Aims: To examine the albuminuria-lowering effect of exenatide once weekly (EQW) compared with active glucose-lowering comparators in patients with type 2 diabetes and elevated urinary 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-glucagon-like peptide-1 receptor agonist comparators in patients with type 2 diabetes 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 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% confidence interval [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 renin-angiotensin system inhibitor usage. Adjusted mean decreases in HbA1c, SBP and body weight 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 body weight, the uACR-lowering effect was reduced to (−13.0% [95% CI −29.9 to 7.8]). Conclusion: Exenatide once weekly reduced uACR in patients with type 2 diabetes and elevated albuminuria compared to commonly used glucose-lowering drugs.