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There is limited evidence on pharmacological interventions capable of slowing down disease progression in non-diabetic patients. Metformin, widely used to treat type 2 diabetes, has shown potential nephroprotective effects through activation of AMPK and inhibition of the mTOR pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Embase and Cochrane databases were searched for randomized clinical trials (RCTs) comparing metformin versus placebo or standard care in non-diabetic patients with ADPKD. Standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated via random-effects model. Heterogeneity was assessed using the I2 test. Statistical analyses were performed using Review Manager, version 5.4, and R Software, version 4.4.2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four RCTs were included, comprising 213 patients. Average follow-up ranged from 0.15 to 2\u2009years. No significant differences were observed in the decline of kidney function (SMD: 0.19; 95% CI, \u22120.08 to 0.46;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.17) or in height-adjusted total kidney volume (htTKV) progression (SMD: 0.09; 95% CI, \u22120.20 to 0.38;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.53). Gastrointestinal adverse events were more frequent in the metformin group (RR: 2.93; 95% CI, 1.51 to 5.67;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0014), while the incidence of hypoglycemia did not differ between groups (RR: 1.04; 95% CI, 0.36 to 3.00;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.948). The pooled prevalence of tolerability-related discontinuation or dose reduction due to adverse effects was 37.38% (95% CI: 12.15 to 72.04%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This meta-analysis suggests that metformin does not significantly affect the rate of kidney function decline in non-diabetic patients with ADPKD. Its impact on kidney volume remains uncertain, while gastrointestinal symptoms, although more common, were generally mild. However, interpretation is limited by the small number of trials, modest sample sizes, and relatively short follow-up durations, which reduce the ability to assess long-term outcomes. Larger and longer studies are needed to clarify the potential role of metformin in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p>PROSPERO CRD420251062402.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12882-025-04575-5","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T11:46:47Z","timestamp":1763466407000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin in non-diabetic patients with autosomal dominant polycystic kidney disease: a systematic review and meta-analysis of randomized controlled trials"],"prefix":"10.1186","volume":"26","author":[{"given":"Vitor","family":"Almeida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Maciel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Beatriz","family":"Valverde Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ferraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisalice","family":"Afonso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Dibo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Nunes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"issue":"10174","key":"4575_CR1","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/S0140-6736(18)32782-X","volume":"393","author":"E Cornec-Le Gall","year":"2019","unstructured":"Cornec-Le Gall E, Alam A, Perrone RD. 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