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Exenatide once weekly decreases urinary albumin excretion in patients with type 2 diabetes and elevated albuminuria: pooled analysis of randomized active controlled clinical trials.

AIMS: Data regarding the albuminuria-lowering effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with diabetes and chronic kidney disease are limited. We examined the albuminuria-lowering effect of exenatide once weekly (EQW) compared with active glucose-lowering comparators in patients with type 2 diabetes (T2D) and increased urine albumin-to-creatinine ratio (uACR).

METHODS: Six randomized double-blind and open-label phase III studies were pooled in a post-hoc, exploratory analysis to evaluate the efficacy and safety of EQW versus non-GLP1 comparators in patients with T2D and baseline uACR ≥30 mg/g. Treatment groups were EQW versus all comparators pooled. Efficacy outcomes were percent change from baseline to week 26/28 in uACR and absolute change in glycated haemoglobin (HbA1c), systolic blood pressure (SBP), body weight (BW) and estimated glomerular filtration rate (eGFR).

RESULTS: Baseline characteristics were generally similar between the two treatment groups (EQW: N = 194, All comparators: N = 274). Relative to the comparator group, EQW changed albuminuria by -26.2% (95% CI -39.5 to -10). Similar improvements were observed with EQW versus oral glucose-lowering drugs (-29.6% [95% CI -47.6 to -5.3) or insulin (-23.8% [95% CI -41.8 to -0.2]). The effect of EQW on uACR was independent of baseline RASi usage. Adjusted mean decreases in HbA1c, SBP and BW were more pronounced in the EQW versus the comparator group. Adjustment for changes in HbA1c, eGFR and SBP did not substantially affect the uACR-lowering effect of EQW. When also adjusting for changes in BW, the uACR lowering effect was reduced to -13.0% [95% CI -29.9 to 7.8].

CONCLUSION: EQW reduced uACR in patients with T2D and elevated albuminuria compared to commonly used glucose-lowering drugs. This article is protected by copyright. All rights reserved.

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