A summary of published research, not medical advice. See the Disclaimer.
All 1369 studies in the study browser
Included: human randomized controlled trials, systematic reviews and meta-analyses on metformin indexed in PubMed. A PubMed search on October 15, 2026 returned 2818 records. 1369 remain after excluding protocols, retractions, comments, papers that did not study metformin as the intervention or exposure and trials that measured no effect covered in the article. Below are the 150 highest-scored of 670 reviews and the 25 highest-scored individual studies. The study browser has the rest.
Scores run from 1 to 5 and rate study design only. The rules and reason codes are on Study Scores. Each finding restates the abstract's own conclusion.
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| Score | Study | Design, n | Finding |
|---|---|---|---|
| 5 (MA +large) | Kumar, 2026 | Meta-analysis, 5 studies, n=7,968 | Females had significantly higher odds of metformin-associated GIAEs than males (OR 1.85, 95% CI 1.58-2.17), with consistent findings in sensitivity analyses. Females may have a higher risk of metformin-associated GIAEs than... |
| 5 (MA +large) | Murtaza, 2026 | Meta-analysis, 2025 studies, n=187 | While glucocorticoids remain essential in various clinical contexts, their detrimental effects on glucose metabolism are well documented. This study supports metformin as a promising preventive treatment in non-diabetic patients... |
| 5 (MA +large) | Krysiak, 2026 | Meta-analysis, 51 studies | Our meta-analysis, the largest one conducted to date, indicates that metformin does not significantly affect circulating gonadotropin levels in reproductive-age women with PCOS. |
| 5 (MA +large) | Kim, 2026 | Meta-analysis, 41 studies | This largest systematic review demonstrates that diabetes mellitus is associated with worse RCC outcomes across all outcomes. Further research is warranted to confirm its significance on RCC prognosis. |
| 5 (MA +large) | Chen, 2026 | Meta-analysis, 10 studies, n=243,221 | Metformin use in patients with T2DM and OA is associated with significant reductions in pain and a decreased risk of TKR. Subgroup findings suggest that the benefits are dose- and duration-dependent, with RCT evidence strongly... |
| 5 (MA +large) | Rahmanian, 2026 | Meta-analysis, 31 studies, n=167,683 | Metformin use is reported to be associated with favorable prognostic outcomes in individuals with CRC, particularly among those with type 2 diabetes. However, its role in disease recurrence remains uncertain. |
| 5 (MA +large) | Theodoridis, 2026 | Meta-analysis, 19 studies | Metformin may have a role as an adjuvant therapy in managing overweight and obesity among the paediatric population. Regarding the concentrations of adipokines and hormones, the results are inconclusive. |
| 5 (MA +large) | Getu, 2026 | Meta-analysis, 18 studies, n=1,300,820 | Metformin does not significantly prolong the overall survival and progressivefree survival of cancer patients, but it may effectively reduce the risk of cancer occurrence. |
| 5 (MA +large) | Kamrul-Hasan, 2025 | Meta-analysis, 6 studies, n=317,905 | Such results must be considered cautiously, as the included studies are observational and have a moderate risk of bias. Randomised controlled trials with diverse global representation are essential for clarifying the relationship... |
| 5 (MA +large) | Ling, 2025 | Meta-analysis, 19 studies, n=1,657 | The combination of liraglutide and metformin resulted in greater improvements in body weight, blood sugar levels, insulin sensitivity, hormone balance (including LH, FSH and testosterone) and cholesterol profiles. These findings... |
| 5 (MA +large) | Rangraze, 2025 | Meta-analysis, 65 studies | Conclusions: Metformin intake seems to lower the chances of developing several types of cancers, especially breast and colorectal cancers, but the observational designs hinder determining the causal factors for observational... |
| 5 (MA +large) | Xu, 2025 | Meta-analysis, 23 studies, n=9,144 | As add-on therapy, SGLT2is demonstrated favourable antidiabetic efficacy and acceptable safety. 300 mg of canagliflozin was the best option among the included interventions considering favourable glucose control and WL. Some... |
| 5 (MA +large) | Fu, 2025 | Meta-analysis, 18 studies, n=7,975 | Metformin-exposed children did not differ in adiposity measures compared with their non-exposed peers in later childhood. This adds to the growing body of evidence supporting the long-term safety of metformin use in pregnancy. |
| 5 (MA +large) | Xie, 2025 | Meta-analysis, 16 studies | Our meta-analysis indicated that the use of metformin might reduce the EC incidence and improve the OS in EC patients with diabetes. |
| 5 (MA +large) | Zhang, 2025 | Meta-analysis, 11 studies, n=81,738 | SGLT-2i and GLP-1 RAs have the effects of cardiovascular benefits for T2DM patients regardless of baseline metformin use. |
| 5 (MA +large) | Peng, 2025 | Meta-analysis, 20 studies, n=1,070 | This updated meta-analysis investigated the durations and dosages of metformin use in patients with schizophrenia experiencing antipsychotic-induced weight gain. The findings highlight the need for additional large-scale research... |
| 5 (MA +large) | Huang, 2025 | Meta-analysis, 15 studies, n=20,595 | In individuals with T2DM and CHF, the use of Met is linked to a decreased likelihood of all-cause mortality and cardiovascular-related mortality. Furthermore, it can enhance cardiac function in CHF patients without elevating the... |
| 5 (MA +large) | Lin, 2024 | Meta-analysis, 20 studies, n=1,827 | Metformin and myoinositol may reduce OHSS risk in PCOS patients but did not significantly improve pregnancy outcomes. Metformin may lower OHSS risk in agonist protocol, reduce E2 levels on trigger day and increase mature oocytes... |
| 5 (MA +large) | Zhao, 2024 | Meta-analysis, 407 studies | Exercise, metformin and their combination are efficacious in improving glucose metabolism in both prediabetes and T2DM. The efficacy of exercise appears to be superior to metformin in prediabetes, but metformin appears to be... |
