Addition of Metformin to Insulin on the Decline Rate of β-cell Function in Non-obese Patients with Latent Autoimmune Diabetes in Adults: A Three-year Open-labeled Pilot Study

Aims: As one of the most popular anti-diabetic drug, metformin has been applied to type 1 diabetes mostly limited to obese patients. However, its effect on β-cell function in non-obese autoimmune diabetes is less defined. Latent autoimmune diabetes in adults (LADA) serves as a good model with the phenotype between type 1 and type 2 diabetes, and non-obese LADA is a subtype more prone to the former. The aim of this study is to investigate the effect of metformin plus insulin on β-cell function in non-obese LADA patients. Methods: Twenty non-obese LADA patients were randomized 1:1 to receive insulin therapy with 500-850mg metformin twice a day (n=10) or insulin alone (n=10) for 3 years. Residual β-cell function was evaluated with fasting C-peptide (FCP) and 2-hour postprandial C-peptide (2-hour CP) in a mixed meal tolerance test (MMTT). delta CP (delta CP = 2-hour CP-FCP) and area under the curve of C-peptide (AUCC) were calculated accordingly. Results: The baseline data of two groups were well-matched with no statistical difference. During the 3-year treatment, no significant differences were detected in glycemic control and metabolic profiles between two groups. Different from insulin alone group that FCP, 2-hour PCP, delta CP and AUCC were significantly decreased during the 3-year treatment (P< 0.05), the levels of FCP, 2-hour PCP, delta CP and AUCC sustained in the metformin plus insulin group (P>0.05). There is no significant difference between two groups in FCP, 2-hour CP, delta CP or AUCC (P>0.05). Conclusions: Combination of metformin and insulin may help to slow down the decline rate of β-cell function in non-obese LADA patients.