SUSTAIN-6 reported fewer cardiovascular events with semaglutide and more retinopathy

The SUSTAIN-6 cardiovascular outcomes trial reported that semaglutide lowered the rate of major adverse cardiovascular events in adults with type 2 diabetes at high cardiovascular risk. Diabetic-retinopathy complications, meanwhile, were more common with semaglutide than with placebo in that same population ^[2].

Semaglutide is the molecule sold as Ozempic, Rybelsus and Wegovy, each prescription-only in the United States ^[1]. It is given either as a subcutaneous injection or as an oral tablet, and its elimination half-life is about seven days ^[1].

SUSTAIN-6 enrolled adults with type 2 diabetes and elevated heart risk ^[2]. Figures that usually accompany a trial report — the hazard ratio for the heart endpoint, the absolute event rates in each arm, how many people took part, and which specific events made up the composite measure — have not been reported. Whether eye outcomes were a planned endpoint of the study or came out of safety monitoring has not been reported either.

The eye result is generally read alongside the speed of glucose improvement. Diabetic retinopathy can worsen temporarily when blood sugar falls quickly in someone who already has retinal disease, a pattern known well before GLP-1 medicines existed ^[2]. A 2026 systematic review described retinal findings across GLP-1 studies as inconsistent: apart from the SUSTAIN-6 signal, randomized trials generally did not show more retinopathy progression, and results from observational databases varied ^[2].

Why it matters for patients

Two findings from one high-risk group point in different directions. For an adult with type 2 diabetes and existing heart risk, a lower rate of major cardiovascular events is the kind of outcome regulators weigh when deciding what a diabetes drug's label should say ^[2]. For someone who already has diabetic retinopathy, the eye signal means the condition of the retina at the start of treatment and the pace of glucose change both matter, not the drug on its own ^[2].

NAION and diabetic retinopathy are separate conditions — one affects the optic nerve, the other the small blood vessels of the retina — and regulators outside the United States have revised safety information as evidence developed. Because wording differs by product and by country, the current FDA label and a clinician's guidance are the reference points in the US ^[2].

Sudden vision loss, a dark curtain, a new missing area of the visual field, or rapidly worsening eyesight call for urgent medical evaluation rather than a routine appointment, according to regulators and clinical guidance ^[2]. Guideline-based retinal screening still applies to people with diabetes no matter which medicine they take, and there is no evidence-based rule that everyone starting a GLP-1 drug needs a special eye examination solely because of the prescription ^[2].

What happens next

In 2025 the European Medicines Agency concluded that NAION should be listed as a very rare adverse effect of semaglutide medicines. Its review estimated about one additional case per 10,000 person-years of treatment and described epidemiologic estimates near a two-fold relative increase among adults with type 2 diabetes ^[2]. Australia's Therapeutic Goods Administration followed in July 2026 with class-wide warning updates for marketed GLP-1 receptor agonists, advising prompt medical attention for sudden vision loss ^[2]. A 2026 North American neuro-ophthalmology consensus statement called for counseling tied to the specific diagnosis rather than blanket conclusions about the entire drug class ^[2].

Whether US labeling for semaglutide has changed in response has not been reported.