Restylane Refyne and Defyne: One Approval, One Word of Difference, and a Split-Face Trial
Reviewed for medical accuracy against our Medical Review Board · Last updated 2 September 2026
Part of Dermal Fillers
Restylane Refyne and Restylane Defyne were approved on the same day, in the same FDA application, for the same area, described in one trial document covering both. We cover them on one page for that reason.
Their trials contain something we have not seen reported anywhere: each patient received the Restylane product on one side of their face and a competitor's filler on the other side. And on those same faces, the competitor's side scored slightly better at every timepoint.
What that does and does not mean. Both studies were non-inferiority studies with a pre-set margin, and both passed. The correct reading is "not meaningfully worse on the same face". It is not evidence that Refyne or Defyne is better than what it was tested against, and the published numbers do not show them outperforming it.
Two products, one approval, one word of difference
Both came through P140029, the original application, approved 9 December 2016. Here is the approved wording, side by side.
| Product | Approved for |
|---|---|
| Restylane Refyne | Injection into the mid to deep dermis for correction of moderate to severe facial wrinkles and folds, such as nasolabial folds, in patients over 21 |
| Restylane Defyne | Injection into the mid to deep dermis for correction of moderate to severe deep facial wrinkles and folds, in patients over 21 |
The word "deep" is the entire difference in the indication. Defyne is the firmer gel, positioned for deeper folds; Refyne is the softer one, positioned for more moderate lines where flexibility matters more. Nasolabial folds, the lines running from the nose to the corners of the mouth, are the area both were tested on.
They have never been compared with each other in a trial. Each was tested against a competitor's filler, in two separate studies, so anyone telling you one is stronger than the other is describing gel firmness rather than published evidence.
The split-face design
The FDA document describes both studies in the same phrase: "randomized, evaluator-blinded, active-controlled, multi-center, split-face clinical studies".
Split-face means exactly what it sounds like. One nasolabial fold got the Restylane product. The other got the control, which the document specifies as an FDA-approved hyaluronic acid filler with similar characteristics to whichever Restylane product it was matched against, and without lidocaine. A blinded evaluator then scored each side.
This is a strong design, for the same reason the Restylane Lyft hand study was: the patient is their own control. Two people age, heal and photograph differently, so comparing groups of people always measures some of the people. Comparing the two halves of one face removes that entirely. The statistics reflect it: the analysis was built on the mean paired difference between the two sides.
Subjects had one touch-up at three weeks if needed, then follow-up at 1 and 3 weeks and at 12, 24, 36 and 48 weeks. They also kept a safety diary for three weeks after each treatment, recording bruising, swelling, redness, lump or bump formation, pain, tenderness and itching.
What the numbers actually were
The primary measure was change from baseline on the Wrinkle Severity Rating Scale, a 5-point scale, at 24 weeks after the final initial injection, each side judged by a blinded evaluator. A responder improved by at least one grade.
| Timepoint | Restylane Refyne | Control side | Restylane Defyne | Control side |
|---|---|---|---|---|
| Week 24 | 78.8% | 83.5% | 77.8% | 85.2% |
| Week 36 | 78.0% | 80.5% | - | - |
| Week 48 | 66.7% | 72.8% | - | - |
On the underlying scale the gap was small. At Week 24 the mean change was -1.3 for Refyne against -1.4 for its control, a tenth of a point on a 5-point scale.
Two things are worth taking from this table rather than one. First, both products worked: roughly four in five patients improved by at least a grade at 24 weeks, and two thirds were still responders at 48 weeks. Second, the side treated with the comparison filler did marginally better, on the same faces, at every point measured.
What a non-inferiority pass tells you
Read this before drawing a conclusion from the table above, because both halves of the finding mislead on their own.
These were non-inferiority studies. The pre-specified margin was 0.4 WSRS units on the paired difference between the two sides, and non-inferiority was declared if the confidence interval stayed within it. Both studies passed. That is a legitimate basis for FDA approval and is used throughout medicine, particularly where a new product is not expected to beat an existing one but to match it while differing in some other way, such as how the gel behaves in mobile areas of the face.
