Table 6.

Meta‐analysis results for the effects of individual single‐nucleotide polymorphisms in the subgroups of patients homozygous for the wild‐type or variant allele of possible confounding single‐nucleotide polymorphisms ‐ interactions between metformin kidney transporters ‐ monotherapy group

Subgroup	SNP	Effect allele	No. of studies	No. of patients	Beta	SE	P value	I2	P(Q)
OCT2 A270S wt/wt	MATE1 rs2289669	A	7	3,869	0.008	0.018	0.673	41.9	0.112
	MATE1 rs2252281	C	5	1,835	‐0.008	0.027	0.756	0.0	0.964
	MATE2 rs12943590	A	7	3,176	‐0.011	0.023	0.642	0.0	0.481
	OCTN1 T306I	T	7	3,642	0.030	0.019	0.118	0.0	0.660
	OCTN1 L503F	T	5	3,437	‐0.040	0.019	0.034	0.0	0.720
OCT2 A270S v/v	MATE1 rs2289669	A	3	59	0.045	0.210	0.831	0.0	0.950
	MATE1 rs2252281	C	2	35	0.575	0.175	0.001	31.8	0.226
	MATE2 rs12943590	A	3	48	0.170	0.337	0.615	0.0	0.557
	OCTN1 T306I	T	3	51	0.164	0.212	0.440	34.6	0.217
	OCTN1 L503F	T	3	50	‐0.017	0.206	0.934	20.3	0.285
MATE1 rs2289669 wt/wt	OCT2 A270S	T	7	1,598	0.021	0.042	0.613	0.0	0.568
	MATE2 rs12943590	A	7	1,288	‐0.066	0.071	0.347	58.9	0.024
	OCTN1 T306I	T	7	1,412	0.044	0.054	0.418	63.4	0.012
	OCTN1 L503F	T	5	1,328	‐0.069	0.029	0.015	0.0	0.884
MATE1 rs2289669 v/v	OCT2 A270S	T	6	495	‐0.066	0.146	0.655	65.0	0.014
	MATE2 rs12943590	A	7	363	0.065	0.052	0.215	0.0	0.529
	OCTN1 T306I	T	7	410	0.138	0.053	0.009	6.4	0.379
	OCTN1 L503F	T	5	365	‐0.156	0.055	0.004	0.0	0.612
MATE1 rs2252281 wt/wt	OCT2 A270S	T	5	862	‐0.014	0.056	0.802	0.0	0.942
	MATE2 rs12943590	A	5	720	0.006	0.046	0.902	9.2	0.354
	OCTN1 T306I	T	5	726	‐0.037	0.042	0.382	47.5	0.107
	OCTN1 L503F	T	4	662	‐0.017	0.046	0.711	19.9	0.290
MATE1 rs2252281 v/v	OCT2 A270S	T	4	329	0.129	0.076	0.087	0.0	0.592
	MATE2 rs12943590	A	5	276	‐0.042	0.061	0.494	0.0	0.829
	OCTN1 T306I	T	5	283	0.013	0.067	0.853	22.1	0.274
	OCTN1 L503F	T	4	262	‐0.011	0.074	0.884	0.0	0.650
MATE2 rs12943590 wt/wt	OCT2 A270S	T	7	1,964	0.001	0.036	0.978	22.4	0.259
	MATE1 rs2289669	A	7	1,980	‐0.010	0.023	0.673	0.0	0.454
	MATE1 rs2252281	C	5	1,014	0.051	0.034	0.138	0.0	0.661
	OCTN1 T306I	T	7	1,828	0.043	0.026	0.095	39.7	0.127
	OCTN1 L503F	T	5	1,636	‐0.050	0.027	0.062	26.4	0.246
MATE2 rs12943590 v/v	OCT2 A270S	T	7	298	‐0.017	0.088	0.849	0.0	0.830
	MATE1 rs2289669	A	7	300	0.183	0.115	0.112	51.3	0.055
	MATE1 rs2252281	C	5	139	0.089	0.097	0.357	0.0	0.534
	OCTN1 T306I	T	7	279	‐0.071	0.056	0.203	0.0	0.744
	OCTN1 L503F	T	5	241	0.080	0.058	0.168	0.0	0.455
OCTN1 T306I wt/wt	OCT2 A270S	T	7	1,806	0.081	0.041	0.048	0.0	0.557
	MATE1 rs2289669	A	7	1,728	‐0.020	0.028	0.469	0.0	0.554
	MATE1 rs2252281	C	5	827	‐0.001	0.040	0.976	35.2	0.187
	MATE2 rs12943590	A	7	1,426	0.018	0.033	0.581	0.0	0.630
OCTN1 T306I v/v	OCT2 A270S	T	6	634	‐0.017	0.067	0.803	31.7	0.198
	MATE1 rs2289669	A	7	609	‐0.023	0.040	0.571	25.7	0.232
	MATE1 rs2252281	C	5	267	0.049	0.122	0.690	63.7	0.027
	MATE2 rs12943590	A	7	541	‐0.145	0.094	0.121	63.1	0.012
OCTN1 L503F wt/wt	OCT2 A270S	T	5	1,367	‐0.040	0.047	0.394	41.8	0.143
	MATE1 rs2289669	A	5	1,274	‐0.019	0.031	0.548	0.0	0.724
	MATE1 rs2252281	C	4	583	‐0.059	0.063	0.344	42.2	0.158
	MATE2 rs12943590	A	5	1,114	‐0.049	0.057	0.394	53.5	0.072
OCTN1 L503F v/v	OCT2 A270S	T	5	816	0.106	0.063	0.095	40.2	0.153
	MATE1 rs2289669	A	5	768	‐0.042	0.045	0.354	0.0	0.982
	MATE1 rs2252281	C	4	337	0.017	0.065	0.793	5.6	0.365
	MATE2 rs12943590	A	5	584	0.031	0.053	0.561	0.0	0.857

A positive beta is a greater glycemic response to metformin associated with the effect allele.

I², heterogeneity index; MATE, multidrug and toxin extrusion transporter; OCT1, organic cation transporter 1; P(Q), P value for Cochrane's Q statistic; SNP, single‐nucleotide polymorphism; v/v, homozygous variant allele carriers; wt/wt, homozygous wild‐type allele carriers.