Background: Dental caries remains a global problem that causes disproportionate suffering in underserved populations. Simple interventions are needed to improve patient experience, clinical and cost-effectiveness, and access to care. The self-assembling peptide P11-4 is a recently developed, non-invasive treatment that regenerates enamel in initial caries lesions. Studies reviewed: We conducted a systematic review and meta-analysis on the effectiveness of the P11-4 products CurodontTM Repair (CR) and CurodontTM Repair Fluoride Plus (CRFP) on initial caries lesions. Primary outcomes were lesion progression after 24 months, caries arrest, and cavitation. Secondary outcomes were changes in merged International Caries Detection and Assessment System (ICDAS) score, Quantitative Light Fluorescence, esthetic appearance, and lesion size. Results: Six clinical trials comparing CR to controls met the inclusion criteria. Results of this review represent two primary and two secondary outcomes. When compared to parallel groups, CR improved caries arrest (RR: 1.82; 95% CI: 1.32 to 2.50; 45% attributable risk; 95% CI: 24 to 60%) and decreased lesion size by 32% (Hedge g: -0.59; CI: -1.03 to -0.15). We observed positive trends for avoiding cavitation (RR: 0.32; CI: 0.10 to 1.06) and lowering merged ICDAS score (RR: 3.68; CI: 0.42 to 32.3). No studies used CRFP or reported adverse esthetic changes. Practical implications: CR has a treatment effect on caries arrest and decreased lesion size. Two trials contributing to the caries arrest result had non-masked assessors, and all trials had elevated risks of bias. We recommend conducting longer trials. CR is a promising treatment for initial caries lesions.

Authors not affiliated with CareQuest declare no financial conflict of interest. CareQuest Innovation Partners, a wholly owned subsidiary of CareQuest Institute for Oral Health, entered into a Collaboration Agreement that contains a financial arrangement with vVARDIS in 2021. Under the Collaboration Agreement, CareQuest Innovation Partners will receive a percentage of vVARDIS revenues from the sale of a new Curodont Repair Fluoride Plus product V3 designed for the US Medicaid market.

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=304794

There is no funding to report related to this work.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

All human data are from publicly published clinical trial papers.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.