Online first
Published online: 2024-06-07

open access

Page views 47
Article views/downloads 32
Get Citation

Connect on Social Media

Connect on Social Media

Metformin for the Prevention of Prediabetes Progression to Type 2 Diabetes: A Systematic Review and Meta-Analysis

Samit Ghosal1, Surekha Tippisetty2, Subhadra Polisetti2, Krishna G. Seshadri3


Objective: The aim of this meta-analysis was to explore the effectiveness of metformin in retarding the progression of pre-diabetes to type 2 diabetes (T2D). Materials and methods: A web-based search was conducted using the Cochrane Library identifying ten citations for analysis. In the pre-analysis stage, outlier detection was carried out using funnel plots,
culprit citations identified using Byjat plot and influence analysis. The meta-analysis was conducted using a random-effects model using relative-risk (RR) as the effect-size and prediction interval (PI) as the indicator of heterogeneity. The RR was calculated by comparing the metformin and the control arm [lifestyle modification (LSM)/placebo]. R studio (2022.07.1, Build 554) software was used for analysis. Results: A total of 8869 patients with pre-diabetes were included in the meta-analysis, with 4328 patients in the metformin arm and 4541 in the control arm (LSM/placebo). There was a 22% RR reduction with metformin compared to LSM/placebo with a 95% CI of 0.71–0.86. No heterogeneity was detected in the summary effect size (PI: 0.69–0.88). Subgroup analysis using the dose of metformin (low versus high) did not influence the
outcome (p = 0.39) Conclusions: The addition of metformin to intensive LSM is an effective value addition in patients with pre-diabetes at high-risk of progression to T2D.

Article available in PDF format

View PDF Download PDF file


  1. GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023; 402(10397): 203–234.
  2. Wilmot E, Idris I. Early onset type 2 diabetes: risk factors, clinical impact and management. Ther Adv Chronic Dis. 2014; 5(6): 234–244.
  3. Hillier TA, Pedula KL. Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care. 2003; 26(11): 2999–3005.
  4. Rooney MR, Fang M, Ogurtsova K, et al. Global Prevalence of Prediabetes. Diabetes Care. 2023; 46(7): 1388–1394.
  5. Management of obesity. A national clinical guideline. Scottish Intercollegiate Guidelines Network. 2010. (9.11.2023).
  6. Ackermann RT, Edelstein SL, Narayan KM, et al. Diabetes Prevention Program Research Group. Changes in health state utilities with changes in body mass in the Diabetes Prevention Program. Obesity (Silver Spring). 2009; 17(12): 2176–2181.
  7. Davies MJ, Gray LJ, Troughton J, et al. Let's Prevent Diabetes Team. A community based primary prevention programme for type 2 diabetes integrating identification and lifestyle intervention for prevention: the Let's Prevent Diabetes cluster randomised controlled trial. Prev Med. 2016; 84: 48–56.
  8. Hostalek U, Gwilt M, Hildemann S. Therapeutic Use of Metformin in Prediabetes and Diabetes Prevention. Drugs. 2015; 75(10): 1071–1094.
  9. Lily M, Godwin M. Treating prediabetes with metformin: systematic review and meta-analysis. Can Fam Physician. 2009; 55(4): 363–369.
  10. Patel D, Ayesha IE, Monson NR, et al. The Effectiveness of Metformin in Diabetes Prevention: A Systematic Review and Meta-Analysis. Cureus. 2023; 15(9): e46108.
  11. The protocol for this systematic review was registered on INPLASY (ID: INPLASY202410050) and is available in full on
  12. Iqbal Hydrie MZ, Basit A, Shera AS, et al. Effect of intervention in subjects with high risk of diabetes mellitus in pakistan. J Nutr Metab. 2012; 2012: 867604.
  13. Orchard TJ, Temprosa M, Goldberg R, et al. Diabetes Prevention Program Research Group. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med. 2005; 142(8): 611–619.
  14. Li CL, Pan CY, Lu JM, et al. Effect of metformin on patients with impaired glucose tolerance. Diabet Med. 1999; 16(6): 477–481.
  15. Ramachandran A, Snehalatha C, Mary S, et al. Indian Diabetes Prevention Programme (IDPP). The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia. 2006; 49(2): 289–297.
  16. O'Brien MJ, Whitaker RC, Yu D, et al. The comparative efficacy of lifestyle intervention and metformin by educational attainment in the Diabetes Prevention Program. Prev Med. 2015; 77: 125–130.
  17. Sussman JB, Kent DM, Nelson JP, et al. Improving diabetes prevention with benefit based tailored treatment: risk based reanalysis of Diabetes Prevention Program. BMJ. 2015; 350: h454.
  18. Weber MB, Ranjani H, Staimez LR, et al. The Stepwise Approach to Diabetes Prevention: Results From the D-CLIP Randomized Controlled Trial. Diabetes Care. 2016; 39(10): 1760–1767.
  19. Ratner RE, Christophi CA, Metzger BE, et al. Diabetes Prevention Program Research Group. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab. 2008; 93(12): 4774–4779.
  20. Knowler WC, Barrett-Connor E, Fowler SE, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002; 346(6): 393–403.
  21. Andreadis EA, Katsanou PM, Georgiopoulos DX, et al. The effect of metformin on the incidence of type 2 diabetes mellitus and cardiovascular disease risk factors in overweight and obese subjects--the Carmos study. Exp Clin Endocrinol Diabetes. 2009; 117(4): 175–180.
  22. Engberg S, Vistisen D, Lau C, et al. Progression to impaired glucose regulation and diabetes in the population-based Inter99 study. Diabetes Care. 2009; 32(4): 606–611.
  23. Zhang X, Gregg EW, Williamson DF, et al. A1C level and future risk of diabetes: a systematic review. Diabetes Care. 2010; 33(7): 1665–1673.
  24. Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin Nutr. 2005; 82(1 Suppl): 222S–225S.
  25. Herman WH, Ratner RE. Metformin Should Be Used to Treat Prediabetes in Selected Individuals. Diabetes Care. 2020; 43(9): 1988–1990.
  26. Lily M, Godwin M. Treating prediabetes with metformin: systematic review and meta-analysis. Can Fam Physician. 2009; 55(4): 363–369.
  27. Patel D, Ayesha IE, Monson NR, et al. The Effectiveness of Metformin in Diabetes Prevention: A Systematic Review and Meta-Analysis. Cureus. 2023; 15(9): e46108.
  28. Zinman B, Harris SB, Neuman J, et al. Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Lancet. 2010; 376(9735): 103–111.