J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Original Article

Volume 18, Number 5, May 2026, pages 313-325

Sodium-Glucose Co-Transporter 2 Inhibitor Use and Risk of Major Adverse Cardiovascular Events in Patients With Rheumatoid Arthritis and Type 2 Diabetes: A Retrospective Observational Cohort Study Using Real-World Data

↓ **Table 1.** MACE Composite Endpoint Components
MACE component	ICD-10-CM code/definition
ICD-10-CM: International Classification of Diseases, Tenth Revision, Clinical Modification; MACE: major adverse cardiovascular event.
Acute myocardial infarction	I21 (all subcategories)
Cerebral infarction (ischemic stroke)	I63 (all subcategories)
Heart failure	I50 (all subcategories)
Cardiac arrest	I46 (all subcategories)
Cardiovascular death	Deceased status in demographics

↓ Table 1. MACE Composite Endpoint Components

MACE component

ICD-10-CM code/definition

ICD-10-CM: International Classification of Diseases, Tenth Revision, Clinical Modification; MACE: major adverse cardiovascular event.

Acute myocardial infarction

I21 (all subcategories)

Cerebral infarction (ischemic stroke)

I63 (all subcategories)

Heart failure

I50 (all subcategories)

Cardiac arrest

I46 (all subcategories)

Cardiovascular death

Deceased status in demographics

↓ **Table 2.** Baseline Characteristics Before Propensity Score Matching (Unmatched Cohorts)
Characteristic	SGLT2 (n = 823)	DPP-4 (n = 284)	P-value	Std Diff
DPP-4: dipeptidyl peptidase-4; IQR: interquartile range; n: number of patients; %: percentage; SD: standard deviation; SGLT2: sodium-glucose co-transporter 2 inhibitors; Std Diff: standardized mean difference.
Demographics
Age (years), mean ± SD	64.1 ± 11.7	64.5 ± 12.0	0.633	0.033
Age (years), median (IQR)	65	65	-	-
Female sex, n (%)	610 (74.1)	211 (74.3)	0.953	0.004
Male sex, n (%)	213 (25.9)	73 (25.7)	0.953	0.004
White race, n (%)	561 (68.2)	177 (62.3)	0.072	0.123
Baseline comorbidities
Circulatory system diseases, n (%)	770 (93.6)	238 (83.8)	< 0.001	0.312
Hypertensive diseases, n (%)	736 (89.4)	229 (80.6)	< 0.001	0.248
Cerebrovascular diseases, n (%)	201 (24.4)	50 (17.6)	0.018	0.168
Pulmonary heart disease, n (%)	197 (23.9)	35 (12.3)	< 0.001	0.305
Chronic rheumatic heart disease, n (%)	145 (17.6)	18 (6.3)	< 0.001	0.353

↓ Table 2. Baseline Characteristics Before Propensity Score Matching (Unmatched Cohorts)

Characteristic

SGLT2 (n = 823)

DPP-4 (n = 284)

P-value

Std Diff

DPP-4: dipeptidyl peptidase-4; IQR: interquartile range; n: number of patients; %: percentage; SD: standard deviation; SGLT2: sodium-glucose co-transporter 2 inhibitors; Std Diff: standardized mean difference.

Demographics

Age (years), mean ± SD

64.1 ± 11.7

64.5 ± 12.0

0.633

0.033

Age (years), median (IQR)

Female sex, n (%)

610 (74.1)

211 (74.3)

0.953

0.004

Male sex, n (%)

213 (25.9)

73 (25.7)

0.953

0.004

White race, n (%)

561 (68.2)

177 (62.3)

0.072

0.123

Baseline comorbidities

Circulatory system diseases, n (%)

770 (93.6)

238 (83.8)

< 0.001

0.312

Hypertensive diseases, n (%)

736 (89.4)

229 (80.6)

< 0.001

0.248

Cerebrovascular diseases, n (%)

201 (24.4)

50 (17.6)

