Tirzepatide significantly lowers albuminuria across all administered doses in patients with type 2 diabetes: Study

“In patients with type 2 diabetes mellitus (T2DM), tirzepatide showed a significant and dose-dependent reduction in urine albumin-to-creatinine ratio,” the researchers reported.

“The reduction in albuminuria was consistent across all doses (15, 10, and 5 mg), highlighting a dose-response relationship.”

The researchers showed a neutral effect on the estimated glomerular filtration rate (eGFR), indicating no adverse impact on renal function.

Paschalis Karakasis, Aristotle University of Thessaloniki, General Hospital “Hippokration”, Thessaloniki, Greece, and colleagues aimed to summarize the available evidence from published randomized controlled trials (RCTs) regarding the effect of tirzepatide on renal function and albuminuria levels in patients with type 2 diabetes in a systematic review.

For this purpose, the researchers searched the online databases until 20 October 2023. They performed double-independent study selection, data extraction and quality assessment. Evidence pooling was done with a three-level mixed-effects meta-analysis. The analysis included 9533 participants from eight RCTs.

The researchers reported the following findings:

• 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%; level of evidence (LoE) moderate]. This effect remained significant in participants with baseline urine albumin-to-creatinine ratio ≥30 mg/g [MD −41.42%; 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/1.73m2; LoE moderate].

“Our results 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 kidney function,” the researchers concluded.

Reference:

Karakasis P, Patoulias D, Fragakis N, Klisic A, Rizzo M. Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta-analysis. Diabetes Obes Metab. 2023 Dec 20. doi: 10.1111/dom.15410. Epub ahead of print. PMID: 38116693.