Three therapeutic lines in development — SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists — highlighted at the 37th National Congress of the Spanish Diabetes Society Foundation (FSED), held on April 15-17 in Seville, Spain.

David Cherney , PhD, professor in the Department of Medicine at the University of Toronto, Toronto, Canada, and senior scientist at the Toronto General Hospital Research Institute, delivered the opening lecture at the FSED annual meeting on managing renal and cardiovascular disease in type 1 diabetes (T1D). Cherney, leading clinical investigator in the field, reviewed ongoing pharmacologic advances and urged that the therapeutic armamentarium for T1D be brought closer to what is available for patients with type 2 diabetes (T2D).

He opened by noting that “while in T2D we now have four established pharmacologic pillars to slow progression of chronic kidney disease — renin-angiotensin-aldosterone system blockers, SGLT2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, and GLP-1 receptor agonists — in T1D, the only treatment with robust evidence remains blockade of the renin-angiotensin axis, established with the captopril trial in 1993.” “So we’ve gone nearly 30 years without advances,” Cherney said, recalling that the allopurinol trial aimed at lowering uric acid — the only notable trial since then — produced neutral results around 2020.

This gap reflects the methodological challenges of studying a rare disease — and an even rarer subgroup with clinically significant nephropathy. “We will never have a 5000-patient trial in T1D with high albuminuria. There simply aren’t enough centers or patients,” he acknowledged, arguing that intermediate endpoints — particularly reductions in albuminuria and the slope of decline in glomerular filtration rate (GFR) — should be accepted as valid regulatory bases for new indications.

SGLT2 Inhibitors: The Sugar and Salt Trial

Cherney noted that the renal physiology of SGLT2 inhibitors is essentially the same in type 1 and T2D: By enhancing tubuloglomerular feedback, they reduce glomerular hyperfiltration through afferent-arteriole constriction, with benefits on albuminuria and renal function shown in animal models and mechanistic human studies. However, prior clinical programs of sotagliflozin, dapagliflozin, and empagliflozin — which were designed around glycemic endpoints — did not achieve regulatory approval for T1D because they roughly tripled the risk for diabetic ketoacidosis vs placebo.

To address that obstacle, Cherney’s team is leading the Sugar and Salt trial, which evaluates sotagliflozin — a dual SGLT1/SGLT2 inhibitor — in patients with T1D who have moderate-to-advanced nephropathy, defined by a GFR of 20-60 mL/min/1.73 m² and a urinary albumin-to-creatinine ratio (UACR) of at least 100 mg/g. The investigators hypothesize that in this population the glucosuric effect — and therefore the risk for diabetic ketoacidosis — will be minimal, while the drugs’ renal hemodynamic benefit remains intact. The trial’s primary endpoint is GFR measured after a washout period following three years of treatment — an endpoint the FDA has recently endorsed as valid. The study is already more than two thirds recruited across over 20 centers in Canada and the US.

Finerenone in T1D

The second focus was the nonsteroidal mineralocorticoid receptor antagonist finerenone, whose efficacy in T2D was established in the FIGARO-DKD trial and the FIDELIO-DKD trial, with a 23% reduction in the composite renal primary endpoint and roughly a 30% reduction in albuminuria.

Cherney presented results from the FINE-ONE trial, recently published in The New England Journal of Medicine and previously presented at the American Society of Nephrology (ASN) meeting. The primary endpoint was reduction in albuminuria at 6 months. FINE-ONE showed a mean UACR reduction of 28% vs placebo, with an average 25% reduction sustained during treatment. Cherney called that “clinically relevant,” noting that “UACR reductions of 25%-30% or more strongly associated with less long-term progression to kidney failure.” When the drug was stopped, albuminuria rebounded by about 10%, suggesting a hemodynamic contribution to the mechanism in addition to anti-inflammatory and antifibrotic effects, he explained.

From a safety standpoint, the absolute increase in hyperkalemia leading to drug discontinuation was 1%-2%, comparable to the rates seen in T2D trials and far below the 15%-20% historically observed with spironolactone.

Cherney called these results “the first real advance in nephrology for T1D” and said he is already considering compassionate-use finerenone for patients with significant albuminuria who lack other therapeutic options.

GLP-1 Receptor Agonists: From the FLOW Trial to T1D

The third therapeutic line was GLP-1 receptor agonists, an area Cherney described as “extraordinarily dynamic.” He reviewed findings from the FLOW trial — the only trial with a renal primary endpoint evaluating subcutaneous semaglutide in T2D — which was stopped early for efficacy and presented in spring 2024: a 24% reduction in the composite renal primary endpoint, preservation of renal function by 1.16 mL/min per year, an 18% reduction in major adverse cardiovascular events, and a reduction in all-cause mortality. In Canada, the indication for chronic kidney disease was approved in the summer of 2025.

To explore mechanisms, Cherney described the REMODEL mechanistic substudy, which includes BOLD MRI, serial renal biopsies, and multiple biomarkers. Secondary results presented at ASN showed reductions in perirenal fat (25%) and renal sinus fat (13%), a decrease in renal artery resistive index, stabilization of cortical renal stiffness (a marker of fibrosis), a 40% reduction in albuminuria and evidence of endothelial reprogramming with suppression of metabolic stress genes and natural killer cell signatures in the tubular interstitium. The SMART trial, in 106 nondiabetic patients, also demonstrated a 52% reduction in albuminuria with high-dose semaglutide, reinforcing a glucose-independent, intrinsic renal effect of the drug.

Regarding T1D, Cherney announced the pilot REMODEL T1D study, a 6-month mechanistic trial of semaglutide in patients with T1D and nephropathy (albuminuria categories A2-A3 and GFR ≥ 30 mL/min/1.73 m²), with nearly two thirds of patients already randomized. Its results will determine whether the renal protective mechanisms are replicated in this population and will guide the design of a larger trial.

He also presented the AQUATICA trial, which will evaluate the dual GLP-1 or glucose-dependent insulinotropic polypeptide agonist CT-868 in 600 patients with T1D.

A Horizon of Transformation

Cherney closed by emphasizing that “diabetic nephrology in T2D has, by adding each new drug class, progressively slowed the slope of GFR decline to the point that many patients now reach renal stability and can return to primary care follow-up.” The challenge now is to reproduce that transformation in T1D. “The mechanisms are the same; the physiology is the same. What we lack is the completed trials,” he concluded.

In the subsequent discussion, Cherney highlighted albuminuria level as “the main stratification and enrichment factor for trials” and cardiovascular risk as “a second dimension of selection that has been insufficiently explored in T1D.”

This article was translated from El Médico Interactivo, part of the Medscape Professional Network.