Efficacy of DPP-4 inhibitors and SGLT2 inhibitors compared to sulphonylureas in adult patients with diabetes with low c-peptide levels with or without anti-GAD65 antibody positivity.

Abstract Background and aims Latent Autoimmune Diabetes of Adulthood (LADA) is different from type 2 diabetes. Present treatment protocols do not reflect that. DPP-4 and SGLT2 inhibitors have changed therapy. DPP-4 inhibitor use has shown delayed decline in beta-cell reserve in LADA. We studied patients with low c-peptide to assess relationship between c-peptide and anti-GAD65 antibody levels and compare DPP-4 inhibitors with SGLT2 inhibitors and sulphonylureas. Methods The study was an open-label trial conducted in 156 participants with low c-peptide (  25 years, recently diagnosed diabetes with HBA1c ≥ 6.5%. Participants were enrolled into three arms: Group A received sulphonylureas + metformin, Group B received DPP-4 inhibitors + metformin, and Group C received SGLT-2 inhibitors + metformin. Serum anti-GAD-65 antibodies were assessed using sandwich ELISA. Participants were assessed on enrolment and after three months of dual pharmacotherapy. Results The three arms were comparable on enrolment. 52% of participants with low c-peptide had high anti-GAD65 antibody titers. Significant differences were observed after three months - DPP-4 inhibitors reduced HbA1c by 1.1 ± 0.3%, compared to SGLT2 inhibitors (0.8 ± 0.13%) and sulphonylureas (0.7 ± 0.3%) Conclusion DPP-4 inhibitors appear to provide better glycemic control than alternate therapeutic options in patients with low serum c-peptide.