| 5 (MA +large) | Yi, 2024 | Meta-analysis, 25 studies, n=2,437 | Based on the efficacy and safety evaluation results, our findings suggest that a daily dosage of 750 mg of metformin may represent the optimal dose for controlling the progression from pre-diabetes to diabetes. |
| 5 (MA +large) | Harsoyo, 2024 | Meta-analysis, 413 studies, n=1,199 | Metformin was found to have an additional effect of endothelial function improvement. |
| 5 (MA +large) | Elhalag, 2024 | Meta-analysis, 10 studies, n=1,447,470 | Our study revealed no role of metformin in decreasing age-related macular degeneration risk in past or present usage. More RCTs are needed to support our findings in evaluating the actual role of metformin in age-related macular... |
| 5 (MA +large) | El-Damanawi, 2024 | Meta-analysis, 11 studies, n=8,449 | No studies reported the incidence of kidney failure. This review highlights the lack of RCTs reporting on the effects of metformin on kidney function, particularly in patients with CKD. Future research in this field requires... |
| 5 (MA +large) | Alnuaimi, 2024 | Meta-analysis, 2023 studies, n=6,058 | In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these... |
| 5 (MA +large) | Liu, 2024 | Meta-analysis, 20 studies | The results of this meta-analysis indicate that MET treatment exerts a suppressive effect on serum AMH levels in women with PCOS. It appears that a treatment duration of at least three months is required to achieve a significant... |
| 5 (MA +large) | Pakkam, 2024 | Meta-analysis, 1051 studies, n=11,589 | Our meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM. |
| 5 (MA +large) | Cigrovski Berkovic, 2024 | Meta-analysis, 13 studies, n=5,674 | T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients. Unfortunately, a few studies with heterogeneous results limited the possibility of exploring the... |
| 5 (MA +large) | Adamyan, 2024 | Meta-analysis, 280 studies, n=1,104 | Combined therapy is effective. Metformin shows superiority to the standard regimen in achieving better CR rate in patients with AEH and benefits pregnancy rates but not recurrence or live birth rates. |
| 5 (MA +large) | Haber, 2024 | Meta-analysis, 49 studies | MTF was associated with a modest weight reduction in obese nondiabetic patients. Further high-quality and better powered studies are needed to examine the impact of MTF in patients with insulin resistance and NAFLD. |
| 5 (MA +large) | Mesquita, 2024 | Meta-analysis, 27 studies, n=10 | Metformin did not reduce cancer incidence in RCTs involving subjects with overweight/obesity and/or prediabetes/diabetes. |
| 5 (MA +large) | Zhang, 2024 | Meta-analysis, 11 studies, n=8,679 | Our findings support the effectiveness and safety of MET in achieving optimal blood glucose control in GDM. These results suggest the potential for broader clinical adoption of MET in GDM management. |
| 5 (MA +large) | Melin, 2024 | Meta-analysis, 36 studies, n=10 | The choice of metformin or COCP treatment should be based on symptoms, noting some biochemical benefits from combination treatment targeting both major endocrine disturbances seen in PCOS (hyperinsulinemia and hyperandrogenism). |
| 5 (MA +large) | Wang, 2023 | Meta-analysis, n=5,440 | Our study supports the notion that GDF-15 increases the risk of severe COVID-19 in patients. However, there is no causal relationship between GDF-15 and hospitalization or susceptibility to COVID-19. |
| 5 (MA +large) | Li, 2023 | Meta-analysis, 5 studies, n=1,713,528 | Metformin use is beneficial for reducing the risk of thyroid cancer. For further investigation, more well-designed studies are still needed to elucidate the association between metformin use and the risk of thyroid cancer. |
| 5 (MA +large) | Peng, 2023 | Meta-analysis, 30 studies | SLC22A1 rs622342 and rs628031 polymorphisms were potentially associated with glycemic response to metformin. This evidence may provide novel insight into gene-oriented personalized medicine for diabetes. |
| 5 (MA +large) | Zhou, 2023 | Meta-analysis, 167 studies, n=257 | This meta-analysis provided quantitative evidence demonstrating that metformin significantly decreased AMH levels, especially for young patients and those with AMH levels at baseline higher than 4.7 ng/ml. |
| 5 (MA +large) | Hu, 2023 | Meta-analysis, 15 studies, n=3,394 | This meta-analysis indicated that metformin had no significant effect on BMD. Metformin decreased some bone turnover markers as N-terminal propeptide of type I procollagen and C-terminal telopeptide of type I collagen. But the... |
| 5 (MA +large) | Zhang, 2023 | Meta-analysis, 22 studies, n=1,698 | Saroglizatar was the most effective drug for improving NAFLD.INPLASY registration number: INPLASY202340066. |
| 5 (MA +large) | Medeiros, 2023 | Meta-analysis, 328 studies, n=171 | The synthesis showed that using metformin reduced serum Anti-Müllerian Hormone values (SMD - 0.79, 95 %CI - 1.03 to - 0.56, p < 0.001, I2 = 0 %, six studies, 299 participants, low quality of evidence). Metformin administration in... |
| 5 (MA +large) | Chen, 2023 | Meta-analysis, 11 studies, n=24,788,738 | Conclusions: Metformin may not be able to reduce the risk of BTC and improve prognosis in certain populations. Based on the limited quantity and quality of the included studies, the present results should be interpreted within... |
| 5 (MA +large) | Paridari, 2023 | Meta-analysis, 21 studies, n=1,392,809 | Low to moderate level of evidence in RCTs showed that metformin monotherapy could reduce stroke risk in type 2 diabetic patients. However, the preventive effect of metformin in stroke was not observed in patients who received a... |
| 5 (MA +large) | Fontes, 2023 | Meta-analysis, 18 studies | We showed that metformin proved to be effective in reducing total testosterone levels, and the same was observed for free androgen index (FAI) values-a measure influenced by testosterone levels. The protocol of this study was... |
