Table 2 Summary of evidence for treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies for cardiovascular outcomes (including heart failure).

Race/ethnicity

0

0

3^76,83,90

0

2^160,161

4^76,78,83,110

No heterogeneity by race/ethnicity for SGLT2is; Potential increased cardiovascular benefit in Asians associated with GLP1-RA use, but results are inconsistent.

History of CVD

3^105,106,107

8^{125,162,163,164,165,166,167}

7^{83,90,91,92,93,94,95,98,99}

4^{104,105,106,109}

3^86,168,169

5^{2,80,83,95,112}

No consistent impact on SGLT2i or GLP1-RA outcomes.

Age

2^107,108

3^121,165,170

3^83,92,94

2^104,109

1¹⁷¹

4^78,79,80,83

No consistent heterogeneity by age for SGLT2is; No evidence of age effect for GLP1-RAs.

Sex

3^102,107,108

1¹⁶⁵

5^{83,90,92,94,96,99}

4^{102,104,109,110}

3^171,172,173

4^{79,83,174,175}

No consistent heterogeneity by sex for SGLT2is or GLP1-RAs.

Renal function

1¹⁰⁸

2^127,176

5^{83,84,90,92,94}

2^104,109

6^{16,117,118,119,171,177}

5^{2,82,83,84,95}

No consistent heterogeneity by renal function on cardiovascular outcomes for SGLT2is; No evidence of heterogeneity by renal function on cardiovascular outcomes for GLP1-RAs.

BMI

0

1¹²⁶

5^{83,90,92,94,97}

1¹¹⁰

2^87,171

3^79,83,97

No consistent heterogeneity by BMI for SGLT2is; Some inconsistent evidence suggests that higher baseline BMI may improve cardiovascular efficacy of GLP1-RAs.

Genetics

0

0

0

0

0

0

Non-routine biomarkers

0

0

0

0

5^{89,178,179,180,181}

0

The greater benefit of SGLT2i in those with high levels of 3 biomarkers: hs Cardiac Troponin T, soluble suppression of tumorigenesis-2 (sST2), and insulin-like growth factor binding protein 7 (IGFBP7) levels

Heart Failure (HF)

Ethnicity

0

1¹⁸²

1⁷⁶

0

4^{160,161,183,184}

4^76,77,78,79

Possibly greater relative benefit of SGLT2i in Asian and Black compared to white ethnicity; Potential increased efficacy of GLP1-RAs in Asian ethnicity.

Age

0

2^165,170

1⁹⁴

1¹⁰⁴

1¹⁸³

3^79,81

No heterogeneity by age for SGLT2is or GLP1-RAs.

Sex

0

2¹⁸²

1⁹⁴

2^102,104

3^172,173,183

3^79,81,175

No heterogeneity by sex for SGLT2is or GLP1-RAs.

BMI

0

0

1⁹⁴

0

3^87,183,184

2^79,81

No consistent heterogeneity by BMI for SGLT2is or GLP1-RAs.

History of CVD

2^105,106

3^165,166,182

3^93,94,95

4^{101,104,105,106}

4^{86,168,169,185}

4^2,77,81,85

No consistent heterogeneity by CVD history for SGLT2is or GLP1-RAs.

History of HF

0

0

0

1¹⁰⁶

1⁸⁸

4^2,77,81,85

No consistent heterogeneity by HF history for SGLT2is; No analysis on heterogeneity by HF history was performed for GLP1-RAs.

HF severity/score

0

0

0

1¹⁰³

3^163,186,187

1⁷⁷

Greater relative benefit of SGLT2i in those with NYHA class II vs class III/IV in one meta-analysis; No analysis of heterogeneity by HF severity/score performed for GLP1-RAs.

Renal function

0

0

1⁹⁴

2^103,104

6^{16,117,118,119,177,183}

5^{2,77,81,82,85}

No consistent heterogeneity in renal function. A single meta-analysis showed greater SGLT-2 benefit with lower eGFR and higher ACR; No evidence for heterogeneity by renal function for GLP1-RAs.

Genetics

0

0

0

0

0

0

Non-routine biomarkers

0

0

0

0

6^{89,159,178,179,180,188}

0

No heterogeneity across a variety of non-routine biomarkers. No analysis of heterogeneity by non-routine biomarkers was performed for GLP1-RAs.