Efficacy of 12-week treatment with polyethylene glycol loxenatide in obesity or overweight patients with type 2 diabetes: a multicenter, prospective cohort study based on the flash glucose monitoring system.

OBJECTIVES

To investigate the factors influencing the glucose-lowering efficacy of polyethylene glycol loxenatide (PEG-Loxe) added to diet, exercise, and existing glucose-lowering therapies in patients with poorly controlled type 2 diabetes mellitus (T2DM) after 12 weeks of treatment.

METHODS

This multicenter prospective cohort study with a pre-post intervention design, based on the FreeStyle Libre flash glucose monitoring (FGM) system, enrolled T2DM patients with inadequate glycemic control (HbA1c >7.5%) despite stable treatment (diet, exercise, and medication) for at least 8 weeks. PEG-Loxe (0.2 mg once weekly) was added to their original treatment regimen for 12 weeks. Demographic and clinical data were collected. Standardized meal tests were performed before and after treatment to measure glucose, HbA1c, insulin, C-peptide, and glucagon. Glycemic profiles, including 24-hour mean blood glucose (MBG), glucose variability (SDBG, CV), time in range (TIR), time above range (TAR), and time below range (TBR), were assessed using the hospital version of the Abbott FreeStyle Libre FGM system.

RESULTS

Of the 500 initially enrolled patients, 246 patients were included in the final analysis. Baseline HbA1c was 8.74% ± 1.07%. After 12 weeks of PEG-Loxe add-on therapy, 39.6% of patients achieved HbA1c <6.5%, 63.3% achieved HbA1c <7.0%, and 77.12% attained TIR >70%. Significant reductions were observed across multiple parameters. Fasting blood glucose (FBG), postprandial blood glucose (PBG), MBG, TAR, and SDBG were significantly reduced (all P<0.05). Concurrently, TIR, insulin levels, C-peptide levels, and insulin resistance (as measured by HOMA-IR) improved, while 2-hour postprandial glucagon (2h-PGlu) decreased. No significant change in TBR was detected. Correlation analysis revealed that TIR improvement was associated with a shorter diabetes duration and higher baseline HbA1c. Furthermore, PEG-Loxe treatment significantly improved cardiometabolic parameters and liver enzymes.

CONCLUSIONS

PEG-Loxe significantly improved glycemic control in Chinese patients with T2DM who were overweight or obese. Patients who were younger, had a shorter duration of diabetes, and presented with higher baseline glucose levels appeared to derive greater benefit from the therapy. Beyond glycemic control, PEG-Loxe might also show additional benefits across multiple cardiometabolic indices.

CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, identifier NCT05611684.