Polyethylene glycol loxenatide injections added to metformin effectively improve glycemic control and exhibit favorable safety in type 2 diabetic patients

Diabetes Obesity Metabolism

et al. 2020

Self Cite

Aim To evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) monotherapy in type 2 diabetes (T2D) patients in China. Materials and Methods In a multicentred, randomized, double‐blinded, placebo‐controlled phase 3a clinical trial, 361 patients with inadequate glycaemic control (HbA1c 7.0%‐10.5%, fasting plasma glucose <13.9 mmol/L) were randomized (1:1:1) for weekly subcutaneous injections: placebo, PEX168/100 μg or PEX168/200 μg. The 24‐week treatment was followed by a 28‐week extension, during which placebo‐treated patients were randomly assigned to PEX168/100 μg or PEX168/200 μg. The primary efficacy endpoint was the HbA1c change from baseline to week 24. Results The three groups had similar demographics and baseline characteristics. The HbA1c least‐square mean (95% CI) change from baseline to week 24 was greater for PEX168/100 μg (−1.02% [−1.21%, −0.83%]) and PEX168/200 μg (−1.34% [−1.54%, −1.15%]) than for placebo (−0.17% [−0.36%, 0.02%]); (superiority: P < .0001). The proportions of patients with less than 7% HbA1c in the placebo, PEX168/100 μg and PEX168/200 μg groups were 15.7%, 34.7% and 46.6%, respectively. Common gastrointestinal adverse events (AEs) were nausea (5.6%, 10.0% and 0% for PEX168/100 μg, PEX168/200 μg and placebo, respectively) and vomiting (2.4%, 8.3% and 0% for PEX168/100 μg, PEX168/200 μg and placebo, respectively). Six (1.6%) patients (PEX168/100 μg: N = 2 [1.6%], PEX168/200 μg: N = 3 [2.5%] and placebo: N = 1 [0.8%]) discontinued treatment because of AEs. Four (1.2%) patients (PEX168/100 μg: N = 3 [2.5%] and PEX168/200 μg: N = 1 [0.9%]) developed PEX168 antidrug antibodies. Conclusion PEX168 monotherapy significantly improved glycaemic control in T2D patients with a safety profile resembling that of other glucagon‐like peptide‐1 receptor agonists.

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of polyethylene glycol loxenatide monotherapy in type 2 diabetes patients: A multicentre, randomized, double‐blind, placebo‐controlled phase 3a clinical trial

Shi

Yang

Diabetes Obesity Metabolism

et al. 2020

Self Cite

“…2014 24 Exenatide: 142/Insulin: 138; Pioglitazone: 136 China 48 newly diagnosed Exenatide: 49.89 (9.64)/Insulin: 51.39 (9.65); Pioglitazone: 49.66 (8.86) Exenatide: 32.7/Insulin: 38.6; Pioglitazone: 44.9 25.9 (0.3) Insulin: 25.4 (0.3); Pioglitazone: 25.9 (0.3) Exenatide 5 ug BID (4 weeks) and 10 ug BID (44 weeks) Insulin Lispro 25 R BID; or Pioglitazone 30 mg QD (4 weeks) and 45 mg QD (44 weeks) Chen et al . 2017 18 PEX 168 100ug: 41; PEX 168 200 ug: 39/Placebo: 38 China 12 PEX 168 100 ug: 4.4 (6.4); PEX 168 200 ug: 4 (5.7)/Placebo: 6.5 (7.9) PEX 168 100 ug: 52.6 (8.4); PEX 168 200 ug: 49.8 (10.9)/Placebo: 53.5 (10.2) PEX 168 100 ug: 46.34; PEX 168 200 ug: 43.59/Placebo: 31.58 PEX 168 100 ug: 27.2 (3.6); PEX 168 200 ug: 26.3 (3.3) 27.2 (4.5) PEX 168 100 ug QW or 200 ug QW + Glucophage 1500 mg/d Placebo + Glucophage 1500 mg/d Gao et al . 2009 25 234/232 China (Mainland and Taiwan), India, Korea 16 8 (6)/8 /(5) 55 (9)/54 (9) 52/59 26.4 (3.2) 26.1 (3.4) Exenatide 5 ug BID (4 weeks) and 10 ug BID (12 weeks) + metformin ± sulphonylureas Placebo + metformin ± sulphonylureas Inagaki et al .…”

Section: Resultsmentioning

confidence: 99%

Glucagon-like peptide-1 mimetics, optimal for Asian type 2 diabetes patients with and without overweight/obesity: meta-analysis of randomized controlled trials

