FDA adds a cardiovascular indication to Ozempic

The U.S. Food and Drug Administration approved a new indication for Ozempic (semaglutide) injection on January 16, 2020, allowing the drug to be marketed to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease ^[1][3]. The agency defines those events in the label as cardiovascular death, non-fatal myocardial infarction (heart attack) or non-fatal stroke ^[1].

The approval came through a prior approval supplemental new drug application, NDA 209637/S-003, that Novo Nordisk submitted on March 20, 2019 ^[1]. The FDA's approval letter was signed at 3:46 p.m. on January 16, 2020 by Lisa B. Yanoff, M.D., acting director of the Division of Metabolism and Endocrinology Products, and the approval took effect the same day ^[1].

What the approval was based on

The supplement added the new indication and revised the labeling to reflect results from the SUSTAIN 6 cardiovascular outcomes trial, described in the FDA letter as "A Long-term, Randomized, Double-blind, Placebo-controlled, Multinational, Multi-center Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes" ^[1]. The trial is registered on ClinicalTrials.gov as NCT01720446 ^[2].

The documents released with the approval do not spell out the size of the benefit seen in SUSTAIN 6 — the specific event rates and risk reductions are contained in the revised prescribing information rather than in the approval letter itself ^[1]. Anyone looking for those numbers will need to read the updated label once it is posted publicly.

The FDA also waived the pediatric study requirement for this application under the Pediatric Research Equity Act, stating that the necessary studies are "impossible or highly impracticable" ^[1]. In other words, this cardiovascular indication applies to adults only.

Ozempic was first approved in the United States on December 5, 2017 as an addition to diet and exercise to improve blood sugar control in adults with type 2 diabetes ^[3]. The cardiovascular indication is a second, separate reason a clinician can prescribe it. Semaglutide is a GLP-1 analog that stimulates insulin secretion and lowers glucagon secretion when blood glucose is high ^[3].

Why it matters for patients

An FDA indication is not just marketing language. It sets what a manufacturer can legally claim in advertising and promotional materials, which the company must submit to the agency's Office of Prescription Drug Promotion at the time of first use ^[1]. It also shapes how treatment guidelines and insurance coverage rules describe a drug's role, because the label is the document payers and prescribers point to.

Practically, this means adults with type 2 diabetes who have already had heart problems now have an FDA-recognized cardiovascular reason on the Ozempic label, not only a blood sugar reason. The indication is limited to that group: people with type 2 diabetes and established cardiovascular disease ^[1]. It does not extend to people without diabetes, and it does not cover weight loss.

The new indication does not change the drug's safety profile. Ozempic carries a boxed warning for thyroid C-cell tumors, and its warnings and precautions include acute pancreatitis, diabetic retinopathy complications, hypoglycemia, acute kidney injury from volume depletion, serious hypersensitivity reactions and acute gallbladder disease ^[3]. The most common side effects reported in at least 5% of people taking the injection are nausea, vomiting, diarrhea, abdominal pain and constipation ^[3]. Ozempic is given as a once-weekly injection under the skin, at any time of day, with or without meals ^[3].

What happens next

Under the terms of the approval letter, Novo Nordisk had to submit the final content of labeling — the prescribing information, medication guide and instructions for use — in structured product labeling format within 14 days of January 16, 2020, meaning by the end of that month ^[1]. That filing is what makes the revised label visible in public labeling repositories, so patients and clinicians can read the SUSTAIN 6 data section themselves ^[1].

The enclosures listed with the approval include instructions for use for the 0.25 or 0.5 mg and 1 mg pens in 1.5 mL, approved November 27, 2019, and for the 1 mg, 3 mL pen approved April 9, 2019 ^[1]. Whether the cardiovascular indication changes pricing or insurance coverage is not addressed in these documents.