Renal and metabolic effects of semaglutide plus canagliflozin vs canagliflozin alone in type 2 diabetic nephropathy

Table 1 General characteristics, n (%)

Parameter	CM group (n = 107)	CSCT group (n = 104)	t/χ²	P value
Age (years)	63.12 ± 6.14	62.86 ± 6.26	0.305	0.761
Gender			0.004	0.949
Male	55 (51.40)	53 (50.96)
Female	52 (48.60)	51 (49.04)
BMI (kg/m2)	28.43 ± 3.46	28.51 ± 3.52	0.163	0.870
Weight (kg)	79.63 ± 14.11	80.12 ± 14.23	0.251	0.802
Educational level			0.024	0.988
Primary	18 (16.82)	17 (16.35)
Secondary	54 (50.47)	52 (50.00)
Tertiary	35 (32.71)	35 (33.65)
Current smoking	23 (21.50)	21 (20.19)	0.054	0.816
Pulse rate (beats per min)	74.13 ± 5.11	74.22 ± 5.21	0.128	0.899
Duration of diabetes mellitus (years)	10.52 ± 4.10	11.12 ± 3.97	1.068	0.287
Systolic blood pressure (mmHg)	138.21 ± 4.12	138.37 ± 4.06	0.274	0.784
Diastolic blood pressure (mmHg)	78.34 ± 3.26	77.89 ± 3.45	0.983	0.327
LVEF			0.213	0.899
< 40%	18 (16.82)	20 (19.23)
40% to < 50%	26 (24.30)	25 (24.04)
≥ 50%	63 (58.88)	59 (56.73)
Diabetic nephropathy staging			0.011	0.916
G3a	85 (79.44)	82 (78.85)
G3b	22 (20.56)	22 (21.15)

BMI: Body mass index; LVEF: Left ventricular ejection fraction; CM: Canagliflozin monotherapy; CSCT: Canagliflozin and semaglutide combination therapy.

Table 2 Comparison of renal function between two groups of patients before and after treatment

Parameter	Time	CM group (n = 107)	CSCT group (n = 104)	t	P value
Serum creatinine (mg/dL)	Baseline	1.04 ± 0.32	1.04 ± 0.29	0.122	0.903
	6 months	1.05 ± 0.35	1.06 ± 0.31	0.265	0.791
GFR (mL/minute/1.73 m2)	Baseline	50.83 ± 5.01	50.92 ± 5.19	0.126	0.900
	6 months	50.13 ± 4.61	50.52 ± 4.87	0.603	0.547
ACR (mg/g)	Baseline	211.51 ± 30.11	207.54 ± 30.15	0.956	0.340
	6 months	158.11 ± 28.85	145.87 ± 29.23	3.062	0.002

GFR: Glomerular filtration rate; ACR: Albumin/creatinine ratio; CM: Canagliflozin monotherapy; CSCT: Canagliflozin and semaglutide combination therapy.

Table 3 Comparison of blood lipid levels between two groups of patients before and after treatment

Parameter	Time	CM group (n = 107)	CSCT group (n = 104)	t	P value
Tot-cholesterol (mg/dL)	Baseline	177.23 ± 34.56	180.25 ± 32.56	0.653	0.515
	6 months	171.45 ± 32.69	162.41 ± 31.79	2.037	0.043
HDL (mg/dL)	Baseline	45.26 ± 9.56	45.15 ± 9.89	0.079	0.937
	6 months	45.34 ± 8.66	47.69 ± 8.28	2.017	0.045
LDL (mg/dL)	Baseline	101.49 ± 35.26	105.21 ± 35.46	0.764	0.446
	6 months	94.86 ± 27.64	86.74 ± 27.12	2.154	0.032
Triglycerides (mg/dL)	Baseline	145.32 ± 35.64	142.89 ± 35.39	0.496	0.621
	6 months	135.21 ± 28.22	127.56 ± 25.26	2.072	0.040

HDL: High density lipoprotein; LDL: Low density lipoprotein; CM: Canagliflozin monotherapy; CSCT: Canagliflozin and semaglutide combination therapy.

Table 4 Comparison of islet function and serum asprosin and free fatty acids levels between two groups of patients before and after treatment

Parameter	Time	CM group (n = 107)	CSCT group (n = 104)	t	P value
FFA (mmol/L)	Baseline	0.55 ± 0.17	0.56 ± 0.18	0.334	0.739
	6 months	0.52 ± 0.16	0.46 ± 0.12	3.172	0.002
HOMA-IR	Baseline	5.19 ± 0.45	5.22 ± 0.42	0.379	0.705
	6 months	4.08 ± 0.36	3.94 ± 0.45	2.582	0.011
HOMA-β	Baseline	45.99 ± 5.64	45.98 ± 5.56	0.007	0.994
	6 months	49.36 ± 5.87	51.22 ± 5.79	2.310	0.022
Asprosin (ng/mL)	Baseline	7.52 ± 1.19	7.57 ± 1.21	0.298	0.766
	6 months	6.33 ± 0.52	6.16 ± 0.48	2.528	0.012

FFA: Free fatty acid; HOMA-IR: Insulin resistance index; HOMA-β: Islet β-cell function; CM: Canagliflozin monotherapy; CSCT: Canagliflozin and semaglutide combination therapy.

Table 5 Comparison of oxidative stress and inflammatory factor levels between two groups of patients before and after treatment

Parameter	Time	CM group (n = 107)	CSCT group (n = 104)	t	P value
MDA (μmol/L)	Baseline	4.65 ± 1.09	4.68 ± 1.11	0.158	0.875
	6 months	4.12 ± 0.99	3.78 ± 1.13	2.336	0.020
SOD (U/mg prot)	Baseline	42.05 ± 5.27	42.69 ± 5.35	0.882	0.379
	6 months	45.49 ± 5.55	47.46 ± 5.46	2.597	0.010
TNF-α (ng/L)	Baseline	15.19 ± 3.12	15.26 ± 3.26	0.162	0.871
	6 months	10.43 ± 2.36	9.68 ± 2.29	2.325	0.021
CRP (mg/L)	Baseline	2.45 ± 0.42	2.47 ± 0.45	0.334	0.739
	6 months	1.74 ± 0.26	1.39 ± 0.24	10.144	< 0.001

MDA: Malondialdehyde; SOD: Superoxide dismutase; TNF-α: Tumor necrosis factor-α; CRP: C-reactive protein; CM: Canagliflozin monotherapy; CSCT: Canagliflozin and semaglutide combination therapy.

Table 6 Adverse events occurring in two groups of patients during the treatment process, n (%)

Parameter	CM group (n = 107)	CSCT group (n = 104)	χ²	P value
GI adverse events	11 (10.28)	15 (14.42)	0.838	0.360
Urinary tract infections	5 (4.67)	7 (6.73)	0.416	0.519
Hypoglycaemia	10 (9.35)	8 (7.69)	0.185	0.667
Nervous system disorders	3 (2.80)	5 (4.81)	0.161	0.688
Diabetic retinopathy	2 (1.87)	1 (0.96)	0.001	0.980

GI: Gastrointestinal; CM: Canagliflozin monotherapy; CSCT: Canagliflozin and semaglutide combination therapy.