| 5 (MA +large) | Zeng, 2023 | Meta-analysis, 2022 studies, n=2,190,285 | Although statin and aspirin use were associated with reduced HCC risk, only statin use was significant in subgroup analyses accounting for concurrent medications. Metformin use was not associated with reduced HCC risk. |
| 5 (MA +large) | Sheng, 2023 | Meta-analysis, 24 studies, n=4,355 | Our meta-analysis provides further evidence that metformin is a safe oral antihyperglycemic drug and has some benefits over insulin when used for the treatment of gestational diabetes, without an increased risk of short-term... |
| 5 (MA +large) | Lu, 2023 | Meta-analysis, 30 studies | Women with T2DM were more likely to be diagnosed with BC and this association was strengthened by adjusting for BMI and menopausal status. No statistically significant reduction of BC risk was observed among metformin users. |
| 5 (MA +large) | Yuan, 2022 | Meta-analysis, 2022 studies, n=5,936 | Metformin treatment significantly prolongs the OS and decreases the recurrence rate for HCC patients with T2DM after curative HCC therapy. |
| 5 (MA +large) | Unanyan, 2022 | Meta-analysis, 35 studies, n=4,668 | To our knowledge, it is the first meta-analysis that estimates inositol treatment compared to metformin. Based on our systematic review and meta-analysis, metformin seems to be a good option for improving ART outcomes in women... |
| 5 (MA +large) | Wen, 2022 | Meta-analysis, 22 studies, n=5,943 | Metformin treatment was not associated with cancer-related mortality in adults compared with placebo or no treatment. However, metformin implied beneficial effects in the PFS of the patients with reproductive system cancers but... |
| 5 (MA +large) | Nabrdalik, 2022 | Meta-analysis, 71 studies | The risk of gastrointestinal adverse events such as abdominal pain, nausea and diarrhea is higher in type 2 diabetes patients treated with metformin compared to other antidiabetic drugs. There is a higher risk of bloating and... |
| 5 (MA +large) | Luo, 2022 | Meta-analysis, 10 studies, n=229,110 | The available evidence does not support the idea that metformin reduces risk of AD, and it may, in fact, increase the risk in Asians. Further well-designed randomized controlled trials are required to understand the role played... |
| 5 (MA +large) | Liu, 2022 | Meta-analysis, 2021 studies, n=539 | The use of metformin might result in decreased BMI (kg/m2), BMI z-score, and TIDD and increased risk of hypoglycemia events and GIAEs in adolescents with T1DM. However, future studies are required to further confirm the optimal... |
| 5 (MA +large) | Hung, 2022 | Meta-analysis, 2021 studies, n=5,326 | Initial combination of metformin plus a low hypoglycemic risk antidiabetic drug may achieve better glycemic control, without a rise in hypoglycemia, in patients with untreated T2DM. |
| 5 (MA +large) | Zhao, 2022 | Meta-analysis, 17 studies, n=2,899 | The use of metformin in pregnant women with PCOS can significantly reduce maternal complications. No significant difference was observed in serious maternal adverse events. |
| 5 (MA +large) | Ding, 2022 | Meta-analysis, 11 studies, n=8,533 | Compared with metformin, vildagliptin combined with metformin could significantly reduce FPG, HbA1c and body weight. When the dose of metformin in the combination group of vildagliptin and metformin is ≥1500mg/d, the results... |
| 5 (MA +large) | Zhang, 2022 | Meta-analysis, 12 studies, n=194,792 | This systematic review and meta-analysis found that metformin use, especially long-term use, was associated with lower ND risk. However, because there was substantial heterogeneity among studies, high-quality randomized... |
| 5 (MA +large) | Ganesh, 2022 | Meta-analysis, 32 studies, n=19 | Poor outcomes in COVID-19 patients with DM can be attributed to inadequate glycaemic control and weakened immune responses. Metformin has multiple effects that can improve outcomes in patients with DM and our findings highlight a... |
| 5 (MA +large) | Li, 2022 | Meta-analysis, 35 studies, n=61,704 | Metformin use is associated with a reduction in all-cause mortality, cardiovascular mortality, incidence of coronary revascularisation, and heart failure in patients with CVD; however, metformin usage was not associated with... |
| 5 (MA +large) | Zheng, 2022 | Meta-analysis, 204 studies | All eight antihyperglycemic drug classes, taken in combination with metformin, reduced HbA1c levels; however, the effects of the agents on other outcomes varied among the classes. |
| 5 (MA +large) | Morio, 2022 | Meta-analysis, 412 studies | Metformin should be discouraged routinely in nondiabetic patients with metastatic/recurrent breast cancer. Further RCTs are needed to verify whether metformin with chemotherapy or endocrine therapy results in significant clinical... |
| 5 (MA +large) | Chae-Kim, 2021 | Meta-analysis, 271 studies, n=621 | For reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer, progestin and metformin therapy compared with progestin therapy alone is associated with lower relapse rates, and similar remission,... |
| 5 (MA +large) | Lavalle-Cobo, 2021 | Meta-analysis, 7 studies, n=11,510 | In this meta-analysis, GLP-1RAs reduced the incidence of MACE in patients with type 2 diabetes without metformin at baseline, without significant reduction in all-cause mortality and cardiovascular mortality. These results... |
| 5 (MA +large) | Yao, 2021 | Meta-analysis, 1883 studies, n=123,212 | For bladder cancer, no obvious benefits of metformin use were identified. However, subgroup analysis indicated that metformin may improve the recurrence of bladder cancer, but this improvement was only found in patients with a... |
| 5 (MA +large) | Yu, 2021 | Meta-analysis, 4533 studies | The present meta-analysis suggests that metformin may be as effective as insulin for glycemic control and is the most promising drug for the prevention of neonatal and maternal complications. |
