Table 4.

Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework summary of findings.

Drug class	Outcome	Overall certainty of evidence	Elaboration on evidence certainty	Evidence for specific biomarkers
SGLT2i	CVD	Moderate	Majority of evidence from post-hoc analysis of RCTs and RCT-based meta-analysis	- History of prior cardiovascular disease probably does not alter relative benefit (no effect, moderate certainty) - Ethnicity probably does alter relative benefit, with a greater relative heart failure benefit in people of black and Asian ethnicity compared to those of white ethnicity (moderate effect, moderate certainty) - Other biomarkers may not be associated with treatment effect heterogeneity (no effect, low certainty)
	Renal	Moderate	Majority of evidence from post-hoc analysis of RCTs and RCT-based meta-analysis	- Biomarkers may not be associated with treatment effect heterogeneity (no effect, low certainty)
	Glycaemia	Moderate	Majority of evidence from post-hoc analysis of RCTs and RCT-based meta-analysis	- Lower renal function results in lesser glycaemic response (moderate effect, high certainty) - Other biomarkers may not be associated with treatment effect heterogeneity (no effect, low certainty)
GLP1-RA	CVD	Moderate	Majority of evidence from post-hoc analysis of RCTs and RCT-based meta-analysis	- History of prior cardiovascular disease probably does not alter relative benefit (no effect, moderate certainty) - Ethnicity probably does alter relative benefit, with a greater relative CVD benefit in people of black and Asian ethnicity compared to those of white ethnicity (moderate effect, moderate certainty) - Other biomarkers may not be associated with treatment effect heterogeneity (no effect, low certainty)
	Renal	Moderate	Majority of evidence from post-hoc analysis of RCTs and RCT-based meta-analysis	- Biomarkers may not be associated with treatment effect heterogeneity (no effect, low certainty)
	Glycaemia	Low	Majority of evidence from observational studies	- Lower insulin secretion probably results in lesser glycaemic response (moderate effect, moderate certainty) - Other biomarkers may not be associated with treatment effect heterogeneity (no effect, low certainty)