0.018

0.168

Pulmonary heart disease, n (%)

197 (23.9)

35 (12.3)

< 0.001

0.305

Chronic rheumatic heart disease, n (%)

145 (17.6)

18 (6.3)

< 0.001

0.353

↓ **Table 3.** Baseline Characteristics After Propensity Score Matching (Matched Cohorts, n = 277 per Group)
Characteristic	SGLT2 (n = 277)	DPP-4 (n = 277)	P-value	Std Diff
DPP-4: dipeptidyl peptidase-4; IQR: interquartile range; SD: standard deviation; SGLT2: sodium-glucose co-transporter 2; Std Diff: standardized difference.
Demographics
Age (years), mean ± SD	63.6 ± 11.0	64.4 ± 12.0	0.377	0.075
Age (years), median (IQR)	64	65	-	-
Female sex, n (%)	210 (75.8)	206 (74.4)	0.694	0.033
Male sex, n (%)	67 (24.2)	71 (25.6)	0.694	0.033
White race, n (%)	187 (67.5)	174 (62.8)	0.246	0.099
Baseline comorbidities
Circulatory system diseases, n (%)	235 (84.8)	238 (85.9)	0.718	0.031
Hypertensive diseases, n (%)	225 (81.2)	229 (82.7)	0.659	0.038
Cerebrovascular diseases, n (%)	34 (12.3)	50 (18.1)	0.058	0.162
Pulmonary heart disease, n (%)	34 (12.3)	35 (12.6)	0.898	0.011
Chronic rheumatic heart disease, n (%)	17 (6.1)	18 (6.5)	0.861	0.015

↓ Table 3. Baseline Characteristics After Propensity Score Matching (Matched Cohorts, n = 277 per Group)

Characteristic

SGLT2 (n = 277)

DPP-4 (n = 277)

P-value

Std Diff

DPP-4: dipeptidyl peptidase-4; IQR: interquartile range; SD: standard deviation; SGLT2: sodium-glucose co-transporter 2; Std Diff: standardized difference.

Demographics

Age (years), mean ± SD

63.6 ± 11.0

64.4 ± 12.0

0.377

0.075

Age (years), median (IQR)

Female sex, n (%)

210 (75.8)

206 (74.4)

0.694

0.033

Male sex, n (%)

67 (24.2)

71 (25.6)

0.694

0.033

White race, n (%)

187 (67.5)

174 (62.8)

0.246

0.099

Baseline comorbidities

Circulatory system diseases, n (%)

235 (84.8)

238 (85.9)

0.718

0.031

Hypertensive diseases, n (%)

225 (81.2)

229 (82.7)

0.659

0.038

Cerebrovascular diseases, n (%)

34 (12.3)

50 (18.1)

0.058

0.162

Pulmonary heart disease, n (%)

34 (12.3)

35 (12.6)

0.898

0.011

Chronic rheumatic heart disease, n (%)

17 (6.1)

18 (6.5)

0.861

0.015

↓ **Table 4.** Follow-Up Duration Before and After Propensity Score Matching
Cohort	Mean (days)	SD (days)	Median (days)	IQR (days)
DPP-4: dipeptidyl peptidase-4; IQR: interquartile range; n: number of patients; SD: standard deviation; SGLT2: sodium-glucose co-transporter 2.
Before propensity score matching
SGLT2 inhibitors (n = 823)	1,275.97	979.45	1,009	1,300
DPP-4 inhibitors (n = 284)	2,361.68	1,430.90	2,325	2,022
After propensity score matching
SGLT2 inhibitors (n = 277)	1,432.98	1,032.95	1,140	1,489
DPP-4 inhibitors (n = 277)	2,347.93	1,421.38	2,324	2,011

↓ Table 4. Follow-Up Duration Before and After Propensity Score Matching

Cohort

Mean (days)

SD (days)

Median (days)

IQR (days)

DPP-4: dipeptidyl peptidase-4; IQR: interquartile range; n: number of patients; SD: standard deviation; SGLT2: sodium-glucose co-transporter 2.

