Systemic Metformin May Slow PCO, Study Says

A new study reports that systemically administered metformin reaches the human lens capsule at measurable concentrations. In in vitro experiments, these concentrations were associated with a statistically significant suppression of human lens epithelial cell proliferation, which leads to posterior capsule opacification. In their paper, researchers speculate on the potential of drug-eluting IOL materials in the future. Photo: Gleb Sukhovolskiy, OD. Click image to enlarge. The most common long-term complication of cataract surgery is posterior capsule opacification (PCO), experienced by approximately 20% to 30% of patients within five years following surgery. Understanding the pathophysiology of PCO, which involves the proliferation of lens epithelial cells (LECs) plus risk factors such as age and systemic disease, may help determine what could protect against this complication. Recent research has focused on type 2 diabetes, which has inconsistent evidence regarding its effect on PCO. In particular, some believe that the antidiabetic drug metformin may help modulate this process, and a new   study recently bolstered this hypothesis with results suggesting that the drug can reach the human lens capsule and reduce LEC proliferation in vitro. For their study, researchers in Vienna obtained lens capsule specimens from 20 patients (one eye per patient) undergoing routine cataract surgery. Eligible patients had a confirmed diagnosis of type 2 diabetes treated with oral metformin and age-related cataract. Patients were stratified into a low-dose group (≤1000mg/day) and a high-dose group (>1000mg/day). Researchers also obtained 20 anterior lens capsules from non-diabetic donors, 16 of which were eligible for the study. Metformin concentrations were measured in lens capsule tissue and serum.  According to their results, there were no significant lens capsule concentrations between groups; however, in serum, the inverse pattern was observed: the low-dose group exhibited higher concentrations (mean 890.2 pg/µL) compared with the high-dose group (mean 303.8 pg/µL), without statistical significance. Clinical characteristics differed between groups, the authors noted in their study. Patients in the high-dose cohort were significantly younger (mean 70.3 vs. 75.9 years) and had a longer duration of diabetes (21.1 vs. 11.2 years).  To further examine the biological effects of these intracapsular concentrations, the researchers performed an in vitro assay using the donor lens capsules. Explants were cultured for 14 days in either standard medium (control) or medium supplemented with metformin at 0.75 pg/µL, corresponding to the mean concentration detected in patient capsules in the previous experiments. There was a highly significant effect of time in both groups, and the interaction between time and treatment was also significant, indicating that metformin reduced proliferation compared with controls. Describing these results, the authors wrote, “Collectively, these findings demonstrate that metformin reaches the lens capsule at measurable concentrations linked to systemic levels, possibly influenced by age and metabolic activity.” They continued, “Our in vitro experiments provide functional evidence that even low intracapsular concentrations of metformin, comparable to those measured in patients, substantially suppress LEC proliferation.” Additional analysis, they noted, revealed a sustained anti-proliferative effect. “These results support the hypothesis that metformin interferes with pathways driving secondary cataract formation.” The clinical implications of this study may be noteworthy, as it suggests that systemic metformin could reduce the incidence of PCO after cataract surgery. In conjunction with the current cornerstone of PCO prevention—IOL design—incorporating metformin into IOL surfaces or slow-release reservoirs may be a future goal, although it remains hypothetical until rigorous trials are completed, the authors wrote. Study limitations include the modest sample size and the absence of direct intracellular metformin quantification in cultured LECs. “Importantly, metformin was detectable in human lens capsule tissue in vivo despite systemic metabolism and clearance, and corresponding concentrations were associated with a statistically significant attenuation of proliferation in vitro,” they wrote.  In conclusion, the researchers say this is the first evidence of systemically administered metformin reaching the human lens capsule, suppressing LEC proliferation. “These results support the hypothesis that metformin may serve as a pharmacological adjunct to current mechanical strategies for PCO prevention,” they wrote, calling for expanded patient cohorts in future research efforts.Click here for the journal source. Spartalis C, Ruiss M, Dechat T, et al. Intracapsular metformin bioactivity and its role in posterior capsule opacification. British Journal of Ophthalmology. February 26, 2026. [Epub ahead of print.]  This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.