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Objective: To improve clinical and radiographic results in patients with periodontitis, this systematic review assessed the efficacy of metformin (MF) as an adjuvant to surgical and nonsurgical periodontal therapy. Methods: Patients with periodontitis (P), MF as an adjuvant (I), periodontal therapy alone, or placebo (C), and outcomes such as bone regeneration (O), clinical attachment level (CAL), and probing depth (PD), were evaluated with the PICO framework. Between June 15 and July 1, 2025, we searched for in vitro, in vivo, and randomized controlled trials (RCTs) published between June 2015 and June 2025 in PubMed, Google Scholar, ScienceDirect, and Semantic Scholar. Data were narratively synthesized according to MF concentration (0.5-1.5%), outcome measures, and patient type. The Cochrane tools SYRCLE and QUIN were used to assess risk of bias for RCTs, animal studies, and in vitro studies. Results: The analysis included 15 RCTs, 10 in vitro studies, and 8 in vivo studies among 4005 identified records. The most commonly used formulation was local MF gel. Follow-up times ranged from 1 to 9 months. MF, in contrast to scaling and root planing or placebo, produced vertical bone fill as high as 26.8%, a CAL gain of 1.5-2.7 mm, and a PD decrease of 1.5-3.4 mm. Experimental investigations had moderate risk of bias, whereas RCTs had low risk of bias. Conclusion: MF's osteogenic and anti-inflammatory qualities make it a promising adjuvant in periodontal therapy. However, the need for additional long-term research was highlighted by the study heterogeneity, limited follow-up periods, and a lack of meta-analysis.
Uddin et al. (Wed,) studied this question.