So the accurate statement is: Refyne and Defyne were shown not to be meaningfully worse than an established filler, measured on the same faces. What the published evidence does not show is either product outperforming what it was tested against.
The other consequence is the one we make across this cluster: because these trials had no untreated arm, they never produced a figure for how many people would have been scored as improved with no treatment at all. On our Lyft page, untreated groups scored 16.7% and 21.2% depending on the scale, and on jawline filler one untreated group scored 39.1%. Without such a number here, a 78.8% cannot be compared with a percentage from any trial that had one.
Defyne also has a chin approval
Defyne picked up a second indication on 29 January 2021, through P140029/S027: augmentation of the chin region to improve chin profile in patients with mild to moderate chin retrusion over 21.
Refyne has no chin approval. So within this pair, only Defyne is approved for the chin, and only for mild to moderate retrusion. It is one of three products approved for the chin in total, and we compare all three, including their different measurement scales, on chin filler.
Neither product is approved for the marionette lines that run from the mouth corners to the jaw, though the region sits next to the folds they were tested on. For what does address that area, see marionette lines.
Who was actually studied
| Refyne study | Defyne study | |
|---|---|---|
| Patients treated | 170 | 162 |
| Sites | 12 | 11 |
| Female | 94.1% (160/170) | 96.3% (156/162) |
| Male | 5.9% (10/170) | 3.7% (6/162) |
| Mean age | 53.9 | 53.7 |
| Age range | 26 to 77 | 34 to 75 |
| Aged 65 and above | 6.5% (11) | 9.9% (16) |
Both were studies of women in their fifties with nasolabial folds. Sixteen men across both trials combined, and fewer than one patient in ten aged 65 or over. The data through date was 19 January 2012, so this evidence is now well over a decade old, which is normal for a filler approval and worth knowing.
On adverse events, the Refyne study reported device and injection-related events in 7.1% of patients (12 of 170). No patient discontinued the Refyne study because of an adverse event. Four discontinued the Defyne study for adverse events, and the document lists causes unrelated to the filler, including a lung cancer and a hip injury.
What to ask before you book
- Refyne or Defyne, and on what basis? The only difference in the approvals is the word "deep". No trial has compared them, so the answer should be about your folds and the gel's firmness, not about published evidence.
- Is my chin in scope? Only Defyne has a chin approval, and only for mild to moderate retrusion.
- Will I need a touch-up? The trials allowed one at three weeks and many patients had it. Ask whether that is included in the price.
- What does the first three weeks look like? Patients kept a diary for exactly that long, recording bruising, swelling, lumps and tenderness.
- What happens at a year? Two thirds of patients were still responders at 48 weeks, so a third were not.
- Can it be dissolved? Yes, both are hyaluronic acid, so hyaluronidase works.
For the whole range see our Restylane hub, for lips Restylane Kysse, and filler recovery for what the first two weeks involve. Filler complications covers what is not normal recovery. Dermal fillers covers the FDA record across every approved filler.
Frequently asked questions
What is the difference between Restylane Refyne and Defyne?
Which is stronger, Refyne or Defyne?
Do Refyne and Defyne work better than other fillers?
How long do Restylane Refyne and Defyne last?
What is a split-face study?
Is Restylane Defyne approved for the chin?
How old is the evidence for Refyne and Defyne?
Sources
Every figure on this page was read from the documents below rather than from a clinic or a manufacturer's marketing. They open in a new tab so you can check any claim here against its source.
- Summary of Safety and Effectiveness Data, P140029, Restylane Refyne and Restylane Defyne, US Food and Drug Administration
- Summary of Safety and Effectiveness Data, P140029/S027, Restylane Defyne chin, US Food and Drug Administration
- Dermal fillers (soft tissue fillers), US Food and Drug Administration
Know the count before the quote. The unit count is half the bill, and a low per-unit rate recovered by a high unit count is the commonest way a deal is not one. How to tell.
Deciding which area, not how many units? Botox by facial area covers what each zone actually achieves, which four are FDA approved, and the things Botox cannot fix at all.
