Healing Response to Hyaluronic Acid Supplemented with Selected Amino Acids: A Pooled Analysis of Two Clinical Studies

Background/Objectives: Diabetes is associated with impaired wound healing, with consequences for tissue recovery across surgical procedures. In the oral context, hyaluronic acid-based adjunctive therapies have shown promise in improving early post-extraction healing in diabetes; however, clinical evidence remains limited. Different supplemented HA-based formulations yield heterogenous healing outcomes. Moreover, whether age or diabetes duration influences the effect of these adjunctive therapies remains to be established. Methods: We conducted an individual-participant-data pooled analysis of two randomized controlled trials that evaluated the use of hyaluronic acid supplemented with two different sets of selected amino acids; individual data from each trial was combined into a single dataset. Results: In this pooled analysis, modified healing index scores improved significantly over time. When each intervention was evaluated relative to its corresponding control, hyaluronic acid plus six pro-collagen synthesis amino acids produced a significantly greater improvement in healing response over time than the other HA-based formulation, after adjustment for age (Greenhouse–Geisser: time × treatment: F = 5.821, p < 0.001) and diabetes duration (Greenhouse–Geisser: time × treatment: F = 4.939, p < 0.001). Neither age nor diabetes duration significantly modified the healing trajectory (Greenhouse–Geisser: time × age: F = 2.536, p = 0.083; time × diabetes duration: F = 0.131, p = 0.878). No clear association with age or diabetes duration was observed. Conclusions: Supplementing hyaluronic acid with six selected amino acids associated with a significantly faster post-extraction tissue recovery in patients with diabetes. Moreover, treatment choice was relevant regardless of age or years since diabetes diagnosis.