Glucagon-like-1 receptor agonists and sodium/glucose cotransporter-2 inhibitors combination—are we exploiting their full potential in a real life setting?

Table 1 Baseline characteristics of subjects at the time of therapy initiation

	Mean	SD	Median	Minimum	Maximum	n
Age, yr	62.12	9.49	63	37	86	200
Duration of diabetes, yr	11.67	6.18	11	1	43	196
HbA1c, %	8.32	1.26	8.20	5.60	13.60	200
FPG, mmol/L	9.82	2.88	9.60	3.40	20.30	126
PPG, mmol/L	11.17	3.23	10.90	4.50	24.30	145
Urea, mmol/L	6.38	1.83	6.10	2.80	11.80	89
Creatinine, mmol/L	73.82	20.41	71.00	29.00	163.00	159
eGFR, mL/min per 1.73 m2	85.88	19.27	90.00	28.00	125.00	128
Albuminuria, mg/L	35.52	62.49	13.60	2	418	62
Cholesterol, mmol/L	4.89	1.21	4.80	2.60	9.50	144
HDL, mmol/L	1.24	0.51	1.15	0.60	5.60	151
LDL, mmol/L	2.60	0.97	2.50	0.80	5.30	146
Triglycerides	2.41	1.38	2.00	0.70	8.60	159
BMI	39.41	5.49	37.90	30.00	69.00	193

BMI: Body mass index; eGFR: Estimated glomerular filtration rate; FPG: Fasting plasma glucose; HbA1c: Hemoglobin A1c; HDL: High-density lipoprotein cholesterol; LDL: Low-density lipoprotein cholesterol; PPG: Prandial plasma glucose; SD: Standard deviation.

Table 2 Differences in baseline parameters between three therapy groups

	Mean	SD	n	F ratio/Kruskal-Wallis	P value
HbA1c, %
SGLT-2i	8.09	1.07	48	6.436	0.002
GLP-1RA	8.07	1.08	76
Simultaneous	8.72	1.45	76
Total	8.32	1.26	200
FPG, mmol/L
SGLT-2i	8.75	2.17	35		0.001
GLP-1RA	9.44	2.43	55
Simultaneous	11.43	3.45	36
Total	11.17	3.23	145
BMI, kg/m2
SGLT-2i	38.18	3.60	47		0.045
GLP-1RA	38.74	4.75	70
Simultaneous	40.80	6.72	76
Total	39.41	5.49	193

BMI: Body mass index; FPG: Fasting plasma glucose; GLP-1: Glucagon-like-polypeptide-1 receptor agonist; HbA1c: Hemoglobin A1c; SD: Standard deviation; SGLT-2i: Sodium/glucose cotransporter-2 inhibitors.

Table 3 Difference in antihyperglycemic therapy between three therapy groups

	Therapy group
	SGLT-2i, n (%)	GLP-1RA, n (%)	Simultaneous, n (%)
Insulin	11 (32.4)	28 (45.2)	11 (26.2)
Metformin	32 (94.1)	53 (85.5)	33 (78.6)
SU	4 (11.8)	12 (19.4)	6 (14.3)
Other OAD	3 (8.8)	10 (16.1)	8 (19.0)

GLP-1: Glucagon-like-poylpeptide-1 receptor agonist; OAD: Oral antihyperglycemic drugs; SGLT-2i: Sodium/glucose cotransporter-2 inhibitors; SU: Sulphonylurea.

Table 4 Change of parameters over a follow-up period in three time points according to therapy group

Parameter	Therapy	Baseline		6 mo		1 yr		Two-way repeated measures ANCOVA	F value	P value
		Mean	SD	Mean	SD	Mean	SD
HbA1c	SGLT-2i	7.74	0.78	7.03	0.72	7.09	0.83	Measurement point effect	7.035	0.002
	GLP-1RA	8.03	1.10	7.22	1.00	7.16	0.85	Therapy and measurement point	4.389	0.004
	Simultaneous	8.49	1.34	7.11	0.96	6.96	0.85	Therapy effect	0.432	0.650
FPG	SGLT-2i	7.98	1.40	7.11	2.41	6.84	1.26	Measurement point effect	2.647	0.091
	GLP-1RA	9.90	2.33	7.48	1.67	7.99	1.68	Therapy and measurement point	4.333	0.007
	simultaneous	10.86	3.53	7.53	1.64	7.33	1.31	Therapy effect	4.227	0.020
BMI	SGLT-2i	37.54	3.18	35.92	3.01	35.32	3.05	Measurement point effect	4.867	0.013
	GLP-1RA	38.76	4.60	37.27	4.44	36.80	4.43	Therapy and measurement point	2.123	0.092
	Simultaneous	39.66	5.59	37.22	5.41	36.94	5.42	Therapy effect	1.473	0.234

ANCOVA: Analysis of covariance; BMI: Body mass index; FPG: Fasting plasma glucose; HbA1c: Hemoglobin A1c; SGLT-2i: Sodium/glucose cotransporter-2 inhibitors; GLP-1RA: Glucagon-like-polypeptide-1 receptor agonist; SD: Standard deviation.

Table 5 Percentage of patients achieving target values according to therapy group

	SGLT-2i	GLP-1RA	Simultaneous	Chi-square	P value
HbA1c
< 7%	51.7	47.9	47.4	0.156	0.925
> 7%	48.3	52.1	52.6
Total	100.0	100.0	100.0
FPG
< 7 mmol	70.6	30.0	54.5	7.748	0.021
> 7 mmol	29.4	70.0	45.5
Total	100.0	100.0	100.0
PPG
< 10 mmol	90.0	84.4	72.7	2.775	0.250
> 10 mmol	10.0	15.6	27.3
Total	100.0	100.0	100.0
eGFR
> 60 mL/min per 1.73 m2	90.9	80.8	86.0	1.008	0.604
< 60 mL/min per 1.73 m2	9.1	19.2	14.0
Total	100.0	100.0	100.0
LDL
< 1.8 mmol	16.7	21.6	29.5	1.571	0.456
> 1.8 mmol	83.3	78.4	70.5
Total	100.0	100.0	100.0
LDL
< 2.5 mmol	66.7	54.1	52.3	1.413	0.493
> 2.5 mmol	33.3	45.9	47.7
Total	100.0	100.0
Weight loss > 5%
No	58.6	52.3	33.3	6.232	0.044
Yes	41.4	47.7	66.7
Total	100.0	100.0	100.0

BMI: Body mass index; eGFR: Estimated glomerular filtration rate; FPG: Fasting plasma glucose; GLP-1RA: Glucagon-like-polypeptide-1 receptor agonist; HbA1c: Hemoglobin A1c; LDL: Low-density lipoprotein cholesterol; PPG: Prandial plasma glucose; SGLT-2i: Sodium/glucose cotransporter-2 inhibitors.

Table 6 Percentage of patients achieving composite outcome

		n	(%)
HbA1c < 7% and 5% weight loss	No	88	(67.7)
	Yes	42	(32.3)
Total		130	(100.0)
HbA1c < 7%, 5% weight loss and LDL < 2.5 mmol/L	No	72	(81.8)
	Yes	16	(18.2)
Total		88	(100.0)

HbA1c: Hemoglobin A1c; LDL: Low-density lipoprotein cholesterol