Kawai Y, Uneda K, Yamada T, et al. Comparison of effects of SGLT-2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in type 2 diabetes mellitus patients with/without albuminuria: a systematic review and network meta-analysis. Diabetes Res Clin Pract. 2021 Nov 12:109146. doi: 10.1016/j.diabres.2021.109146. (Systematic review)

AIMS: It remains unclear which sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are most effective for preventing cardiovascular and renal events in type 2 diabetes mellitus (T2DM) patients, depending on the presence of albuminuria. We conducted a network meta-analysis to compare the efficacy of these two drug classes in T2DM patients with/without albuminuria.

METHODS: We searched the Medline, EMBASE, Cochrane Library databases, and gray literature up to April 20, 2021. We included randomized controlled trials that reported the risk of major adverse cardiovascular events (MACE) and composite of renal outcomes in T2DM.

RESULTS: A total of nine studies (81,206 patients) were included. In patients with/without albuminuria, SGLT-2 inhibitors did not significantly reduce the risk of MACE compared with GLP-1 RAs (risk ratio [RR] [95% confidence interval]; 0.96 [0.82-1.12] and 0.94 [0.81-1.10], respectively). In contrast, compared with GLP-1 RAs, SGLT-2 inhibitors were associated with significantly lower renal risk in both patients with/without albuminuria (RR [95% CI]; 0.75 [0.63-0.89] and 0.59 [0.44-0.79], respectively).

CONCLUSIONS: SGLT-2 inhibitors may be superior to GLP-1 RAs for renal outcomes in T2DM patients with/without albuminuria, although there was no difference in the risk of MACE.

Discipline Area Score
Endocrine 6 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Cardiology 6 / 7
Nephrology 5 / 7
Comments from MORE raters

Cardiology rater

Many previous trials of SGLT2i showed multiple effects of CHF, CKD and glucose metabolism. Which mechanism caused such physiological effects is still unknown. In addition, GLP1RA showed good effect on glucose metabolism, but the effect is unknown in CHF and CKD. This article showed superiority of SGLT2i to GLP1RA, but it still needs to analyze its functional mechanism.

Endocrine rater

This network meta analysis confirms the renal protection afforded by the SGLT2 inhibitors vs that of GLP-1 analogues. This brings us to the many advantages of using SGLT2 inhibitors in patients with diabetes. Although mechanisms for such advantages were alluded to, this requires further investigation and we wait for these results.

Endocrine rater

This is a definitive metanalysis, looking at the studies of SGLT2 inhibitors and GLP-1 receptor agonists on cardiac and renal disease. They looked at all the major studies, including CANVAS, CREDENCE, EMPA-REG, DECLARE-TIMI, VERTIS, LEADER, ELIXA and REWIND. They showed similar effectiveness at decreasing MACE in both classes, and a slight advantage for SGLT2 inhibitors for renal outcomes. It's good to have all of these studies compared in one place.

General Internal Medicine-Primary Care(US) rater

This is a really important and helpful review with a good list of references to explore further.

Nephrology rater

As a nephrologist, I think that this is interesting information. However, it added little to the current evidence.
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