Association of the Reduced Function Met420del Polymorphism of SLC22A1 with Metformin-Induced Gastrointestinal Intolerance in Ethiopian Patients with Type 2 Diabetes Mellitus

Figures & data

Figure 1 Allelic discrimination plot for the delGAT/GAT polymorphic SNP rs72552763.

Table 1 General Characteristics of the Metformin Intolerance Study Participants (n = 47)

Variable	Tolerant to Metformin		Metformin Intolerant		p-value
Age at diagnosis (years) (Median, IQR)	48.0 (43.0–59.0)		47.0 (42.5 −56.0)		0.690
BMI (Kg/m2) (Median, IQR)	31.25 (28.10–33.65)		29.50 (28.30–31.95)		0.430
Baseline FBG* (mg/dl) (Median, IQR)	203.5 (152.75–239.5)		176 (145.5–288.0)		0.846
Baseline HbA1c* (%)(Median, IQR)	9.0 (7.75–11.03)		10.0 (9.0–11.0)		0.283
Metformin daily dose in mg (Median, IQR)	2000 (2000 −2000)		1000 (1000 −1500)		0.0001
Physical activity	Active %	Inactive %	Active %	Inactive %	0.010
	83.33	16.67	47.83	52.17
Sex	Male %	Female %	Male %	Female %	0.037
	45.83	54.17	17.39	82.61

Notes: *: Estimated from number of participants of less than 47.

Abbreviations: FBG, Fasting blood glucose; HbA1c, Hemoglobin A1C; IQR, Inter quartile range.

Figure 2 Independent-Samples Mann–Whitney U-test between metformin tolerant and intolerant groups on their baseline FBG (panel (A) and HbA1c levels (panel (B).

Table 2 Genotype and Allele Frequency Distribution of the rs72552763 Polymorphism Across Intolerance Study Participants (n = 47)

SNP of Interest	Genotypes and Alleles of the SNP	Intolerance Study Group		Allele/genotype Frequency (%)
		Tolerant(N)	Non Tolerant(N)
Met420del SNP of the SLC22A1 gene (rs72552763)	del_del genotype	0	0	0
	del_G genotype	5	4	19.15
	G_G genotype	19	19	80.85
	del-allele	5	4	9.60
	G-allele	43	42	90.40

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

Table 3 Logistic Regression Analysis on the Predictors of Metformin Intolerance Among Study Participants (n = 47)

Predictor Factors	Univariate Analysis
Genotypes of rs72552763	COR (95% CI)	p-value
G_G genotype	1
del_G genotype	0.8 (0.186–3.446)	0.765
Age	0.988 (0.928–1.050)	0.690
Sex(Female)	4.019 (1.048–15.416)	0.043
Physical Inactivity	5.455 (1.414–21.035)	0.014

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

Table 4 Chi-Square Test Analysis on the Effect of the Alleles of the rs72552763 Polymorphism on Metformin Intolerance Among Study Participants (n = 47)

Alleles of rs72552763	OR (95% CI)	p-value
G_ allele	1
del_allele	0.835 (0.239–2.917)	0.777

Abbreviations: OR, odds ratio; G, GAT; del, deletion.