ArticlePharmacology research & perspectives2017
Novel SGLT2 inhibitor: first-in-man studies of antisense compound is associated with unexpected renal effects.
Article in Pharmacology research & perspectives, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Effects of 2'-O-Methoxyethyl Oligonucleotides on Renal Function in Humans.Nucleic acid therapeutics · 2018Pooled it
- Effects of SGLT2I Therapy on Tubular Reabsorption and Tubular Epithelial Stress Injury in Patients With CKD.Kidney medicine · 2026Article
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- Article
- Considerations in the Preclinical Assessment of the Safety of Antisense Oligonucleotides.Nucleic acid therapeutics · 2023Review
- Nephrotoxic antisense oligonucleotide SPC5001 induces kidney injury biomarkers in a proximal tubule-on-a-chip.Archives of toxicology · 2021Article
- Antisense oligonucleotide development for the selective modulation of CYP3A5 in renal disease.Scientific reports · 2021Article
- What does sodium-glucose co-transporter 1 inhibition add: Prospects for dual inhibition.Diabetes, obesity & metabolism · 2019 · on this mapReview
- Novel SGLT2 inhibitor: first-in-man studies of antisense compound is associated with unexpected renal effects.Pharmacology research & perspectives · 2017Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The antisense compound ISIS 388626 selectively inhibits renal glucose reabsorption by inhibiting the sodium-glucose cotransporter-2 (SGLT2) mRNA expression. It is developed as an insulin-independent treatment approach for type 2 diabetes mellitus (T2DM). The safety, tolerability, pharmacokinetics, and pharmacodynamics after subcutaneous administration of the drug were planned to be evaluated in healthy volunteers in a single-ascending-dose study (50-400 mg) and a multiple-ascending-dose study (6 weeks; weekly doses of 50-400 mg with loading dose regimen of three doses during the first week). The study was halted early because increases in serum creatinine occurred in the subjects participating in the 100 mg multiple-dose cohort. The pronounced changes in serum creatinine were accompanied by increased urinary excretion of beta-2-microglobulin and KIM1. The possible mechanisms for these findings remain elusive and are in contrast to preclinical findings as comparable treatment with ISIS 388626 of animals did not reveal similar changes. Although exposure was limited, there was an indication that glucosuria increased upon active treatment. Before the concept of antisense-mediated blocking of SGLT2 with ISIS 388626 can be explored further, more preclinical data are needed to justify further investigations.
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