medwireNews: Tirzepatide may have a renoprotective effect in people with type 2 diabetes and high vascular risk, shows a prespecified analysis of SURPASS-4.
Presenting the findings at the 82nd ADA Scientific Sessions in New Orleans, Louisiana, Hiddo Heerspink (University of Groningen, the Netherlands) noted that a third of people with type 2 diabetes and cardiovascular disease also have kidney disease.
SURPASS-4 enrolled a population at high vascular risk who were already using up to three oral medications to control their blood glucose levels. The average baseline estimated glomerular filtration rate (eGFR) of the 1995 participants was around 81 mL/min per 1.73 m2, and about 18% had an eGFR below 60 mL/min per 1.73 m2. In addition, 28% had microalbuminuria and 8% macroalbuminuria.
The median urinary albumin to creatinine ratio (UACR) at baseline was 13.0 mg/g in the group randomly assigned to take insulin glargine, and during a median follow-up of 85 weeks this increased by 56.7%. By contrast, it reduced over the first 42 weeks in people taking tirzepatide, from an average of 16.8 mg/g, and then stabilized at a nonsignificant 4.4% below baseline.
During the 30 days after stopping treatment, however, UACR rose by an average of 31.0% in the tirzepatide group, and continued to rise in the glargine group.
“And this increase in albuminuria during the washout period tells me that this initial reduction in albuminuria is a real pharmacological effect,” said Heerspink.
The protective effect was seen in key renal subgroups, he added, namely people with baseline albuminuria, with moderately or severely reduced kidney function, or with a high risk for kidney-related outcomes.
In line with the UACR results, eGFR declined throughout follow-up in the glargine group, to an average of 74.0 at week 104. In the tirzepatide group there was an initial sharp decrease, after which it rose again and then declined more slowly than in the tirzepatide group, to an average of 76.0, which was significantly higher than in the glargine group. Again, the results were consistent in kidney-specific subgroups.
Of note, the beneficial effects of tirzepatide on UACR and eGFR were present regardless of whether or not the participants were taking a sodium-glucose cotransporter 2 inhibitor. About a quarter of the trial participants were doing so.
Looking at a composite endpoint of at least a 40% decline in eGFR, new-onset macroalbuminuria, progression to end-stage kidney disease, and renal death, the researchers found the risk for this to be reduced by a significant 42% with tirzepatide versus glargine, with the difference becoming apparent soon after week 40.
However, Heerspink stressed that this was mainly driven by a reduction in the risk for new-onset macroalbuminuria.
He concluded: “Collectively, these results indicate that tirzepatide may provide kidney protection, and they support future research to further evaluate the efficacy of tirzepatide in reducing kidney failure in patients with type 2 diabetes.”
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ADA Scientific Sessions; New Orleans, Louisiana: 3–7 June 2022