 30. Mean daily insulin dose: 29 U/day.2
Results are from a 30-week, randomized, open-label, active-controlled trial in 1089 adult patients with type 2 diabetes comparing Ozempic® 0.5 mg and Ozempic® 1 mg to Lantus®.2,6
“My peers and I were quite surprised by the A1C results in SUSTAIN 4. There were greater A1C reductions with Ozempic® vs study-titrated Lantus®.”2
CRAIG WIERUM | MD, FACE
SECONDARY ENDPOINT
Based on study protocol insulin titration, in insulin-naïve patients on metformin with or without sulfonylurea
Ozempic® demonstrated statistically significant reduction in body weight vs Lantus®2,6
Ozempic® is not indicated for weight loss.
Secondary endpoint: Mean change in body weight from baseline at Week 30
Results are from a 30-week, randomized, open-label, active-controlled trial in 1089 adult patients with type 2 diabetes comparing Ozempic® 0.5 mg and Ozempic® 1 mg to Lantus®.2,6
CI=confidence interval; ETD=estimated treatment difference.
“Even though Ozempic® is not indicated for weight loss, I was impressed by the approximate 12-lb mean weight difference with Ozempic® 1 mg vs study-titrated Lantus®.”2
Lisa Coco | NP
ADVERSE EVENTS
Adverse events (AEs) occurring in ≥5% of participants in SUSTAIN 46
SUSTAIN 4 was not designed to evaluate relative safety between Ozempic® and Lantus®
- In placebo-controlled trials, the most common adverse reactions reported in ≥5% of patients treated with Ozempic® are nausea, vomiting, diarrhea, abdominal pain, and constipation2
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice2
- Comparator adverse event rates are not an adequate basis for comparison of safety between products
- Incidence of severe hypoglycemia was ≤1.5% across all placebo-controlled trials2
- 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®6,a
AE=adverse events; GI=gastrointestinal.
aDefined as an event requiring assistance of another person to actively administer carbohydrates or glucagon, or take other corrective actions or blood glucose-confirmed symptomatic hypoglycemia (plasma glucose ≤3.1 mmol/L [56 mg/dL]).6
Results from a 30-week, randomized, open-label, active-controlled trial in 1089 adult, insulin-naïve patients with type 2 diabetes.2,6
STUDY DESIGN
SUSTAIN 4: Head-to-head vs Lantus® (insulin glargine U-100)2,6
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 endpoint: Mean change in body weight from baseline at Week 30.
Ozempic®—A1C control within your control for a range of patient needs
See results for SUSTAIN 4 and SUSTAIN FORTE, a 40-week trial comparing Ozempic® 1 mg and Ozempic® 2 mg.
See the insulin response of T2D patients taking Ozempic® vs healthy people
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 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:
- American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes—2021. Diabetes Care. 2021;44(Suppl.1):S111-S124.
- Ozempic® [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; March 2022.
- Drucker DJ. The biology of incretin hormones. Cell Metab. 2006;3:153-165.
- Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013;17(6):819-837.
- Dimitriadis G, Mitrou P, Lambadiari V, Maratou E, Raptis S. Insulin effects in muscle and adipose tissue. Diabetes Res Clin Pract. 2011;93S:S52-S59.
- 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.