Highlight
• Semaglutide significantly improves glycemic control in patients with latent autoimmune diabetes in adults (LADA) when added to insulin therapy.
• Treatment leads to reductions in glycated hemoglobin (HbA1c), body mass index (BMI), and total daily insulin dose.
• Patients with preserved β-cell function exhibit greater benefits, including increased time-in-range glucose metrics.
• Semaglutide allows a subset of patients to discontinue prandial insulin boluses while maintaining improved metabolic control.
Study Background
Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes that manifests in adulthood with features overlapping type 1 and type 2 diabetes. Patients typically develop gradual β-cell destruction resulting in progressive insulin deficiency, but with a slower course compared to classical type 1 diabetes. Managing LADA poses a therapeutic challenge because optimal glycemic control often requires insulin therapy early, yet residual β-cell function may persist and could be preserved with suitable treatment strategies.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide have demonstrated efficacy in type 2 diabetes through glucose-dependent insulin secretion augmentation, appetite suppression, and weight reduction. However, data on their role in LADA are limited. Considering semaglutide’s benefits and mechanisms, investigating its use as an adjunct to insulin in LADA patients may offer insight into improved management strategies.
Study Design
This retrospective study included 80 patients diagnosed with LADA who were treated with semaglutide as an add-on therapy to their ongoing insulin regimen. Patients received semaglutide either orally or via subcutaneous injections. Clinical and biochemical markers, including glycated hemoglobin (HbA1c), body mass index (BMI), serum C-peptide levels reflecting β-cell function, and insulin dose requirements, were collected. Continuous glucose monitoring (CGM) metrics, particularly time-in-range and hypoglycemia events, were analyzed when available.
Key Findings
Among the 80 patients enrolled, 68 (85%) continued treatment for at least six months, with 57 using the oral semaglutide formulation and 11 the subcutaneous form. Twelve patients discontinued therapy, though specific reasons for discontinuation were not detailed in the report.
At six months, semaglutide users showed statistically significant improvements in several key parameters:
- HbA1c reduction: A meaningful decrease in glycated hemoglobin levels indicated improved overall glycemic control.
- BMI reduction: Body mass index decreased, reflecting weight loss benefits known for GLP-1RAs.
- Insulin dose sparing: Total daily insulin requirements declined, suggesting enhanced endogenous insulin activity or improved insulin sensitivity.
- Increase in serum C-peptide levels: This finding suggests that semaglutide may help preserve or enhance residual β-cell function in LADA patients.
- Improved CGM metrics: Time-in-range (percentage of time glucose levels remain within target range) increased without a rise in hypoglycemia episodes (time below range), indicating safer and more stable glycemic profiles.
Importantly, subgroup analyses revealed that patients with preserved β-cell function (as indicated by higher baseline C-peptide) experienced greater clinical benefits: more pronounced reductions in BMI and insulin requirements and enhanced time-in-range improvements. Furthermore, 14 patients were able to discontinue insulin bolus (prandial) injections during follow-up, substituting semaglutide’s glucose-dependent insulinotropic effects, thereby reducing treatment burden.
Expert Commentary
These findings add valuable evidence supporting the use of semaglutide in LADA—a patient group often neglected in clinical trials focused separately on type 1 or type 2 diabetes. The mechanism by which semaglutide promotes weight loss and enhances β-cell function preservation aligns with its observed clinical benefits in this study.
While the retrospective design and absence of a control group limit definitive conclusions, the study highlights clinically meaningful outcomes consistent with the pharmacodynamics of GLP-1RAs. The fact that patients with preserved β-cell function derived greater benefit underscores the importance of early intervention in LADA before advanced β-cell loss.
Safety data were not extensively addressed but the unchanged hypoglycemia burden supports a favorable risk profile of semaglutide in combination with insulin.
Conclusion
In LADA patients, semaglutide as an adjunct to insulin therapy offers significant improvements in glycemic control, weight management, and insulin requirement reduction. Patients with residual β-cell function particularly benefit, showing enhanced glucose stability and potential for insulin regimen simplification. Future prospective randomized controlled trials are warranted to confirm these findings and define optimal treatment protocols. This study suggests semaglutide could play a transformative role in personalized LADA management, bridging the gap between autoimmune β-cell preservation and metabolic control.
Funding and ClinicalTrials.gov
The article did not report funding sources or clinical trial registration information.
References
1. 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. The Journal of Clinical Endocrinology and Metabolism. 2026;111(7):1842-1849. PMID: 41729594.
2. American Diabetes Association. 6. Glycemic Targets: Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S97-S110.
3. Davies MJ, D’Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2022. Diabetes Care. 2022;45(9):2753-2786.
4. Orabona L, Groppelli A, Pastorino A, et al. Characteristics of latent autoimmune diabetes in adults: coexistence of insulin resistance and autoimmune features can modify the clinical phenotype. Diabetes Care. 2018;41(7):1423-1431.