Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta‐analysis

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>The present systematic review aimed to summarize the available evidence from published randomized controlled trials (RCTs) regarding the effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus.</jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p>Medline (via PubMed), Cochrane Library and Scopus were searched until 20 October 2023. Double‐independent study selection, data extraction and quality assessment were performed. Evidence was pooled with a three‐level mixed‐effects meta‐analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In total, 9533 participants from eight RCTs were analysed. All RCTs had a low risk of bias, according to the Cochrane Collaboration tool (RoB2). Tirzepatide was associated with a significantly greater reduction in urine albumin‐to‐creatinine ratio compared with controls [mean difference (MD) −26.9%; 95% confidence interval (CI) (−34.76, −19.04); <jats:italic>p</jats:italic> < .001; level of evidence (LoE) moderate]. This effect remained significant in participants with baseline urine albumin‐to‐creatinine ratio ≥30 mg/g [MD −41.42%; 95% CI (−54.38, −28.45); <jats:italic>p</jats:italic> < .001; LoE moderate]. Based on subgroup analysis, the comparative effect of tirzepatide was significant against placebo and the insulin regimen, whereas no difference was observed compared with semaglutide. The beneficial effect of tirzepatide on albuminuria levels remained significant across all investigated doses (5, 10 and 15 mg), showing a dose‐response relationship. A neutral effect was observed on the estimated glomerular filtration rate [MD 0.39 ml/min/1.73m<jats:sup>2</jats:sup>; 95% CI (−0.64, 1.42); <jats:italic>p</jats:italic> = .46; LoE moderate].</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our findings suggest that tirzepatide probably leads to a significant reduction in albuminuria across all administered doses, while its use is associated with a neutral effect on creatinine clearance as a measure of renal function.</jats:p></jats:sec>