Semaglutide Plus Insulin Shows Benefits in LADA

Semaglutide as add-on therapy to insulin was associated with improved glycometabolic control in adults with latent autoimmune diabetes in adults (LADA), according to a retrospective study published in The Journal of Clinical Endocrinology & Metabolism.

The study evaluated patients with LADA, a form of diabetes with intermediate features between type 1 and type 2 diabetes. The authors noted that LADA is characterized by a highly variable rate of β-cell destruction and that some patients also have features of insulin resistance and obesity. The authors also noted that glucagon-like peptide-1 receptor agonists are not approved for autoimmune diabetes and that their off-label use is increasing; they described these agents as potentially attractive for patients with LADA, particularly those with preserved β-cell function.

Researchers analyzed data from 80 patients with LADA treated with oral or subcutaneous semaglutide as adjunctive therapy to insulin across several diabetes centers in Lombardia, Italy. Of these patients, 68 continued semaglutide for at least 6 months, while 12 discontinued treatment, mainly because of gastrointestinal adverse effects.

After 6 months, patients who continued semaglutide had reductions in glycated hemoglobin (HbA1c), body mass index (BMI), fasting plasma glucose, and total daily insulin dose. HbA1c decreased from 8.2% to 6.9%, BMI decreased from 26.9 kg/m2 to 25.5 kg/m2, and total daily insulin dose decreased from 42.4 IU/day to 32.4 IU/day. Time in range increased from 74.4% to 78.9%, while time below range did not significantly change.

The authors reported that some benefits, including bolus insulin reduction and time-in-range improvement, were greater among patients with preserved β-cell reserve, based on C-peptide levels. Patients with higher C-peptide values had larger reductions in bolus insulin and greater improvements in time in range. Overall, 14 of 68 patients, or 20.5%, stopped prandial insulin after starting semaglutide. No cases of diabetic ketoacidosis were recorded during follow-up.

The authors concluded that semaglutide add-on treatment was associated with beneficial effects on weight and glycometabolic control in patients with LADA, especially among those with preserved β-cell function. They also noted limitations including the study’s retrospective design, small sample size, lack of a control group, mixed semaglutide formulations, and short follow-up.

Source: Lunati ME, Cimino V, Bernasconi D, et al. The use of semaglutide as an add-on therapy in patients with latent autoimmune diabetes in adults. J Clin Endocrinol Metab. 2026;111(7):1842-1849. doi:10.1210/clinem/dgag072