Diabetes Metab J.  2024 Mar;48(2):242-252. 10.4093/dmj.2023.0201.

Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis

• Chuang MH
• Tang YS
• Chen JY
• Pan HC
• Liao HW
• Chu WK
• Cheng CY
• Wu VC
• Heung M

• KMID: 2553595
• DOI: http://doi.org/10.4093/dmj.2023.0201

Abstract

Background
The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined.
Methods
We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis.
Results
We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group.
Conclusion
Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Keyword

Diabetes mellitus, type 2; Glomerular filtration rate; Kidney; Sodium-glucose transporter 2 inhibitors

Figure

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  Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of study selection for the current systematic review.

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  Fig. 2. Forest plot showing difference in slope of annual estimated glomerular filtration rate (eGFR) decline between the dipping and non-dipping groups. SD, standard deviation; IV, inverse variance; CI, confidence interval.

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  Fig. 3. Forest plot illustrating the comparison of major kidney adverse events between the dipping and non-dipping groups. HR, hazard ratio; SE, standard error; IV, inverse variance; CI, confidence interval; eGFR, estimated glomerular filtration rate.

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  Fig. 4. Comparisons of cardiovascular (CV) outcomes, all-cause death and adverse events (AEs) between the dipping and non-dipping groups. HR, hazard ratio; CI, confidence interval; HHF, hospitalized heart failure; OR, odds ratio; SGLT2i, sodium-glucose cotransporter-2 inhibitor.

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