| 5 (MA +large) | Yang, 2021 | Meta-analysis, 17 studies, n=19 | Our meta-analysis indicated that following metformin treatment might benefit the patients with T2DM, both the mortality and severity. However, patients with severe COVID-19 should be monitored closely for the development of... |
| 5 (MA +large) | Wang, 2021 | Meta-analysis, 32 studies, n=5,964 | This review suggests that metformin can decrease the incidence of perinatal complications, and it should be considered as a generally safe alternative to insulin. |
| 5 (MA +large) | Abrilla, 2021 | Meta-analysis, 2021 studies, n=2,609 | MXR was associated with statistically worse but likely clinically similar HbA1c lowering and minimal improvement of GI intolerance compared to MIR. Protocol Registration: PROSPERO (CRD42019148008). |
| 5 (MA +large) | Musa, 2021 | Meta-analysis, 38 studies, n=6,046 | Metformin is, at least, comparable to insulin for the treatment of GDM. Glibenclamide appears less favorable, in comparison to insulin, than metformin. |
| 5 (MA +large) | Li, 2021 | Meta-analysis, 167 studies | Observational evidence on metformin seems largely unreliable. Randomized evidence shows benefits for preventing diabetes and in some gynaecological and obstetrical settings. |
| 5 (MA +large) | Li, 2021 | Meta-analysis, 29 studies | The combination of metformin treatment may impose higher risk in all-cause and cardiovascular mortality. This finding, at least in part, shows no evidence for benefits of metformin in combination in terms of... |
| 5 (MA +large) | Gebrie, 2021 | Meta-analysis, 9 studies, n=10,974 | Combination therapy of metformin and sodium-glucose cotransporter-2 inhibitors is a safe and efficacious alternative to combination therapy of metformin and sulphonylureas for patients with type 2 diabetes who are at risk of... |
| 5 (MA +large) | Meng, 2021 | Meta-analysis, 2020 studies | Combined treatment with simvastatin plus metformin was better to treat PCOS than metformin alone as evidenced by significantly reduced total testosterone, LH:FSH ratio and LDL cholesterol. |
| 5 (MA +large) | Chen, 2021 | Meta-analysis, 28 studies, n=1,631 | It was the first time to quantify the effects of metformin on body weight and recommend dose and duration for metformin monotherapy and metformin combination therapy in PCOS patients. |
| 5 (MA +large) | Scheen, 2021 | Meta-analysis, 5 studies, n=24,821 | Our meta-analyses involving a larger number of trials than before have revealed that background metformin therapy has no significant influence on either the neutral impact of DPP-4is or the positive impact of SGLT2is on CV events... |
| 5 (MA +large) | Yen, 2021 | Meta-analysis, 51 studies, n=2,405 | For PCOS patients, metformin as stand-alone or adjuvant therapy was associated with improvement of acne. More randomized controlled trials are needed to validate these results. |
| 5 (MA +large) | Chang, 2021 | Meta-analysis, 2020 studies, n=8,541 | PREVENTION RELEVANCE: Meta-analyses of RCT and cohort studies showed no significant association between metformin and skin cancer, although suggestive evidence of modestly reduced skin cancer risks among metformin users was... |
| 5 (MA +large) | Zhang, 2021 | Meta-analysis, 67 studies, n=10,695,875 | Our meta-analysis indicated that metformin may be a independent protective factor for cancer risk in T2DM patients. |
| 5 (MA +large) | Jia, 2021 | Meta-analysis, 64 studies, n=37,780 | Both GLP-1RAs and SGLT-2is have their own advantages in efficacy and safety. Monotherapy is beneficial for reducing the risk of hypoglycemia. |
| 5 (MA +large) | Piera-Mardemootoo, 2021 | Meta-analysis, 16 studies, n=1,140 | This study provides the precise effects of metformin monotherapy regarding the decreases in fasting plasma glucose and glycosated hemoglobin that physician can expected in drug-naive patients with type 2 diabetes mellitus. No... |
| 5 (MA +large) | Lukito, 2020 | Meta-analysis, 9 studies, n=10,233 | The analysis showed that metformin consumption was associated with lower mortality. Randomized controlled trials are needed to confirm this finding. |
| 5 (MA +large) | Hu, 2020 | Meta-analysis, 13 studies, n=303,540 | Metformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess... |
| 5 (MA +large) | Chen, 2020 | Meta-analysis, 21 studies, n=1,885 | The present study firstly provided quantitative information for metformin effects on weight in different disease states, including patients with type 2 diabetes mellitus, patients with antipsychotic induced weight gain, patients... |
| 5 (MA +large) | Shi, 2020 | Meta-analysis, 21 studies, n=38,772 | These results suggest that metformin is associated with survival benefit in patients with PC and concurrent DM. Further randomized controlled trials and prospective studies with larger sample sizes are required to confirm our findings. |
| 5 (MA +large) | Wen, 2020 | Meta-analysis, 2020 studies, n=25,252 | This meta-analysis suggested that metformin decreased the risk of asthma-related emergency room visits for patients with concurrent asthma and diabetes. Metformin reduced the risk of asthma-related hospitalization and... |
| 5 (MA +large) | Fraison, 2020 | Meta-analysis, 44 studies, n=2,253 | In adolescent women with PCOS, we are uncertain whether there is a difference between any of the comparisons for hirsutism and adverse events due to either no evidence or very low-quality evidence. Further large well-designed... |
| 5 (MA +large) | Zhuang, 2020 | Meta-analysis, 8 studies, n=7,346 | Patients taking the DSM therapy had better effects in reducing the level of HbA1c, FPG, body weight, SBP and DBP than the DM and SM therapy. However, patients treated with DSM therapy are more likely to have hypoglycemia and... |
| 5 (MA +large) | Qian, 2020 | Meta-analysis, 25 studies, n=19,500 | SGLT2is and metformin combination therapy did not influence fracture risk compared with metformin monotherapy or other comparators in patients with T2DM. |
| 5 (MA +large) | Bagepally, 2020 | Meta-analysis, 56 studies | GLP1 agonists are a cost-effective choice compared with insulins, but not compared with DPP4i, sulfonylureas and TZDs. |
