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, Fei; Lv, Xiaoyi; Zhang, Mo; Ma, Jianhua; Zhang, Qiu; Yang, Gangyi; Liu, Weijuan; Li, Quanmin; Zhou, Jian; Bao, Yuqian; Jia, Weiping

doi:10.1111/dom.14163

Cited by 20 publications

(32 citation statements)

References 34 publications

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“…Since there are limited drugs to treat obesity patients and GLP-1RAs have the effect on reducing body weight, it is necessary to study the effect of PEX-168 on weight and blood glucose in simple obesity patients, which can provide relevant data reference for weight loss field. A number of studies have confirmed the safety and efficacy of PEX-168 in patients with T2DM [ 9 , 13 ], while whether PEX-168 can bring a weight loss effect in patients with simple obesity under normal control of blood glucose has not been reported yet.…”

Section: Discussionmentioning

confidence: 99%

“…It is the first self-developed long-term GLP-1 RA in China. PEX-168 can avoid the rapid degradation of DPP-4 enzymes and slow down the metabolism of losenatide and prolong the action time in vivo through the modification of polyethylene glycol, so as to improve the efficacy of the drug [ 9 , 10 ]. The clinical recommended dose for adults with diabetes starts from 0.1 mg, and the effective dose in rats starts from 0.03 mg/kg.…”

Section: Introductionmentioning

confidence: 99%

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Polyethylene Glycol Loxenatide (PEX-168) Reduces Body Weight and Blood Glucose in Simple Obese Mice

Guo

Wang³

et al. 2021

International Journal of Endocrinology

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Background. At present, there is a lack of drug treatment for obese patients, so it is needed to find a drug that is effective and has few side effects to treat obesity. PEX-168 is a novel long-acting glucagon-like peptide-1 receptor agonist for T2DM. It improves blood glucose with fewer side effects. The aim of the present study was to investigate the effect of PEX-168 on blood glucose and body weight of mice with simple obesity. Methods. Thirty healthy and 6-week-old C57BL/6 male mice were randomly divided into a normal control group (NC, n = 6) and obesity model group (n = 24). The obesity model mice were randomly divided into a high-fat diet group (HF) and intervention groups with different doses of PEX-168 (0.03 mg/kg, 0.1 mg/kg, and 0.3 mg/kg). Each group includes 6 mice. Body weight, food intake, and fasting blood glucose (FBG) were evaluated after intraperitoneal injection, and the intervention was performed weekly for 12 weeks. Fasting insulin (FINS) levels were measured at the 12th week. Results. Compared with HF, the food intake of mice in the intervention groups decreased transiently, but there was no difference between different doses ( P > 0.05 ). The body weight of mice in the middle and high dose of PEX-168 intervention groups decreased significantly, and the differences were statistically significant ( P < 0.05 ). The administration of PEX-168 can effectively improve the blood glucose of obese mice, the difference was statistically significant ( P < 0.05 ), but there was no difference between different doses ( P > 0.05 ). At the 10th week, the incidence of transient hypoglycemia was 67% and 50% in the middle- and high-dose groups, respectively. The levels of serum FINS in the intervention groups were significantly lower than those in the HF group, and the differences were statistically significant ( P < 0.05 ), but there was no difference between different doses ( P > 0.05 ). Conclusions. PEX-168 showed significant improvement in the FBG and FINS levels of simple obese mice. Middle and high doses of PEX-168 could reduce the weight of simple obese mice, but there was a certain risk of hypoglycemia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polyethylene Glycol Loxenatide (PEX-168) Reduces Body Weight and Blood Glucose in Simple Obese Mice

Guo

Wang³

et al. 2021

International Journal of Endocrinology

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“…The studies were considered eligible for inclusion if they (1) were randomized clinical trials; (2) were conducted on individuals with type 2 diabetes mellitus; (3) compared GLP-1RAs of interest with each other or with a control group (restricted to placebo or no treatment) with or without the same add-on therapy in all arms; (4) had a follow-up between 24 and 30 weeks; (5) contained results of at least one of the prespecified primary and secondary endpoints; and (6) were published in English language. The final list of included studies was manually supplemented with two studies on loxenatide (Table S4) [14][15][16]. [17].…”

