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

Table 2

Summary of clinical evidence regarding GLP-1RA in cardiovascular, renal, and anthropometric outcomes.

Author (REF)	Methodology	Population		Outcomes
Giugliano et al. [93]	Meta-analysis (7 large-scale CV outcome trials).	Impact of GLP-1RA on cardiorenal variables in patients with T2DM.	56.004	(1) Decreased major CV events by 13% (HR, 0.87; 95% CI, 0.80-0.96; ) and the risk of CV death by 12% (HR, 0.91 (0.86–0.97)), of nonfatal stroke by 16%, of hospitalization for heart failure by 9%, of all-cause mortality by 11% (HR, 0.89 (0.79–0.99)).; (2) Reduced the broad composite kidney outcome by 17% (HR, 0.83 (0.69–1.00)), which was driven by a 24% reduction in macroalbuminuria (HR, 0.76 (0.68–0.86)).
Palmer et al. [95]	Meta-analysis (764 randomized, controlled clinical trials).	Evaluate treatment with SGLT-2i and GLP-1RA in patients with T2DM at varying cardiorenal risks.	421.346	(1) SGLT2i and GLP-1RA reduced all-cause mortality, CV mortality, nonfatal myocardial infarction, and kidney failure.; (2) GLP-1RA reduced nonfatal stroke more than SGLT-2i, and SGLT-2i reduced mortality and admission to hospital for heart failure more than GLP-1RA.
Zelniker et al. [94]	Meta-analysis (8 clinical trials).	Benefits of SGLT2i/GLP-1RA in patients with or without atherosclerotic CV disease.	77.242	(1) SGLT2i and GLP-1RA lowered major adverse CV events by 11% (HR, 0.89; 95% CI, 0.83-0.96; ) and 12% (HR, 0.88; 95% CI, 0.84-0.94; ).; (2) The effect was limited to a 14% reduction in those with established atherosclerotic CV disease (HR, 0.86; 95% CI, 0.80-0.93; ).; (3) SGLT2i (HR, 0.62; 95% CI, 0.58-0.67; ) and GLP1-RAs (HR, 0.82; 95% CI, 0.75-0.89; ) decreased the risk of CKD progression including macroalbuminuria. However, only SGLT2i diminished the risk of worsening eGFR, end-stage kidney disease, or renal death (HR, 0.55; 95% CI, 0.48-0.64; ).
Kristensen et al. [92]	(1) Meta-analysis (7 randomized placebo-controlled trials).	Effects of GLP-1RA on CV outcomes.	56.004	(1) The treatment diminished major adverse CV events by 12% (HR, 0.88; 95% CI, 0.82-0.94; ), all-cause mortality by 12% (0.88, 0.83-0.95; ), and hospital admission for heart failure by 9% (0.91, 0.83-0.99; ).; (2) Decrease the broad composite kidney outcome by 17% (0.83, 0.78-0.89; ).
Davies et al. [96]	Randomized, double-blind, placebo-controlled, parallel-group trial.	Efficacy and safety of liraglutide for weight management in diabetic patients.	846	Weight loss was 6.0% with subcutaneous liraglutide (3.0 mg dose) and 4.7% with liraglutide (1.8 mg dose) (estimated difference for liraglutide (3.0 mg) vs. placebo, -4.00% (95% CI, -5.10% to -2.90%); liraglutide (1.8 mg) vs. placebo, -2.71% (95% CI, -4.00% to -1.42%); ).
Bunck et al. [99]	Randomized, double-blinded, placebo-controlledstudy.	Effects of a 1-year treatment with exenatide or insulin glargine on diabetic patients.	69	Exenatide decreased prandial glucose, triglycerides, apo-B48, calculated VLDL-C, FFA, and MDA ().
Brock et al. [125]	Randomized, double-blinded, placebo-controlledtrial.	Evaluated anti-inflammatory properties of liraglutide in diabetic patients.	39	(1) The treatment was associated with weight loss (-3.38 kg; 95% CI, -5.29, -1.48; ) and a reduction in urine albumin/creatinine ratio (-40.2%; 95% CI, -60.6, -9.5; ).; (2) Significantly decreased interleukin-6 levels (-22.6%; 95% CI, -38.1, -3.2; ).