UAB diabetes researchers presented their latest work on an international stage at the 61st Annual Meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria, Sept. 15-19.
Anath Shalev, M.D., UAB Comprehensive Diabetes Center (UCDC) Director and Professor in the UAB Division of Endocrinology, Diabetes and Metabolism, and Timothy Garvey, M.D., UCDC Senior Scientist and Professor of Medicine in the UAB Department of Nutrition Sciences, shared their study results and expertise at the global diabetes conference that explored the latest advancements in diabetes research, treatment, and care. Clinical findings with ties to original UAB diabetes studies were also presented.
TXNIP and T1D
Shalev is a pioneer in the study of thioredoxin-interacting protein (TXNIP) in pancreatic islet biology and its role in diabetes. She was invited to present at the INNODIA Symposium, held in conjunction with the EASD Annual Meeting, on Sept. 15. As part of that afternoon’s “Life-changing T1D Therapies Symposium,” Shalev highlighted how specific and effective targeting of elevated TXNIP with the investigational new oral drug TIX100 could open an entirely new chapter in disease-modifying therapy in Type 1 diabetes (T1D).
The Phase 1 Single Ascending Dose (SAD) study of TIX100 completed in May successfully demonstrated safety and tolerability in humans. TIXiMED, the maker of TIX100, is now planning a Phase 1 multiple ascending dose (MAD) study to assess longer-term TIX100 safety, tolerability, and pharmacokinetics in healthy subjects and pave the way for a Phase 2 trial in individuals with T1D.
CagriSema and Obesity
Garvey, the founding principal investigator (PI) of the NIH P-30 UAB Diabetes Research Center (DRC), has achieved international recognition for his research in the metabolic, molecular, and genetic pathogenesis of insulin resistance, Type 2 diabetes, and obesity.
His latest research was published in The New England Journal of Medicine in June, which found a new combination drug therapy, known as CagriSema, is showing extraordinary promise in the bout against obesity, helping patients lose an average of 20 percent of their body weight in a major clinical trial.
CagriSema combines two hormone-based drugs—semaglutide, already approved for weight loss, and cagrilintide, which is still being studied. Cagrilintide is a long-acting form of amylin, which is normally secreted together with insulin from the pancreas, and for the first time is now being studied in a Phase 3 trial known as REDEFINE 1.
At EASD, Garvey gave two presentations related to the Phase 3 trial as part of the Sept. 16 session, “Beyond GLP-1 horizon: oral drugs, dual agonists,” and the Sept. 18 session, “It takes two to tango: news on the dual agonists.”
T1D clinical trials with UAB connections
The final day of EASD included a presentation of breaking results from the Ver-A-T1D trial using the INNODIA Master Protocol.
Thomas Pieber, M.D., Professor of Medicine, Head of the Division of Endocrinology and Metabolism and Chairman of the Department of Internal Medicine at Medical University of Graz, Austria, presented, “The effect of verapamil SR in adults with new onset stage 3 Type 1 diabetes: a multi-center, randomized, placebo-controlled trial.”
The first verapamil trial in adults with recent onset T1D was launched over a decade ago by UCDC’s clinical trial team of Shalev and Fernando Ovalle, M.D. The randomized double-blind placebo-controlled phase 2 clinical study discovered that verapamil preserved beta cell function as measured by mixed-meal stimulated C-peptide area under the curve (AUC) and reduced insulin requirements and hypoglycemic episodes. These human findings were consistent with previous preclinical data revealing the TXNIP-lowering and anti-diabetic effects of verapamil by Shalev and Guanlan Xu, Ph.D. In 2023, these beneficial effects of verapamil were further validated in children with new-onset T1D by the CLVer trial.
Now, in the Ver-A-T1D trial, verapamil conferred non-statistically significant preservation of C-peptide in recent onset T1D. The primary endpoint of mixed-meal stimulated C-peptide AUC was not met statistically when analyzed by intention to treat (p=0.06).
However, there were two dispensing errors (subjects that should have gotten verapamil got placebo and vice versa), seven discontinuations (five in the verapamil group) and 13 withdrawals, and so when analyzed per protocol, based on actual treatment received, the p-value was p=0.03 and significant.
There also was an unexpected slower/milder decline in C-peptide in the placebo group as opposed to multiple natural T1D history studies, which resulted in a smaller difference and a study not sufficiently powered to see a significant effect, Pieber concluded.
While no unexpected adverse events were noted, 46% of subjects in the verapamil group developed cardiovascular side effects including 20% first-degree AV-block and 14% bradycardia, none of which were severe.
“It is gratifying to see yet another clinical trial validating our initial findings and supporting the concept of TXNIP inhibition for the treatment of T1D, while also underlining the need for safer and more potent, effective, and specific approaches such as TIX100,” Shalev said. “Currently, TIX100 is being advanced through clinical trials by the UAB startup company TIXiMED and has recently completed its first Phase 1 trial, where it was found to be safe and well-tolerated and to already exhibit a metabolic signal.”
View the scientific program overview and abstracts on the EASD Annual Meeting site here.
The 62nd EASD Annual Meeting will take place Sept. 28-Oct. 2, 2026, in Milan, Italy.