| 5 (MA +large) | Ng, 2020 | Meta-analysis, 58 studies | This meta-analysis showed that metformin use significantly reduces colorectal adenoma and cancer incidence and improves colorectal cancer outcomes. |
| 5 (MA +large) | Gnesin, 2020 | Meta-analysis, 18 studies, n=1,454 | Furthermore, 24 trials with 2369 participants are awaiting assessment. There is no clear evidence whether metformin monotherapy compared with no intervention, behaviour changing interventions or other glucose-lowering drugs... |
| 5 (MA +large) | Zhang, 2020 | Meta-analysis, 10 studies, n=254,679 | Metformin significantly improved cognitive dysfunction in patients with T2D. Sulfonylureas also improved cognitive dysfunction. Thiazolidinediones had no significant effect on cognitive dysfunction. |
| 5 (MA +large) | Sadeghi, 2020 | Meta-analysis, 38 studies, n=2,199 | However, the effect of metformin on LBM was not significant. Further studies are required to confirm these findings. |
| 5 (MA +large) | Weng, 2020 | Meta-analysis, 7 studies, n=5,731 | This meta-analysis revealed that metformin could reduce total cholesterol and LDL-c in nondiabetic adults. In addition, metformin might exert a triglyceride-lowering effect in nondiabetics with PCOS status. |
| 5 (MA +large) | Blumenberg, 2020 | Meta-analysis, 2019 studies, n=170 | Our review found higher mortality from MALA than seen in recent studies. This may be due to variation in standard medical practice both geographically and across the study interval, sample size, misidentification of MALA for... |
| 5 (MA +large) | Zhang, 2020 | Meta-analysis, 16 studies, n=1,160,254 | Our meta-analysis indicated that following metformin treatment in patients with T2DM was associated with decreased cardiovascular risk, both with the mortality and incidence. However, the heterogeneity among studies may... |
| 5 (MA +large) | Sharpe, 2019 | Meta-analysis, 41 studies, n=4,552 | Results differed by body mass index (BMI), emphasising the importance of stratifying results by BMI. No studies reported gastrointestinal side effects in this comparison. Due to the low quality of the evidence, we are uncertain... |
| 5 (MA +large) | Madsen, 2019 | Meta-analysis, 20 studies, n=6,774 | Likewise, the combination of metformin and intensive diet and exercise compared to intensive diet and exercise only neither showed an advantage or disadvantage regarding the development of T2DM (very low-quality evidence). Data... |
| 5 (MA +large) | Guo, 2019 | Meta-analysis, 41 studies, n=7,703 | Compared with insulin, glyburide had a higher increase of neonatal hypoglycemia. The use of glyburide in pregnancy for GDM women appears to be unclear. |
| 5 (MA +large) | Han, 2019 | Meta-analysis, 40 studies, n=1,066,408 | Metformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. |
| 5 (MA +large) | Hidayat, 2019 | Meta-analysis, 23 studies | The use of insulin or sulphonylureas may increase fracture risk; this risk is most likely attributed to an increased risk of hypoglycaemia-induced falls. Further confirmation by additional RCTs is required to determine whether... |
| 5 (MA +large) | Han, 2019 | Meta-analysis, 462 studies | The available evidence is, however, inconclusive given its moderate to low quality. More high-quality research is needed to assess the efficacy of a GLP-1 receptor agonist on women with PCOS. |
| 5 (MA +large) | Wen, 2019 | Meta-analysis, 80 studies, n=1,710,080 | The results suggested the metformin can be used as a potential anticarcinogenic drug for gynecological cancers' prevention, especially for Asians and cervical cancer. The question remains, still, whether metformin is beneficial... |
| 5 (MA +large) | Wang, 2019 | Meta-analysis, 20 studies | For overweight polycystic ovary syndrome patients, our evidence revealed that EE/CA and EE/SRSP combined with metformin or lifestyle changes can reduce the adverse effects on glucose and lipid metabolism of the use of oral... |
| 5 (MA +large) | Nayan, 2019 | Meta-analysis, 2017 studies, n=7,426 | There is no evidence of a statistically significant association between metformin use and any survival outcome in kidney cancer. We discuss the potential for bias in chemoprevention studies and provide recommendations to reduce... |
| 5 (MA +large) | Cai, 2019 | Meta-analysis, 71 studies | Dapagliflozin treatment was more cost-effective compared with metformin treatment for Chinese type 2 diabetes patients. However, the findings of favorable cost-effectiveness results for dapagliflozin are largely driven by the... |
| 5 (MA +large) | Hui, 2019 | Meta-analysis, 34 studies, n=8,461 | When considering the efficacy of interventions for losing weight, metformin offers clear advantages for overweight and obese populations. |
| 5 (MA +large) | Jia, 2019 | Meta-analysis, 5 studies, n=33,830 | This meta-analysis showed that repaglinide and metformin would be the most efficacious oral drugs for first-line monotherapy of T2DM. |
| 5 (MA +large) | Kalafat, 2018 | Meta-analysis, 52 studies, n=1,260 | There is a high probability that metformin use is associated with reduced HDP incidence when compared with other treatments or placebo. The small number of studies included in the analysis, the low quality of evidence and the... |
| 5 (MA +large) | Mishriky, 2018 | Meta-analysis, 26 studies | While both SGLT-2i and DPP-4i can reduce A1c, SGLT-2i causes a more robust A1c reduction and more weight loss but with more genital infections. Higher doses of SGLT-2i showed more efficacy when compared to DPP-4i; however, this... |
| 5 (MA +large) | Li, 2018 | Meta-analysis, 7 studies, n=5,143 | Incidence of hypoglycemia was significantly higher, but incidence of hyperglycemia was significantly lower in SGLT2 inhibitor group. Overall, drug-related adverse events were more common in SGLT2 group mainly due to higher... |
| 5 (MA +large) | Wang, 2018 | Meta-analysis, 25 studies, n=14 | This review revealed that, compared to DPP-4is, SGLT-2is significantly reduced HbA1c, FPG and body weight without increasing the risk of hypoglycaemia in diabetes treatment. |