Before propensity score matching

SGLT2 inhibitors (n = 823)

1,275.97

979.45

1,009

1,300

DPP-4 inhibitors (n = 284)

2,361.68

1,430.90

2,325

2,022

After propensity score matching

SGLT2 inhibitors (n = 277)

1,432.98

1,032.95

1,140

1,489

DPP-4 inhibitors (n = 277)

2,347.93

1,421.38

2,324

2,011

↓ **Table 5.** Risk Analysis for Composite MACE Endpoint (Propensity-Matched Cohorts)
Measure	SGLT2 (n = 277)	DPP-4 (n = 277)	Estimate (95% CI)	P-value
CI: confidence interval; DPP-4: dipeptidyl peptidase-4; MACE: major adverse cardiovascular event; n: number of patients; SGLT2: sodium-glucose co-transporter 2.
Patients with MACE, n	119	135	-	-
Risk (proportion)	0.430 (43.0%)	0.487 (48.7%)	-	-
Risk difference	-	-	-0.058 (−0.141 to 0.025)	0.172
Risk ratio	-	-	0.881 (0.735–1.057)	-
Odds ratio	-	-	0.792 (0.567–1.107)	-

↓ Table 5. Risk Analysis for Composite MACE Endpoint (Propensity-Matched Cohorts)

Measure

SGLT2 (n = 277)

DPP-4 (n = 277)

Estimate (95% CI)

P-value

CI: confidence interval; DPP-4: dipeptidyl peptidase-4; MACE: major adverse cardiovascular event; n: number of patients; SGLT2: sodium-glucose co-transporter 2.

Patients with MACE, n

119

135

Risk (proportion)

0.430 (43.0%)

0.487 (48.7%)

Risk difference

-0.058 (−0.141 to 0.025)

0.172

Risk ratio

0.881 (0.735–1.057)

Odds ratio

0.792 (0.567–1.107)

↓ **Table 6.** Kaplan–Meier Survival Analysis for Time to First MACE
Parameter	SGLT2 inhibitors (n = 277)	DPP-4 inhibitors (n = 277)
DPP-4: dipeptidyl peptidase-4; MACE: major adverse cardiovascular event; n: number of patients; SGLT2: sodium-glucose co-transporter 2.
Patients with MACE, n	119	135
Median survival (days)	2227	2750
Median survival (years)	6.1	7.5
Survival probability at end of follow-up	38.45%	9.50%

↓ Table 6. Kaplan–Meier Survival Analysis for Time to First MACE

Parameter

SGLT2 inhibitors (n = 277)

DPP-4 inhibitors (n = 277)

DPP-4: dipeptidyl peptidase-4; MACE: major adverse cardiovascular event; n: number of patients; SGLT2: sodium-glucose co-transporter 2.

Patients with MACE, n

119

135

Median survival (days)

2227

2750

Median survival (years)

6.1

7.5

Survival probability at end of follow-up

38.45%

9.50%

↓ **Table 7.** Cox Proportional Hazards Regression and Proportionality Test
Parameter	Estimate	95% CI	P-value
CI: confidence interval; χ²: Chi-square statistic; DPP-4: dipeptidyl peptidase-4; df: degrees of freedom; SGLT2: sodium-glucose co-transporter 2.
Hazard ratio (SGLT2 vs. DPP-4)	1.284	0.998–1.652	-
Test for proportionality (χ², df = 1)	4.981	-	0.026

↓ Table 7. Cox Proportional Hazards Regression and Proportionality Test

Parameter

Estimate

95% CI

P-value

CI: confidence interval; χ²: Chi-square statistic; DPP-4: dipeptidyl peptidase-4; df: degrees of freedom; SGLT2: sodium-glucose co-transporter 2.

Hazard ratio (SGLT2 vs. DPP-4)

1.284

0.998–1.652

Test for proportionality (χ², df = 1)

4.981

0.026