Association of Met420del Variant of Metformin Transporter Gene SLC22A1 with Metformin Treatment Response in Ethiopian Patients with Type 2 Diabetes

Figures & data

Table 1 Baseline and Treatment Characteristics of the Study Participants (n = 86)

Variable	Metformin Responder		Metformin Non-Responder		p-value
Age at diagnosis (years) (Median, IQR)	50.5 (40.0–56.0)		45.0 (40.0–50.0)		0.07
BMI (Kg/m2) (Median, IQR)	30.38 (26.77–32.90)		31.13 (27.95–33.25)		0.29
Baseline HbA1c (%)(Median, IQR)	8.05 (7.00–9.20)		8.00 (8.00–9.00)		0.93
Baseline Fasting glucose (mg/dl) (Median, IQR)	159.50 (138.00–192.00)		178.00 (149.50–203.00)		0.06
Baseline Triglyceride (mg/dl) (Median, IQR)	143.95 (96.50–210.45)		148.50 (103.50–209.00)		0.70
Baseline HDL (mg/dl) (Median, IQR)	42.00 (35.25–50.70)		43.10 (38.05–46.15)		0.89
Metformin daily dose in mg (Median, IQR)	1000 (1000–2000)		1000 (1000–2000)		0.59
Physical activity	Active %	Inactive %	Active %	Inactive %	0.53
	78.57	21.42	72.72	27.27
Sex	Male %	Female %	Male %	Female %	0.70
	51.61	47.27	48.39	52.73

Table 2 Genotype and Allele Frequency Distribution of rs72552763 SNP Across the Study Participants (n = 86)

rs72552763 SNP	Response Study Group		Allele Frequency
	Non-Responder (N)	Responder (N)
del_del genotype	1	0
del_G genotype	4	10
G_G genotype	39	32
del-allele	6	10	9.3%
G-allele	82	74	90.7%

Abbreviations: N, frequency; del_del, deletion_deletion; G_G, GAT_GAT; del_G, deletion_GAT.

Table 3 Logistic Regression Analysis for Predictor of Metformin Response Among the Study Participants (n = 85)

Predictor Factors	Univariate Analysis		Multivariate Analysis
Genotypes of Met420del Variant of SLC22A1 Gene (rs72552763)	COR (95% CI)	p-value	AOR (95% CI)	p-value
G_G genotype	1		1
del_G genotype	3.047 (0.873–10.637)	0.081	3.675 (1.005–13.436)	0.049
Age	1.042 (0.993–1.093)	0.094	1.051 (0.999–1.106)	0.052
Baseline FBG	0.994 (0.986–1.002)	0.125
BMI	0.934 (0.844–1.033)	0.183	0.904 (0.808–1.012)	0.079

Abbreviations: COR, crude odds ratio; AOR, adjusted odds ratio; G_G, GAT_GAT; del_G, deletion_GAT.

Figure 1 Independent Samples Mann–Whitney U-test between genotypes of Met420del variant of SLC22A1gene (rs72552763) and absolute reductions in HbA1C (A) and in FBG (B) following three months of metformin treatment.

Figure 2 Independent Samples Mann–Whitney U-test between genotypes of Met420del variant of SLC22A1gene (rs72552763) and median HbA1c (A) and FBG (B) levels following three months of metformin treatment.

Table 4 Logistic Regression Analysis for Predictor of Glycemic Control Among the Study Participants (n = 85)

Predictor Factors	Univariate Analysis		Multivariate Analysis
Genotypes of Met420del Variant of SLC22A1 Gene (rs72552763)	COR (95% CI)	p-value	AOR (95% CI)	p-value
G_G genotype	1		1
del_G genotype	3.312 (1.001–10.961)	0.05	3.911 (0.995–15.376)	0.051
Metformin daily dose in mg	0.999 (0.998–1)	0.087
Baseline fasting glucose	0.982 (0.970–0.994)	0.003
Baseline HbA1c	0.500 (0.331–0.756)	0.001	0.478 (0.305–0.751)	0.001
BMI	0.900 (0.806–1.006)	0.063	0.847 (0.740–0.970)	0.016

Abbreviations: COR, crude odds ratio; AOR, adjusted odds ratio; G_G, GAT_GAT; del_G, deletion_GAT.