| 5 (MA +large) | Jian-Yu E, 2018 | Meta-analysis, 116 studies, n=12,057 | Our findings suggest that the improved survival time of pancreatic cancer patients are associated with statin or metformin use. Due to the multiple sources of heterogeneity of the original studies, these findings should be... |
| 5 (MA +large) | Morley, 2017 | Meta-analysis, 48 studies, n=4,451 | Results differed by body mass index (BMI), emphasising the importance of stratifying results by BMI. An improvement in clinical pregnancy and ovulation suggests that clomiphene citrate remains preferable to metformin for... |
| 5 (MA +large) | Roberts, 2017 | Meta-analysis, 27 studies | The economics of preventing diabetes are complex. There is some evidence that diabetes prevention programmes are cost effective, but the evidence base to date provides few clear answers regarding design of prevention programmes... |
| 5 (MA +large) | Wang, 2017 | Meta-analysis, 216 studies | This meta-analysis showed a significant decrease of serum CRP levels, especially in obese women, but no significant changes in IL-6 levels after metformin treatment in women with PCOS. In general, the data support that early... |
| 5 (MA +large) | Meireles, 2017 | Meta-analysis, 2017 studies | Regardless the high heterogeneity of the analyzed studies, the present review suggests that adjunct metformin treatment may assist in the reversal of atypical endometrial hyperplasia to normal endometrial histology, in the... |
| 5 (MA +large) | Jung, 2017 | Meta-analysis, 10 studies, n=8,726 | Metformin use seemed to be associated with a reduced risk of colorectal adenoma, especially in high-risk populations consisting of patients with diabetes mellitus or a history of CRN, although statistical power was not achieved... |
| 5 (MA +large) | Chen, 2017 | Meta-analysis, 20 studies, n=433 | Decreased CRP levels are not associated with the status of IR and androgen in patients with PCOS. However, the quality of evidence was very low because of the limitations and inconsistency of the included studies. Therefore,... |
| 5 (MA +large) | Hou, 2017 | Meta-analysis, 7 studies, n=7,178 | This meta-analysis indicates that metformin therapy is correlated with a significant decrease in the risk of CRA and advanced adenoma in T2D patients. Further confirmatory studies are warranted. |
| 5 (MA +large) | Coyle, 2016 | Meta-analysis, 7670 studies, n=24 | Our findings suggest that metformin could be a useful adjuvant agent, with the greatest benefits seen in colorectal and prostate cancer, particularly in those receiving radical radiotherapy, and randomised, controlled trials... |
| 5 (MA +large) | Graff, 2016 | Meta-analysis, 3951 studies, n=121 | The present results suggest that orlistat leads to significant reduction in BMI/body weight in PCOS. In addition, the available evidence indicates that orlistat and metformin have similar effects in reducing BMI, HOMA,... |
| 5 (MA +large) | Wan, 2016 | Meta-analysis, 17 studies | Analyses stratified by treatment strategy showed a reduction in the risk of cancer-related mortality in patients receiving chemotherapy(for DFS: HR = 0.71, 95%CI = 0.64-0.83; for OS: HR = 0.58, 95%CI = 0.47-0.71) but not in... |
| 5 (MA +large) | Gao, 2016 | Meta-analysis, 27 studies | DPP-4 inhibitors and metformin therapy was effective and safe for T2DM patients. The glucose-lowering efficacy of DPP-4 inhibitors was same in Asian and Caucasian patients, although the effect on HOMA-β was inferior in Asian patients. |
| 5 (MA +large) | Lozano-Ortega, 2016 | Meta-analysis, 30 studies, n=28 | Only SGLT2 inhibitors and GLP-1 analogues led to a weight loss (-1.71 kg and -1.14 kg, respectively) and decrease in systolic blood pressure (SBP; -3.73 mmHg and -2.90 mmHg, respectively), while all other treatments showed either... |
| 5 (MA +large) | Shi, 2016 | Meta-analysis, 33 studies, n=1,433 | Decreased serum levels of CRP and hs-CRP may contribute to a more sensitive prediction in providing a more accurate efficacy reference in the metformin drug in T2DM patients. |
| 5 (MA +large) | Xu, 2015 | Meta-analysis, 11 studies, n=5,464 | The use of metformin in standard cancer therapy might improve both overall and cancer-specific survivals of diabetic patients with breast cancer. Diabetic patients with breast cancer receiving metformin and neoadjuvant... |
| 5 (MA +large) | Zhong, 2015 | Meta-analysis, 17 studies, n=5,874 | The three injectables had similar impact on glycemic control but other differentiating features relevant to the management of type 2 diabetes with GLP-1 RAs having the most favorable profile. |
| 5 (MA +large) | Mearns, 2015 | Meta-analysis, 20 studies | When added to metformin and a sulphonylurea, antihyperglycaemic agents had varying effects on efficacy and safety endpoints. These conclusions should be considered when clinicians choose between possible adjunctive agents. |
| 5 (MA +large) | Balsells, 2015 | Meta-analysis, 15 studies, n=2,509 | At short term, in women with gestational diabetes requiring drug treatment, glibenclamide is clearly inferior to both insulin and metformin, while metformin (plus insulin when required) performs slightly better than insulin.... |
| 5 (MA +large) | Kawalec, 2014 | Meta-analysis, 22 studies | However, we found that the SGLT-2 inhibitors were more likely to cause a genital infection. Despite some limitations, the findings of this meta-analysis indicate that DPP-4 or SGLT-2 inhibitors have favourable safety profile, and... |
| 5 (MA +large) | Zhang, 2014 | Meta-analysis, 28 studies | The findings of this study support the hypothesis that metformin improves the survival for cancer patients with concurrent diabetes, particularly for breast, colorectal, ovarian, and endometrial cancer. Further investigation is warranted. |
| 5 (MA +large) | Yin, 2013 | Meta-analysis, n=13,008 | These results suggest that metformin is the drug of choice in the treatment of patients with cancer and concurrent type 2 diabetes. |
