Dataset Information

The Effect of Sodium-Glucose Cotransporter Inhibitors on Renal Function as Adjunctive to Insulin in Adults with Type 1 Diabetes: An Updated Multilevel Meta-analysis of Randomized Controlled Trials.

ABSTRACT:

Introduction

This systematic review aimed to summarize the existing evidence from published randomized controlled trials (RCTs) on the impact of sodium-glucose cotransporter (SGLT) inhibitors on albuminuria levels and renal function in patients with type 1 diabetes mellitus (T1D).

Methods

The literature search was performed through Medline (via PubMed), Cochrane Library, and Scopus until November 11, 2023. Double-independent study selection, data extraction, and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis.

Results

In total, 5221 participants with T1D among 11 RCTs were analyzed. All RCTs had low risk of bias according to the Cochrane Collaboration tool (RoB 2). SGLT inhibitors were associated with a significantly greater reduction in urine albumin-to-creatinine ratio (UACR) compared to controls (MD = - 23.13%; 95% CI = [- 33.69, - 12.57]; P < 0.001; level of evidence high). On the basis of subgroup analysis, this effect was consistent across all available SGLT inhibitors, irrespective of the dosage. Finally, a neutral class effect was observed on the estimated glomerular filtration rate (eGFR, MD = - 1.03 mL/min/1.73 m²; 95% CI = [- 2.26, 0.19]; P = 0.1; level of evidence moderate). Only empagliflozin was associated with a significant reduction in eGFR compared to placebo (MD = - 2.23 mL/min/1.73 m²; 95% CI = [- 3.62, - 0.84]; P = 0.002).

Conclusion

Our findings suggest that adjunctive therapy with SGLT inhibitors results in a significant reduction in albuminuria, while their use is associated with a neutral effect on creatinine clearance, as a measure of renal function. Future renal outcome trials are needed to assess SGLT inhibitors' role in the pharmacological armamentarium against diabetic nephropathy in T1D.

SUBMITTER: Karakasis P

PROVIDER: S-EPMC10838855 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

The Effect of Sodium-Glucose Cotransporter Inhibitors on Renal Function as Adjunctive to Insulin in Adults with Type 1 Diabetes: An Updated Multilevel Meta-analysis of Randomized Controlled Trials.

Karakasis Paschalis P Popovic Djordje S DS Patoulias Dimitrios D Koufakis Theocharis T Papanas Nikolaos N Fragakis Nikolaos N Rizzo Manfredi M

Diabetes therapy : research, treatment and education of diabetes and related disorders 20240105 2

<h4>Introduction</h4>This systematic review aimed to summarize the existing evidence from published randomized controlled trials (RCTs) on the impact of sodium-glucose cotransporter (SGLT) inhibitors on albuminuria levels and renal function in patients with type 1 diabetes mellitus (T1D).<h4>Methods</h4>The literature search was performed through Medline (via PubMed), Cochrane Library, and Scopus until November 11, 2023. Double-independent study selection, data extraction, and quality assessment ...[more]

PMID: 38180713

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Project description:Sodium-glucose co-transporter 2 inhibitors (SGLT2is) reduce albuminuria and hard renal outcomes (decline of renal function, renal replacement therapy and renal death) in patients with/without type 2 diabetes at high cardiovascular or renal risk. The question arises whether baseline albuminuria also influences renal outcomes with SGLT2is as reported with renin-angiotensin-aldosterone system inhibitors. Post hoc analyses focusing on albuminuria and renal outcomes of four cardiovascular outcome trials [EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), CANVAS (Canagliflozin Cardiovascular Assessment Study), DECLARE-TIMI 58 (Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) and VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial)] and some renal data from two heart failure trials [Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) and EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction)] showed renal protection with SGLT2is without significant interaction (P > 0.10) when comparing renal outcomes according to baseline levels (A1, A2 and A3) of urinary albumin:creatinine ratio (UACR), a finding confirmed in a dedicated meta-analysis. Two trials [CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy) and DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease)] specifically recruited patients with CKD and UACRs of 200-5000 mg/g. A post hoc analysis of CREDENCE that distinguished three subgroups according to UACR (300-1000, 1000-3000 and >3000 mg/g) showed a greater relative reduction in UACR in patients with lower baseline albuminuria levels (P for interaction = 0.03). Patients with a UACR >1000 mg/g showed a significantly greater reduction in absolute (P for interaction < 0.001) and a trend in relative (P for interaction = 0.25) risk of renal events versus those with lower UACR levels. In conclusion, baseline UACR levels do not significantly influence the nephroprotection by SGLT2is, yet the greater protection in patients with very high UACRs in CREDENCE deserves confirmation. The underlying mechanisms of renal protection with SGLT2is might be different in patients with or without (high) UACR.

Dataset Information

The Effect of Sodium-Glucose Cotransporter Inhibitors on Renal Function as Adjunctive to Insulin in Adults with Type 1 Diabetes: An Updated Multilevel Meta-analysis of Randomized Controlled Trials.

Introduction

Methods

Results

Conclusion

Publications

The Effect of Sodium-Glucose Cotransporter Inhibitors on Renal Function as Adjunctive to Insulin in Adults with Type 1 Diabetes: An Updated Multilevel Meta-analysis of Randomized Controlled Trials.

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