Table 2.

Genetic causal effect of metformin use on potential mediators

Potential mediators	GWAS identifier/reference	Beta1	Lo_95CI	Up_95CI	P1_value
BMI	ebi-a-GCST006802 [45]	− 4.00E−01	− 1.51E+00	7.10E−01	4.80E−01
Weight	ukb-b-11842	− 1.72E−01	− 2.02E+00	1.68E+00	8.55E−01
Waist circumference	ieu-a-67 [46]	5.12E−01	− 1.70E+00	2.73E+00	6.50E−01
ASATV	ebi-a-GCST90016672 [47]	− 2.40E−01	− 2.56E+00	2.08E+00	8.40E−01
VATV	ebi-a-GCST90016671 [47]	2.41E−01	− 1.61E+00	2.09E+00	7.99E−01
Whole body fat-free mass	ukb-b-13354	− 6.68E−02	− 1.32E+00	1.19E+00	9.17E−01
Body fat percentage	ukb-b-8909	− 1.82E−01	− 1.45E+00	1.08E+00	7.78E−01
WBC	ebi-a-GCST004610 [48]	− 1.21E−01	− 1.05E+00	8.11E−01	7.99E−01
CRP	ieu-b-4764	− 1.99E−01	− 1.35E+00	9.52E−01	7.35E−01
HDL cholesterol	ieu-b-109 [49]	− 2.38E+00	− 4.40E+00	− 3.62E−01	2.08E−02*
LDL cholesterol	ieu-b-5089	− 2.37E+00	− 3.21E+00	− 1.54E+00	2.38E−08*
Total cholesterol	ieu-a-301 [50]	− 6.69E−01	− 3.02E+00	1.68E+00	5.77E−01
SHBG	ebi-a-GCST90012111 [51]	− 1.50E+00	− 2.08E+00	− 9.24E−01	3.57E−07*
Total testosterone	ebi-a-GCST90012114 [51]	− 6.04E−01	− 9.99E−01	− 2.08E−01	2.76E−03*
Bioavailable testosterone	ebi-a-GCST90012102 [51]	9.28E−01	3.35E−01	1.52E+00	2.15E−03*
Estradiol levels	ebi-a-GCST90012105 [51]	− 1.23E−01	− 2.32E−01	− 1.31E−02	2.82E−02*
Fasting insulin	ebi-a-GCST90002238 [52]	− 3.85E−01	− 1.34E+00	5.68E−01	4.28E−01
Fasting glucose	ebi-a-GCST005186 [53]	2.65E+00	1.06E+00	4.23E+00	1.06E−03*
HbA1c	ieu-b-104 [54]	− 3.96E−01	− 9.88E−01	1.97E−01	1.90E−01
Telomere length	ieu-b-4879	− 6.25E−03	− 4.43E−01	4.30E−01	9.78E−01

All the results above were derived from the IVW method.

*P1_value < 0.05; Lo_95CI, the lower margin of beta 1’s 95% confidence interval; Up_95CI, the upper margin of beta 1’s 95% confidence interval; SHBG,Sex hormone-binding globulin; VATV, Visceral adipose tissue volume; ASATV, Abdominal subcutaneous adipose tissue volume; HDL, high-density lipoprotein; LDL, low-density lipoprotein; WBC, White blood cell