J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website https://www.jofem.org

Review

Volume 12, Number 6, December 2022, pages 161-167

Protective Effect of Metformin on Venous Thrombosis in Diabetic Patients: Findings From a Systematic Review

**Table 1.** Characteristics of the Included Studies in the Systematic Review (n = 6)
Study name	Year	Study design	Setting	Sample size	Age	Gender
Hussein et al [11]	2021	Cross-sectional study	Khartum-Sudan	96	55.4 years	55.2% females and 44.8% males
Aleidan [12]	2020	A prospective cohort study	Saudi Arabia	277	70 ± 4 years	52% were males
Lin et al [13]	2017	Population-based cohort study	Taiwan	907,277	57.5 ± 12.3, 57.5 ± 14.4 years, and 31.9 ± 19.7 in branch retinal occlusion group (BRVO), central retinal vein occlusion group (CRVO), and control group, respectively	48.8% in BRVO, 53.8% in CRVO, and 50.9% males in the control group
Lu et al [14]	2014	A non-randomized, pair-matched cohort study	Taiwan	14,945	57.70 ± 12.55 years	53.1% males in the metformin group and 52.6% in the control group
Grant et al [15]	1991	Randomized controlled trial	NR	38	NR	NR
Ersoy et al [16]	2008	Prospective follow-up study	Turkey	24	50.5 ± 1.5 years	62.5% females

Table 1. Characteristics of the Included Studies in the Systematic Review (n = 6)

Study name

Year

Study design

Setting

Sample size

Age

Gender

Hussein et al [11]

2021

Cross-sectional study

Khartum-Sudan

55.4 years

55.2% females and 44.8% males

Aleidan [12]

2020

A prospective cohort study

Saudi Arabia

277

70 ± 4 years

52% were males

Lin et al [13]

2017

Population-based cohort study

Taiwan

907,277

57.5 ± 12.3, 57.5 ± 14.4 years, and 31.9 ± 19.7 in branch retinal occlusion group (BRVO), central retinal vein occlusion group (CRVO), and control group, respectively

48.8% in BRVO, 53.8% in CRVO, and 50.9% males in the control group

Lu et al [14]

2014

A non-randomized, pair-matched cohort study

Taiwan

14,945

57.70 ± 12.55 years

53.1% males in the metformin group and 52.6% in the control group

Grant et al [15]

1991

Randomized controlled trial

Ersoy et al [16]

2008

Prospective follow-up study

Turkey

50.5 ± 1.5 years

62.5% females

**Table 2.** Summary of Findings From the Included Studies in the Systematic Review (n = 6)
Study name and author	Key findings	Summary of findings
HR: hazard ratio; CI: confidence interval.
Hussein et al [11]	Both metformin and glimperide reduced the platelet indices; however, metformin had much greater effect than glimperide	Metformin had much greater effect on platelet indices than glimperide
Aleidan [12]	Metformin reduced the risk of venous thrombosis in the multivariable regression (HR: 0.16, 95% CI: 0.08 - 0.33) among elderly patients	Metformin may protect the venous thrombosis in elderly
Lin et al [13]	Metformin reduced the risk of retinal vein occlusion by 54% after adjusting for demographic and clinical factors (HR: 0.46, 95% CI: 0.30 - 0.71).	Metformin is beneficial against retinal vein occlusion in diabetic patients
Lu et al [14]	-Out of 7,167 patients given metformin, 0.21% developed deep venous thrombosis after being followed for about 3.74 years and 0.56% from the control group. -Patients who received metformin were 58% less likely to develop venous thrombosis than those who did not receive metformin. (HR: 0.42, 95% CI: 0.240 - 0.758)	Metformin is protective against deep venous thrombosis in diabetic patients
Grant et al [15]	In the metformin group, basal and post-venous occlusion plasminogen activator inhibitor 1-antigen fell after 3 weeks (P < 0.001) without any change in these concentrations in the placebo group.	Metformin reduces the venous occlusion among diabetic patients
Ersoy et al [16]	After 4 weeks of follow-up, metformin was found to improve endothelial function and prevent thrombus formation. However, there was no effect on chronic subclinical vascular formation among obese insulin-resistant diabetic individuals.	Metformin reduced the formation of plasminogen activator inhibitors and vascular endothelial growth factors.

Table 2. Summary of Findings From the Included Studies in the Systematic Review (n = 6)

Study name and author

Key findings

Summary of findings

HR: hazard ratio; CI: confidence interval.

Hussein et al [11]

Both metformin and glimperide reduced the platelet indices; however, metformin had much greater effect than glimperide

Metformin had much greater effect on platelet indices than glimperide

Aleidan [12]

Metformin reduced the risk of venous thrombosis in the multivariable regression (HR: 0.16, 95% CI: 0.08 - 0.33) among elderly patients

Metformin may protect the venous thrombosis in elderly

Lin et al [13]

Metformin reduced the risk of retinal vein occlusion by 54% after adjusting for demographic and clinical factors (HR: 0.46, 95% CI: 0.30 - 0.71).

Metformin is beneficial against retinal vein occlusion in diabetic patients

Lu et al [14]

-Out of 7,167 patients given metformin, 0.21% developed deep venous thrombosis after being followed for about 3.74 years and 0.56% from the control group. -Patients who received metformin were 58% less likely to develop venous thrombosis than those who did not receive metformin. (HR: 0.42, 95% CI: 0.240 - 0.758)

Metformin is protective against deep venous thrombosis in diabetic patients

Grant et al [15]

In the metformin group, basal and post-venous occlusion plasminogen activator inhibitor 1-antigen fell after 3 weeks (P < 0.001) without any change in these concentrations in the placebo group.

Metformin reduces the venous occlusion among diabetic patients

Ersoy et al [16]

After 4 weeks of follow-up, metformin was found to improve endothelial function and prevent thrombus formation. However, there was no effect on chronic subclinical vascular formation among obese insulin-resistant diabetic individuals.

Metformin reduced the formation of plasminogen activator inhibitors and vascular endothelial growth factors.