SGLT2i and GLP-1RA in Cardiometabolic and Renal Diseases: From Glycemic Control to Adipose Tissue Inflammation and Senescence

Table 1

Summary of clinical evidence regarding SGLT2i in cardiovascular, renal, and anthropometric outcomes.

Author (REF)	Methodology	Population		Outcomes
Toyama et al. [28]	Meta-analysis (27 randomized controlled trials).	Efficacy and safety in patients with T2DM and CKD.	7.363	(1) Reduced the risk of cardiovascular death, nonfatal myocardial infarction or stroke (RR, 0.81; 95% CI, 0.70-0.94), and heart failure (RR, 0.61; 95% CI; 0.48-0.78).; (2) Reduced the risk of the composite renal outcomes (HR, 0.71; 95% CI, 0.53-0.95).; (3) These agents diminished the annual decline in eGFR slope (placebo-subtracted difference of 1.35 mL/1.73 m^2/y; 95% CI, 0.78-1.93) and control HbA1c (-0.29; 95% CI, -0.39 to -0.19), blood pressure, body weight, and albuminuria.
Neuen et al. [29]	Meta-analysis (4 randomized, controlled clinical trials).	Effects on major kidney outcomes in patients with T2DM.	38.723	Lowered the risk of dialysis, transplantation, or death due to kidney disease (RR, 0.67; 95% CI, 0.52–0.86; ), end-stage kidney disease (0.65; 0.53–0.81; ), and acute kidney injury (0.75; 0.66–0.85; ).
Bae et al. [27]	Meta-analysis (48 randomized controlled clinical trials).	Effects on individual renal outcomes in patients with T2DM.	58.165	(1) Diminished worsening of nephropathy (RR, 0.73; 95% CI, 0.58 to 0.93; ); significantly reduced urine albumin-to-creatinine ratio (WMD, −14.64 mg/g; 95% CI, −25.15 to −4.12; ).; (2) These drugs lowered the risk of microalbuminuria (RR, 0.69; 95% CI, 0.49 to 0.97; ) and macroalbuminuria (RR, 0.49; 95% CI, 0.33 to 0.73; ).
Heerspink et al. [23]	Randomized, double-blind, placebo-controlled study.	Effects of dapagliflozin on eGFR and death from renal or CV causes in CKD patients, with or without T2DM.	4304	(1) In CKD patients, regardless of the presence or absence of DM, the risk of a composite of a sustained preservation in the eGFR of at least 50%.; (2) Progression to end-stage kidney disease or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo.
McMurray et al. [24]	Randomized, placebo-controlled trial.	Effects of dapagliflozin or placebo in addition to recommended therapy on patients with HF (ejection fraction of <40%).	4744	(1) The primary outcome occurred 16.3% in the dapagliflozin group and 21.2% in the placebo group (hazard ratio, 0.74; 95% confidence interval (CI), 0.65 to 0.85; ).; (2) Findings in patients with or without diabetes were similar.
Packer et al. [25]	Randomized, placebo-controlled study.	Effects of empagliflozin or placebo in addition to usual therapy on patients with HF (ejection ).	3730	Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for HF in patients with preserved ejection fraction, regardless of the presence or absence of diabetes.
Bolinder et al. [47]	Randomized, double-blind, placebo-controlled study.	Effects of dapagliflozin on glycemic control and body composition in T2DM.	140	Dapagliflozin lowered HbA1c by -0.3%, weight by -4.54 kg, waist circumference by -5.0 cm, and fat mass by -2.80 kg.
Bouchi et al. [49]	Randomized, controlled, 24-week study.	Effects of intensive exercise and dapagliflozin on body composition in T2DM.	146	(1) Intensive exercise did not significantly reduce fat-free mass after treatment (LSM difference -0.1 kg; 95% CI, -0.5 to 0.4).; (2) Dapagliflozin was able to promote the reduction in abdominal fat, seemingly leading to further improvements of hyperglycemia and chronic inflammation.
Bolinder et al. [50]	Randomized, multicenter, double-blind, placebo-controlled 24-week study.	Effects of dapagliflozin on body composition measurements on diabetic patients.	182	(1) Dapagliflozin decreased total body weight (95% CI, -2.84 to -1.31; ), waist circumference (95% CI, -2.74 to -0.31; ), total body fat mass (95% CI, -2.22 to -0.74; ), visceral adipose tissue (95% CI, -448.1 to -68.6; ), and subcutaneous adipose tissue (95% CI, -359.7 to -10.1; ).