In this study, we investigated whether preemptive administration of DT or DS would offer distinct advantages in managing pain, swelling, and trismus during the postoperative period. While clinical differences between the two groups were observed, these did not reach statistical significance. Clinically, rescue analgesia was required less frequently on the side treated with DT, and less edema was initially observed. Conversely, DS proved significantly more effective than DT in reducing edema between postoperative days 2 and 7. These findings suggest that DT may be particularly beneficial during the first 48 h, when pain is most severe and edema is increasing, while DS could be more effective in the later recovery phase for resolving postoperative edema more rapidly. Based on these results, tailoring NSAID prescriptions to the specific needs of the recovery period—using analgesic-anti-inflammatories during the early postoperative phase—could be a promising strategy. We believe this study provides “novelty value” by offering clinicians a new perspective on postoperative NSAID prescription strategies.

The use of rescue analgesics has been identified as a potential factor that can obscure the true effects of study drugs within a research group [17]. In our study, rescue analgesics were used, and this provided valuable data regarding the efficacy and duration of action of the NSAIDs administered. Because NSAIDs are generally dosed twice daily, the use of rescue analgesics helps to determine whether the prescribed regimen is sufficient to manage pain effectively at the given dosage. Increasing the dosage of analgesics raises the risk of side effects and toxicity; therefore, it is critical to establish the minimum effective dose and an appropriate dosing regimen tailored to the clinical scenario. The need for rescue analgesics in the DS group raises the question of whether a higher dosage or alternative analgesics should be considered for managing acute pain more effectively.

The patients in our study began their medications 1 h before the procedure, with 31.4% of the DT group and 41.2% of the DS group requiring paracetamol as a rescue analgesic. Although this approximately 10% lower usage in the DT group did not reach statistical significance, it may indicate a clinical advantage. Notably, although paracetamol is generally considered to have minimal anti-inflammatory effects, a previous study reported a contradictory finding [18]. This raises the possibility that the use of paracetamol as a rescue analgesic may have contributed to the faster reduction of edema observed in the DS group than in the DT group between days 2 and 7.

The time to reach the maximum plasma concentration for DT is 25–45 min, while that for DS is approximately 2 h [8, 19]. Although no statistically significant difference was found in the peak edema levels, clinically, less edema was observed on postoperative day 2 in the DT group than in the DS group. This clinical difference may be attributed to DT’s rapid attainment of the maximum plasma concentration, potentially making it more effective in suppressing early-stage inflammation during the period of surgical trauma. By day 7, the edema levels were similar in both groups, with the DS group showing greater success in reducing edema between days 2 and 7. This could be associated with the hydrophilic nature of the sodium salt compared with the trometamol salt, which may enhance its effectiveness in resolving edema. Future studies could explore whether administering DS 2 h before the procedure might produce different clinical and statistical outcomes regarding its effect on edema. However, because of diclofenac’s short plasma elimination half-life, preemptive administration 2 h prior is unlikely to extend the pain-free period provided by local anesthesia [15, 18, 20,21,22]. Additionally, initiating diclofenac preemptively 1 day before surgery has been reported to have no effect on trismus [23]. In our study, no statistically significant difference was observed between the groups in terms of trismus outcomes.

Converting drugs into water-soluble salt forms enhances their dissolution, absorption, and bioavailability after oral administration [24]. As a result, the clinical duration of action, absorption rate, dosage, and maximum effect value of ketoprofen and diclofenac differ from those of their salt forms, DT and DS. Studies comparing ketoprofen and diclofenac with their salt derivatives show that higher doses of the main active ingredients are often used, and the salt forms typically have a shorter onset of action. For instance, studies comparing the parent compounds typically administer ketoprofen and diclofenac at higher dosages than their salt forms [25, 26]. In one study, a single 100-mg dose of ketoprofen was compared with 75 mg of DS following impacted tooth extraction, and although pain scores favored ketoprofen, the difference was not statistically significant. However, the time to first analgesic intake was noted to be longer with ketoprofen [25]. Similarly, another study by Bahrgava et al. compared single doses of a 20 mg/70 cm2 ketoprofen patch with a 200 mg/50 cm2 diclofenac patch after impacted premolar tooth extraction, with ibuprofen as a rescue analgesic. Although ketoprofen demonstrated analgesic superiority, no statistically significant difference was found [26].

Anıl et al. administered a single dose of 50 mg DT and 75 mg DS parenterally during laparoscopic cholecystectomy [27]. In patients who received DT, both controlled morphine use and rescue analgesic requirements were lower than in the DS group, and the time to first analgesic use after surgery was longer [27]. Additionally, in the management of acute musculoskeletal injuries, orally administered DT has been shown to provide faster pain control than DS [28]. Our findings align with the literature; however, we did not identify any studies comparing the analgesic and anti-inflammatory effects of these two drugs on both soft and bone tissues.

One limitation of our study is the lack of homogeneity in the female-to-male ratio. This imbalance is largely due to a general trend observed in the literature, where women are more likely to undergo tooth extractions [29]. Male patients, even when extraction is indicated, tend to be less likely to proceed with the procedure. Additionally, the patient groups were formed during the active phase of the COVID-19 pandemic, a time when patients were still hesitant to seek dental treatment in hospitals, further contributing to this imbalance.

Another limitation is the absence of a placebo group in the study. However, the superiority of the NSAIDs used in this study over placebo has been repeatedly demonstrated in prior research. Furthermore, the use of experimental groups created within the same individual eliminates individual variability in drug response, enhancing the reliability and significance of the results.

The doses used in this study were selected based on typical daily requirements encountered in clinical practice and determined with consideration of the therapeutic efficacy of both drugs. While the dose ranges provided in product labeling allow for a broad therapeutic window, the risk of adverse effects increases with higher doses. For instance, DT doses of ≥ 50 mg are associated with a higher incidence of local bleeding [11, 14]. Furthermore, because pharmaceutical products on the market containing 25 mg of DT actually include 36.9 mg of DT, the threshold for potential side effects may be reached more quickly. This highlights that the optimal dose for each drug may not be universally applicable across all clinical scenarios. Therefore, pharmaceutical research should prioritize evaluating whether the desired clinical effects can be achieved with the minimum effective dose in the shortest possible time frame.

For pain, edema, and trismus following the extraction of impacted teeth, even minimal relief—such as a decrease of 1 point on the VAS or a slight improvement in mouth opening—can translate into significant comfort for patients. In split-mouth studies, the results hold particular clinical value because patients can directly compare the effects on the right and left sides. Therefore, even minor clinical differences are meaningful in terms of patient comfort and benefit, and a statistically significant difference may not always reflect clinically relevant improvements [30]. What truly matters is the impact on patients’ quality of life and its implications for clinical practice [31].