“Clinical Bites” –⁠ Research Highlights 2025/28

Transplantation of Genetically Edited Beta Cells Without Immunosuppression

Researchers from Uppsala University in Sweden have, for the first time, transplanted genetically modified pancreatic beta cells from an allogeneic donor into a patient with type 1 diabetes (T1D)—without the need for immunosuppression. CRISPR editing and lentiviral transduction were used to prevent immune rejection. Phase I clinical trial results were published on August 4, 2025, in the New England Journal of Medicine.

In a 42-year-old man diagnosed with autoimmune T1D at age 5, just 7% of the cell volume required for curative purposes was implanted into the forearm muscle. Twelve weeks post-transplantation, persistent levels of C-peptide (a marker of insulin secretion) were detected, which had been undetectable pre-transplant. C-peptide levels responded to glucose administration. No adverse events were deemed serious or related to the treatment. MRI confirmed graft persistence of hypoimmune beta cells after 12 weeks.

Source: Carlsson P. O., Hu X., Scholz H. et al. Survival of transplanted allogeneic beta cells with no immunosuppression. N Engl J Med 2025 Sep 4; 393 (9): 887–894, doi: 10.1056/NEJMoa2503822.

Factors Influencing GLP-1RA Efficacy in Obesity Treatment

The effectiveness of GLP-1 receptor agonists (GLP-1RA) for weight loss is associated with longer treatment duration, absence of diabetes, and higher baseline body fat percentage. This was shown in a retrospective study of 679 patients with obesity/overweight who began treatment with various GLP-1RA agents, including semaglutide, liraglutide, lixisenatide, beinaglutide, exenatide, dulaglutide, and pegylated loxenatide.

Patients were categorized into 3 groups: (1) weight loss ≥5%, (2) minimal weight change (<5% loss), and (3) weight regain (after ≥5% loss) at 6 and 12 months. Greater weight loss at 12 months was linked to longer GLP-1RA use and better beta-cell function. At 6 months, greater weight loss correlated with absence of diabetes, semaglutide use, and higher initial fat percentage. Those with weight regain had significantly higher baseline eGFR than the other groups. J-shaped curves were observed in relation to initial metabolic rate, muscle mass, and abdominal/arm muscle volume.

Source: Wang J., Lin C., Cai X. et al. Glucagon-like peptide-1 receptor agonist treatment associated weight fluctuation and influencing factors in patients with overweight or obesity.