Novel antidiabetes drugs improve composite renal outcomes
The beneficial effects of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on diabetes-related cardiovascular and renal outcomes were established in major cardiovascular outcome trials (CVOTs) in people with type 2 diabetes. These glucose-lowering drugs have also been shown to be effective in people without type 2 diabetes, and have now become an integral part of many treatment guidelines.
Despite the wealth of published data, the absolute treatment benefits (expressed as number needed to treat [NNT]) of GLP-1 RAs and SGLT2is on renal outcomes remain uncertain. The present retrospective meta-analysis aimed to display and compare the NNT of both drug classes for a composite renal outcome.
Individual patient time-to-event information on composite renal outcomes was digitised from Kaplan–Meier plots of major CVOTs comparing SGLT2is or GLP-1 RAs to placebo. To achieve absolute risk differences of both treatment groups, parametric Weibull regression models were fitted for all trials separately. Trials that did not include Kaplan–Meier plots, or where the extracted HRs from the Weibull models diverged significantly from the originally reported HRs, were excluded. Random-effects meta-analysis were carried out for each monthly follow-up time point and summarised to generate meta-NNTs for the two drug classes.
In total, information from 90,865 patients was extracted for analysis across twelve CVOTs (three GLP-1 RAs and nine SGLT2is). Eight trials took place in primary type 2 diabetes populations, two in primary heart failure and two in primary chronic kidney disease. Overall median follow-up time was 35.8 months. Mean eGFR at baseline ranged from 37.3–85.3 mL/min/1.73 m². Although the definition of composite renal endpoint varied, all included pre-specified increase in serum creatinine/decrease in eGFR and incident end-stage kidney disease or renal replacement therapy.
A total of 6199 (6.8%) participants experienced a composite renal event. Estimated meta-NTT for the prevention of a single event was 85 (95% CI, 60–145) for GLP-1 RAs and 104 (81–147) for SGLT2is, at the overall median follow-up of 36 months.
The investigators conclude that there are moderate and similar absolute treatment benefits of GLP-1 RAs and SGLT2is compared to placebo for a composite renal outcome. Their analysis could not identify a greater advantage on composite renal outcomes for either class of drug; however, this may have been affected by the heterogenous nature of the baseline data. Similar trials of GLP-1 RAs where pre-existing impaired renal function is the primary inclusion criteria are not currently available and represent an important area of future research.
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