Fang

Tang

et al. 2017

Sci Rep

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are desirable for diabetes, especially in patients with overweight/obesity. We aimed to determine whether GLP-1RAs exhibit different glucose-lowering efficacies between Asian type 2 diabetes (T2D) patients with and without overweight/obesity. Randomized controlled trials were searched in EMBASE, MEDLINE, CENTRAL, and ClinicalTrials.gov. Studies published in English with treatment duration ≥12 weeks and information on HbA1c changes were included. The studies were divided into normal body mass index (BMI) and overweight/obese groups according to baseline BMI. Among 3190 searched studies, 20 trials were included in the meta-analysis. The standardized mean differences in HbA1c change, fasting glucose change, and postprandial glucose change were equivalent between normal BMI and overweight/obese studies (p > 0.05). The relative risk of HbA1c < 6.5% target achievement in normal BMI trials (7.93; 95% confidence interval: 3.27, 19.20) was superior to that in overweight/obesity trials (2.23; 1.67, 2.97), with a significant difference (p = 0.020). Body weight loss (p = 0.572) and hypoglycemic risk(p = 0.920) were similar in the two groups. The glucose-lowering effects of GLP-1RAs were equivalent among Asian T2D patients. With their advantages for weight-loss or weight-maintenance, GLP-1RAs are optimal medicines for Asian T2D patients with and without overweight/obesity.

“…Polyethylene glycol (PEG) loxenatide (PEX168) is a novel longacting GLP-1 RA. 15,16 Half-life extension strategies rely on sequential modification and PEGylation. This PEGylation approach delays the degradation of PEX168 by dipeptidyl peptidase-4 (DDP-4), reduces antigen immunity, delays kidney excretion because of higher molecular weight, and increases hydrophilicity, therefore prolonging the half-life and action time of PEX168 when compared with other GLP-1RAs.…”

Section: Introductionmentioning

confidence: 99%

“…This PEGylation approach delays the degradation of PEX168 by dipeptidyl peptidase-4 (DDP-4), reduces antigen immunity, delays kidney excretion because of higher molecular weight, and increases hydrophilicity, therefore prolonging the half-life and action time of PEX168 when compared with other GLP-1RAs. 15,16 The mean half-life of PEX168 is 131.8-139.8 hours, with steady-state plasma concentrations after 4 weeks. 16 The pharmacokinetics of PEX168 allows longer dosing intervals and a lower number of injections, 15,16 which are suggested to improve patient compliance.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of polyethylene glycol loxenatide as add‐on to metformin in patients with type 2 diabetes: A multicentre, randomized, double‐blind, placebo‐controlled, phase 3b trial

Gao

Diabetes Obesity Metabolism

et al. 2020

Self Cite

Aim: To assess the efficacy and safety of polyethylene glycol loxenatide (PEX168), a new glucagon-like peptide-1 receptor agonist, as an add-on to metformin therapy in Chinese patients with type 2 diabetes (T2D). Materials and methods: This was a multicentre, randomized, double-blind, placebocontrolled phase 3b trial. After metformin monotherapy (≥1500 mg/day) for 8 weeks or more, patients with uncontrolled T2D (HbA1c of 7.0%-10.5%) from 44 sites were randomized (1:1:1) to metformin + placebo, metformin + PEX168 100 μg, and metformin + PEX168 200 μg. The core treatment period lasted for 24 weeks, followed by a 28-week extension period. The primary endpoint was the change in HbA1c levels at week 24. The main secondary endpoint was the proportion of patients with an HbA1c of less than 7.0% at week 24. Results: The least-square mean (standard error) change in HbA1c levels was significantly greater (P < .001 for superiority) in the PEX168 groups (−1.16% [0.08%] and −1.14% [0.08%] with 100 and 200 μg, respectively) than in the placebo group (0.35% [0.08%]). The proportion of patients with an HbA1c of less than 7.0% at week 24 was significantly higher in the PEX168 100 μg (37.4%) and PEX168 200 μg (40.6%) groups than in the placebo group (16.8%; both P < .001). The gastrointestinal reactions were mild; the risks of hypoglycaemia and weight gain did not increase. Anti-PEX168 antibodies were noted in less than 2% of patients. No treatment-emergent serious adverse events occurred. Conclusion: The subcutaneous injection of PEX168 once a week can effectively, continuously and safely improve HbA1c levels in patients with T2D when combined with metformin.