| 5 (MA +large) | Thakkar, 2013 | Meta-analysis, 24 studies | This analysis using pooled primary data demonstrates that metformin use reduces, while sulfonylurea use may be associated with an increased cancer risk in subjects with T2DM. These findings need to be confirmed in large-scale... |
| 5 (MA +large) | Zhang, 2013 | Meta-analysis, 37 studies, n=1,535,636 | Metformin can reduce the incidence of overall cancer, liver cancer, pancreatic cancer, colorectal cancer and breast cancer as well as the mortality of overall cancer, liver cancer and breast cancer. No beneficial effect on... |
| 5 (MA +large) | Misso, 2013 | Meta-analysis, 4981 studies | However, a lack of superiority of one treatment is not evidence for equivalence, and further methodologically rigorous trials are required to determine whether there is a difference in effectiveness between metformin and placebo... |
| 5 (MA +large) | Hemmingsen, 2012 | Meta-analysis, 26 studies, n=2,286 | There was no evidence or even a trend towards improved all cause mortality or cardiovascular mortality with metformin and insulin, compared with insulin alone in type 2 diabetes. Data were limited by the severe lack of data... |
| 5 (MA +large) | Boussageon, 2012 | Meta-analysis, n=13,110 | Although metformin is considered the gold standard, its benefit/risk ratio remains uncertain. We cannot exclude a 25% reduction or a 31% increase in all-cause mortality. |
| 5 (MA +large) | Deacon, 2012 | Meta-analysis, 27 studies | Incretin-based therapy efficiently improves glycaemia when added to metformin in patients with type 2 diabetes, and within 16-30 weeks there is a more pronounced reduction in HbA1c with long-acting GLP-1 receptor agonists... |
| 5 (MA +large) | Du, 2012 | Meta-analysis, 161 studies, n=278 | This systematic review and meta-analysis suggests that pioglitazone was more suitable for treating hyperinsulinemia and insulin resistance among PCOS patients, while metformin was more effective in reducing body weight. Well... |
| 5 (MA +large) | Hirst, 2012 | Meta-analysis, 1950 studies | Evidence supports the effectiveness of metformin therapy in a clinically important lowering of HbA(1c) used as monotherapy and in combination with other therapeutic agents. There is potential for using higher doses of metformin... |
| 5 (MA +large) | Lamanna, 2011 | Meta-analysis, 35 studies, n=11 | Available evidence seems to exclude any overall harmful effect of metformin on cardiovascular risk, suggesting a possible benefit versus placebo/no treatment. The observed detrimental effect of the combination with sulphonylureas... |
| 5 (MA +large) | Phung, 2010 | Meta-analysis, 27 studies | When added to maximal metformin therapy, all noninsulin antidiabetic drugs were associated with similar HbA(1c) reductions but differed in their associations with weight gain and risk of hypoglycemia. |
| 5 (MA +large) | Creanga, 2008 | Meta-analysis, 406 studies, n=1,639 | Using all available evidence, this meta-analysis suggests that metformin increases the likelihood of ovulation and, in combination with clomiphene, increases the odds of both ovulation and pregnancy in women with polycystic ovary syndrome. |
| 5 (MA +large) | Salpeter, 2008 | Meta-analysis, 31 studies, n=4,570 | Metformin treatment in persons at risk for diabetes improves weight, lipid profiles, and insulin resistance, and reduces new-onset diabetes by 40%. The long-term effect on morbidity and mortality should be assessed in future trials. |
| 5 (MA +large) | Monami, 2008 | Meta-analysis, 27 studies | When combined with metformin, sulphonylureas and alpha-glucosidase inhibitors show a similar efficacy on HbA1c. The effects of drugs used as add-on to metformin monotherapy could be different from those observed in monotherapy. |
| 5 (MA +large) | Moll, 2007 | Meta-analysis, 27 studies | In IVF, metformin led to fewer cases of ovarian hyperstimulation syndrome (OHSS) (RR 0.33; 95% CI 0.13-0.80). This meta-analysis demonstrates that CC is still first choice therapy for women with therapy naïve PCOS. In... |
| 5 (MA +large) | Sáenz Calvo, 2005 | Meta-analysis, 29 studies | In the long term metformin reduces the risks of clinical events associated with diabetes. There are no long term clinical trials which compare alpha-glucosidase inhibitors, meglitinides, and thiazolidinediones with metformin, in... |
| 5 (MA +large) | Saenz, 2005 | Meta-analysis, 29 studies, n=5,259 | Metformin produces beneficial changes in glycaemia control, and moderated in weight, lipids, insulinaemia and diastolic blood pressure. Sulphonylureas, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, insulin, and... |
| 4 (MA) | El-Khouly, 2026 | Meta-analysis, 8 studies | In high-risk pregnancies, higher-dose vitamin D regimens were associated with lower estimated risks of preeclampsia compared with placebo; however, these findings are based on limited, heterogeneous, and partly indirect evidence... |
| 4 (MA) | Mousa, 2026 | Meta-analysis, 10 studies, n=1,159 | In this IPD meta-analysis, metformin was not associated with a reduction in GDM, but was associated with an increase in gestational age at delivery. |
| 4 (MA +large -nonRCT) | Karimi, 2026 | Meta-analysis, 29 studies | This meta-analysis indicated a potential protective effect of Metformin use in individuals with T2DM against lung cancer, with a significant risk reduction observed, particularly among long-term users and in Asian populations.... |
| Score | Study | Design, n | Finding |
|---|---|---|---|
| 5 (RCT +blind +n200) | Pistenmaa, 2026 | RCT, n=3,234 | In this long-term follow-up after a randomized trial, we found no significant associations between randomization to metformin or lifestyle intervention and lung function or respiratory symptoms. |
| 5 (RCT +blind +n200) | Nava, 2026 | RCT, n=221 | Our findings suggest that in older adults with obesity undergoing intensive lifestyle intervention, metformin does not provide additional improvement in physical function. These results support prioritising lifestyle-based... |
