Polyethylene Glycol Loxenatide Selectively Reduces Adiposity While Preserving Lean Body Mass in Type 2 Diabetes: A...

To investigate the effects of polyethylene glycol loxenatide (PEX168) on visceral and body fat, as well as glycolipid metabolism, in patients with type 2 diabetes mellitus (T2DM).

A prospective interventional study design was adopted. A total of 100 patients with type 2 diabetes mellitus (T2DM) who visited the outpatient clinic of the Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, between January and December 2023 were enrolled. On the basis of their original glucose-lowering regimen, polyethylene glycol loxenatide (PEX168) 0.2 mg was administered subcutaneously once weekly for 12 weeks. Ninety-nine patients (68 males, 31 females; mean age 53.48 ± 11.36 years) completed the 12-week treatment, while one patient was lost to follow-up. Among them, 16 patients extended treatment to one year. Glycemic parameters [glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG)], continuous glucose monitoring profiles, and 25-hydroxyvitamin D (25-OH-VD) levels were assessed before and after treatment. Body composition, including visceral fat area (VFA), skeletal muscle mass, and lean body mass, was measured using bioelectrical impedance analysis. Paired t-test or Wilcoxon signed-rank test was used to compare differences before and after treatment.

After 12 weeks of treatment compared with baseline, improvements were observed in glycosylated hemoglobin (8.8 ± 1.11% vs 6.9 ± 0.92%, P < 0.001), fasting blood glucose (9.6 ± 2.65 mmol/L vs 7.2 ± 1.71 mmol/L, P < 0.001), body weight (75.5 ± 12.67 kg vs 74.7 ± 12.78 kg, P = 0.003), BMI (27.1 ± 3.03 kg/m² vs 26.8 ± 3.05 kg/m², P = 0.025), body fat mass (23.9 ± 6.12 kg vs 23.0 ± 5.86 kg, P = 0.002), VFA (120.0 ± 36.04 cm² vs 113.7 ± 32.90 cm², P = 0.001), and 25-OH-VD levels (48.88 [41.99, 57.88] nmol/L vs 51.60 [45.55, 64.17] nmol/L, P = 0.002). Lean body mass (LBM) remained unchanged.

PEX168 treatment for 12 weeks not only effectively improves glycemic control, lipid profiles, and glycemic variability in patients with T2DM, but also significantly reduces visceral fat, ameliorates central obesity, and preserves skeletal muscle mass, thereby achieving "high-quality weight loss.".

www.clinicaltrials.gov identifier is NCT05611684.