Yes, Zilretta is a steroid. Specifically, it contains triamcinolone acetonide, a synthetic corticosteroid that reduces inflammation. This is the same class of medication used in standard cortisone shots, not the muscle-building anabolic steroids associated with athletics. What makes Zilretta different from a typical steroid injection is how the drug is packaged and released inside your joint.
What Type of Steroid Zilretta Contains
Zilretta’s active ingredient, triamcinolone acetonide, is a glucocorticoid, a type of corticosteroid that mimics cortisol, the hormone your body naturally produces to control inflammation. When injected into a joint, it suppresses the inflammatory processes that cause pain and swelling in osteoarthritis. This is the same drug used in conventional knee injections for decades.
The distinction matters because “steroid” is a broad term. Corticosteroids like the one in Zilretta work by calming the immune response. Anabolic steroids, the kind banned in sports, promote muscle growth and affect sex hormones. They are completely different drugs with different effects, and Zilretta has nothing in common with them.
How Zilretta Differs From a Standard Steroid Shot
A conventional steroid injection floods the joint with medication all at once. Your body absorbs it quickly, which means the drug also leaks into your bloodstream relatively fast. Zilretta takes a different approach: the triamcinolone acetonide is embedded in tiny biodegradable microspheres, each roughly 45 micrometers across. These microspheres are too large to slip through the small gaps between cells lining the joint (which measure only 0.1 to 5 micrometers), so the medication stays trapped inside the knee rather than escaping into your circulation.
The drug releases in three phases. First, a small burst of medication comes off the surface of the microspheres shortly after injection. Then water gradually seeps into the polymer, creating tiny channels that allow the drug to diffuse out slowly over weeks. Finally, the microsphere material itself breaks apart, releasing whatever medication remains. The entire process delivers 32 mg of triamcinolone acetonide over roughly 12 weeks, compared to a standard injection where most of the drug is absorbed within days.
What Zilretta Is Approved to Treat
The FDA approved Zilretta specifically for osteoarthritis pain of the knee, delivered as a single intra-articular injection. It is not approved for the hip or shoulder, and the FDA label notes that its safety and effectiveness in those joints have not been evaluated. It is also not suitable for small joints like those in the hand.
Each dose is a single 5 mL injection containing 32 mg of triamcinolone acetonide. The FDA labeling states that the safety and efficacy of repeat injections have not been demonstrated. Animal studies on repeat dosing showed increased inflammation, tissue changes, and decreased cartilage proteoglycan content compared to the same dose of immediate-release triamcinolone, which raises questions about whether multiple rounds of Zilretta could affect joint health over time.
Blood Sugar Effects for People With Diabetes
One of the biggest concerns with any corticosteroid injection is blood sugar spikes, particularly for people with type 2 diabetes. Because Zilretta releases the drug slowly instead of all at once, it causes a noticeably smaller glucose disruption than a standard steroid shot.
In a study comparing Zilretta to an immediate-release triamcinolone injection in patients with knee osteoarthritis and type 2 diabetes, the differences were substantial. In the first three days after injection, the median maximum blood sugar increase was 92 mg/dL with Zilretta versus 169 mg/dL with the standard injection. Only 50% of Zilretta patients saw their glucose exceed 250 mg/dL, compared to 93% of patients who received the conventional shot. The standard injection also hit that 250 mg/dL threshold much faster, in a median of 6 hours versus 44 hours for Zilretta.
This doesn’t mean Zilretta is free of blood sugar effects. Half of the diabetic patients in the study still experienced significant glucose elevations. But the slower drug release clearly blunts the intensity and speed of the spike, which can make it easier to manage.
What to Expect From the Injection
Zilretta is injected directly into the knee joint, just like a standard cortisone shot. The procedure itself feels similar. Because the medication releases gradually, you may not feel the same rapid relief that comes from a conventional injection, where a large dose hits inflamed tissue all at once. Instead, the pain relief builds and is designed to last longer, with the microspheres delivering medication over approximately 12 weeks.
The side effects are generally consistent with what you’d expect from any corticosteroid joint injection: joint pain or swelling at the injection site, headache, and the systemic effects that come with corticosteroids entering the bloodstream (though at lower levels than a standard shot). The slow-release design reduces but does not eliminate the drug’s presence in the rest of your body.