| 5 (RCT +blind +n200) | Salive, 2026 | RCT, n=1,999 | Among adults with prediabetes at baseline, lifestyle intervention, but not metformin, was associated with a lower burden of multimorbidity. Lifestyle programs may persistently lower the development of chronic conditions. |
| 5 (RCT +blind +n200) | Goodwin, 2026 | RCT, n=3,649 | Body mass index and blood variables did not identify subgroups with luminal or triple-negative breast cancer who benefited from metformin or those with HER2-positive breast cancer who did not benefit. |
| 5 (RCT +blind +n200) | Dokras, 2025 | RCT, n=240 | In participants with hyperandrogenic PCOS and overweight/obesity, low-dose COCPs effectively managed PCOS symptoms without increasing prevalence of MetS. Our findings challenge the current practice of using metformin alone or... |
| 5 (RCT +blind +n200) | Fleshner, 2025 | RCT, n=408 | Metformin did not reduce progression in men with low-risk PCa on AS. The observed adverse effect in obese patients merits further investigation. |
| 5 (RCT +blind +n200) | Eigl, 2025 | RCT, n=300 | Metformin did not reduce the risk of MS in patients with PCa on ADT. However, significant improvements in body weight, waist circumference, and hemoglobin A1c suggest a potential role for metformin in reducing ADT-related complications. |
| 5 (RCT +blind +n200) | Knowler, 2025 | RCT, n=3,234 | The large initial intervention effects seen in the DPP trial were followed by sustained reductions in cumulative diabetes incidence for 21 years. Intervention effects were heterogeneous according to some baseline variables. |
| 5 (RCT +blind +n200) | Heckman-Stoddard, 2025 | RCT, n=3,234 | These results may be impacted by increased nonstudy metformin usage over time due to the development of diabetes and reduced intensity of the ILS intervention over time. This study examines both metformin and ILS intervention as... |
| 5 (RCT +blind +n200) | Bae-Jump, 2025 | RCT, n=2,017 | The hazard ratios for PFS and OS endpoints was not sufficiently decreased with the addition of metformin to PC to justify continuing the trial. |
| 5 (RCT +blind +n200) | Pasanisi, 2025 | RCT, n=1,442 | The use of 1,700 mg/day MET is effective to prevent diabetes in people selected on the basis of metabolic syndrome. |
| 5 (RCT +blind +n200) | Patel, 2024 | RCT, n=831 | Among parturients with early gestational or pre-existing type 2 diabetes, the addition of metformin to insulin was not associated with lower odds of preterm preeclampsia or with serum biomarkers associated with cardiovascular disease risk. |
| 5 (RCT +blind +n200) | Johansson, 2024 | RCT, n=333 | Supportive healthy lifestyle programs combined with metformin to achieve maximal risk reduction among BC cancer survivors are recommended, especially for those with obesity in menopause. |
| 5 (RCT +blind +n200) | Goodwin, 2023 | RCT, n=3,649 | These included 48 contralateral invasive breast cancers (27 metformin v 21 placebo), HR, 1.29; 95% CI, 0.72 to 2.27; P = .40 and 136 new nonbreast primary cancers (75 metformin v 61 placebo), HR, 1.24; 95% CI, 0.88 to 1.74; P =... |
| 5 (RCT +blind +n200) | Garrib, 2023 | RCT, n=364 | Blood glucose decreased over time in both the metformin and placebo arms during the trial but did not differ significantly between the arms at 12 months of follow up. Metformin therapy was found to be safe for use in individuals... |
| 5 (RCT +blind +n200) | Kennedy, 2023 | RCT, n=514 | There was no significant impact of metformin use on pembrolizumab efficacy in resected high-risk stage III melanoma. However, larger studies or pooled analyses are needed, particularly to explore a possible effect of metformin in... |
| 5 (RCT +blind +n200) | Hershman, 2023 | RCT, n=2,521 | While non-adherence was higher among patients on metformin, it was still considerable among patients on placebo. Reassuringly, treatment arm allocation did not impact ET adherence. |
| 5 (RCT +blind +n200) | Orchard, 2023 | RCT, n=2,045 | In community-dwelling older adults with diabetes, metformin use was associated with reduced cancer incidence. Increased cancer mortality risk in metformin users randomized to aspirin warrants further investigation. |
| 5 (RCT +blind +n200) | Usmani, 2023 | RCT, n=2,019 | Men receiving radical RT and ADT gained weight and had increases in waist circumference over time that metformin did not significantly mitigate. Although this study did not observe any preventive effect of metformin on the... |
| 5 (RCT +blind +n200) | Goodwin, 2022 | RCT, n=1,824 | Among patients with high-risk operable breast cancer without diabetes, the addition of metformin vs placebo to standard breast cancer treatment did not significantly improve invasive disease-free survival. |
| 5 (RCT +blind +n200) | Goldberg, 2022 | RCT, n=3,234 | Neither metformin nor lifestyle reduced major cardiovascular events in DPPOS over 21 years despite long-term prevention of diabetes. Provision of group lifestyle intervention to all, extensive out-of-study use of statin and... |
| 5 (RCT +blind +n200) | Wilson, 2022 | RCT, n=302 | Within the limitations of post-hoc sub-analyses, metformin and statins are associated with a prolonged OS and increased PSA-RR, particularly in combination with AAP. |
| 5 (RCT +blind +n200) | Stultiens, 2022 | RCT, n=390 | In this post-hoc analysis of a 4.3-year randomized controlled trial, metformin did not exert a clinically relevant effect on cardiac troponin I and cardiac troponin T levels when compared to placebo. Cardioprotective effects of... |
| 5 (RCT +blind +n200) | Maxwell, 2022 | RCT, n=1,762 | Some loci are directly associated with incident diabetes, and others are rQTL and modify a trait's relationship with diabetes (2 diabetes/glucose, 2 diabetes/insulin, 1 diabetes/IGI). rs3197999, an ISI/insulin rQTL, is a possible... |
| 5 (RCT +blind +n200) | Schwartz, 2021 | RCT, n=3,234 | In a cohort at high risk of diabetes, lifestyle intervention or metformin did not appear to have long-term negative effects on BMD. Potential positive effects of metformin on bone warrant further research. |