Section: Study Identificationmentioning

confidence: 99%

Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Network Meta-analysis

et al. 2021

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Introduction: The present study aimed to evaluate the effects of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on clinical and safety outcomes including glycemic control and cardiometabolic indicators using network metaanalysis. Methods: MEDLINE, Embase, and Cochrane Library Central Register of Controlled Trials were searched from inception through June 30, 2019. Randomized clinical trials comparing one or more of six eligible GLP-1RAs with placebo or another eligible GLP-1RA were identified. We further screened studies that had 24-30 week follow-up periods and target endpoints. The primary outcome was change in hemoglobin A 1c (HbA 1c). Secondary outcomes included additional glycemic control indicators, cardiometabolic measures, and adverse events. Frequentist random-effect network meta-analyses were conducted for effect comparison. Results: The NMA synthesized evidence from 54 studies covering 23,209 patients and 18 GLP-1RA regimens. All included GLP-1RA regimens except liraglutide 0.3 mg once weekly (QW) significantly lowered HbA 1c after 24-30 weeks compared with placebo. The pairwise comparison of HbA 1c-lowering effect showed that dulaglutide 0.75 mg QW, dulaglutide 1.5 mg QW, exenatide 2 mg QW, liraglutide 0.9 mg QW, liraglutide 1.2 mg QW, liraglutide 1.8 mg QW, loxenatide 100 lg QW, and loxenatide 200 lg QW were not significantly outperformed by any of the other regimens. The effects on blood pressure, weight, and lipids were relatively mixed. The GLP-1RA regimens had comparable safety profiles with regard to hypoglycemia and adverse events. Conclusion: Regimens of GLP-1RAs had differential glycemic control and cardiometabolic effectiveness. Policymaking and patient-centric clinical decisions should take into consideration the comparative effectiveness profiles.

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“…However, research in Jessica and Tina pointed out that further research is still needed to determine the effect of GLP-1 receptor agonists in overweight or obese patients without type 2 diabetes [ 11 , 12 ]. Studies have proven the efficacy and safety of PEX-168 in the treatment of patients with T2DM [ 13 , 14 ], but the effect of PEX-168 on simple obesity and on the regulation of chemerin and omentin expression has not been reported. This study therefore selected six indicators to evaluate the effect of PEX-168 according to prior research and the drug characteristics.…”

Section: Introductionmentioning

confidence: 99%

PEX-168 improves insulin resistance, inflammatory response and adipokines in simple obese mice: a mechanistic exploration

Guo

Zhu

et al. 2021

BMC Endocr Disord

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Background Polyethylene glycol loxenatide (PEX-168) is a new antidiabetic drug; as such, there are not yet any reports on its weight loss effect. Therefore, this trial was designed to investigate the effect of PEX-168 on simple obese mice. Methods Thirty healthy male C57BL/6 mice were randomly selected and divided into a control group (NC) and an obesity model group. The high-fat diet-induced simple obesity mice were divided into a model control group (HF) and three intervention groups. The intervention groups were injected with different doses of PEX-168 intraperitoneally once a week for 12 weeks (low (LD), medium (MD) and high (HD)). Fasting blood glucose (FBG), body weight and food intake were measured from 1 to 12 weeks after PEX-168 injection. The serum insulin (INS), C-reactive protein (CRP), chemerin and omentin levels were measured after 12 weeks. Results Compared with the HF group, the low dose of PEX-168 reduced the body weight of the mice in a short period of time (8 weeks), and the mice in the MD and HD groups showed a significant decrease in body weight (P < 0.05). The low dose of PEX-168 could effectively improve the blood glucose and homeostasis model assessment of insulin resistance (Homa-IR) of the mice (FBG P < 0.05 INS, Homa-IR P < 0.001), but there was no significant difference between different doses (P > 0.05). CRP levels in the MD and HD groups were significantly improved (P < 0.05). The levels of serum chemerin and omentin in the intervention groups were also significantly improved (P < 0.01), but there was no significant difference between the different doses (P > 0.05). Conclusions PEX-168 significantly reduced the body weight of simple obese mice and improved the insulin resistance. PEX-168 may regulate the expression of chemerin and omentin through its hypoglycaemic effect, and the weight-reducing effect of PEX-168 is unlikely to be the reason for the changes in both.

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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

Cited by 20 publications

References 34 publications

Polyethylene Glycol Loxenatide (PEX-168) Reduces Body Weight and Blood Glucose in Simple Obese Mice

Polyethylene Glycol Loxenatide (PEX-168) Reduces Body Weight and Blood Glucose in Simple Obese Mice

Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Network Meta-analysis

PEX-168 improves insulin resistance, inflammatory response and adipokines in simple obese mice: a mechanistic exploration

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