Protective effect of liraglutide on experimental testicular ischaemia reperfusion in rats

This study was performed to evaluate the effect of liraglutide on experimental testicular ischaemia reperfusion in rats in terms of biochemistry, histopathology and immunohistochemistry. A total of 28 male Wistar-Albino rats were divided randomly into 4 groups: control (7), sham (7), ischaemia-reperfusion (7) and ischaemia-reperfusion + liraglutide (7). Biochemically, Nitric Oxide, Malondialdehyde, Superoxide dismutase, Glutathione peroxidase and Catalase levels were measured in the testis. Apoptosis protease activating factor-1 and inducible nitric oxide synthase activity were evaluated immunohistochemically as well. Statistical analyses were made via the Kruskal–Wallis and Mann–Whitney U tests. In the reperfusion group, CAT and SOD values were increased (p > .05), NO and MDA values were decreased (p < .05) after administration of liraglutide. In addition, GPx values were significantly increased in ischaemia reperfusion + liraglutide administered group compared to reperfusion group (p < .05). Apaf-1 and iNOS activity were significantly decreased with the addition of liraglutide treatment to the ischaemia-reperfusion group (p < .05). First of all, we would like to say that liraglutide treatment is moderately preventive against I/R injury in testicular torsion. The anti-inflammatory, antioxidant and antiapoptotic properties of liraglutide are create a moderately protective effect as we show in this study.     

IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated Using Continuous Glucose Monitoring and a Standardized Meal Test

Objective:

IDegLira is a novel, fixed-ratio combination of the long-acting basal insulin, insulin degludec, and the long-acting glucagon-like peptide-1 analog liraglutide. We studied the effect of IDegLira versus its components on postprandial glucose (PPG) in type 2 diabetes.

Methods:

In this substudy, 260 (15.6%) of the original 1663 patients with inadequate glycemic control participating in a 26-week, open-label trial (DUAL I) were randomized 2:1:1 to once-daily IDegLira, insulin degludec or liraglutide. Continuous glucose monitoring (CGM) for 72 hours and a meal test were performed.

Results:

At week 26, IDegLira produced a significantly greater decrease from baseline in mean PPG increment (normalized iAUC_0-4h) than insulin degludec (estimated treatment difference [ETD] −12.79 mg/dl [95% CI: −21.08; −4.68], P = .0023) and a similar magnitude of decrease as liraglutide (ETD −1.62 mg/dl [95% CI: −10.09; 6.67], P = .70). CGM indicated a greater reduction in change from baseline in PPG increment (iAUC_0-4h) for IDegLira versus insulin degludec over all 3 main meals (ETD −6.13 mg/dl [95% CI: −10.27, −1.98], P = .0047) and similar reductions versus liraglutide (ETD −1.80 mg/dl [95% CI: −2.52, 5.95], P = .4122). Insulin secretion ratio and static index were greater for IDegLira versus insulin degludec (P = .048 and P = .006, respectively) and similar to liraglutide (P = .45 and P = .895, respectively).

Conclusions:

Once-daily IDegLira provides significantly better PPG control following a mixed meal test than insulin degludec. The improvement is at least partially explained by higher endogenous insulin secretion and improved beta cell function with IDegLira. The benefits of liraglutide on PPG control are maintained across all main meals in the combination.     

Glucagon‐like peptide‐1 analog,liraglutide, improves visceral sensation and gut permeability in rats

Background and Aim

A glucagon‐like peptide‐1 analog, liraglutide, has been reported to block inflammatory somatic pain. We hypothesized that liraglutide attenuates lipopolysaccharide (LPS)‐induced and repeated water avoidance stress (WAS)‐induced visceral hypersensitivity and tested the hypothesis in rats.

Methods

The threshold of the visceromotor response induced by colonic balloon distention was measured to assess visceral sensation. Colonic permeability was determined in vivo by quantifying the absorbed Evans blue spectrophotometrically, which was instilled in the proximal colon for 15 min. The interleukin‐6 level in colonic mucosa was also quantified using ELISA.

Results

Subcutaneously injected LPS (1 mg/kg) reduced the visceromotor response threshold after 3 h. Liraglutide (300 μg/kg subcutaneously) at 15 h and 30 min before injecting LPS eliminated LPS‐induced allodynia. It also blocked the allodynia induced by repeated water avoidance stress for 1 h for three consecutive days. Neither vagotomy nor naloxone altered the antinociceptive effect of liraglutide, but N^G‐nitro‐L‐arginine methyl ester, a nitric oxide synthesis inhibitor, blocked it. LPS increased colonic permeability and the interleukin‐6 level, and the analog significantly inhibited these responses.

Conclusions

This study suggests that liraglutide blocked LPS‐induced visceral allodynia, which may be a nitric oxide‐dependent response, and was probably mediated by inhibiting pro‐inflammatory cytokine production and attenuating the increased gut permeability. Because the LPS‐cytokine system is considered to contribute to altered visceral sensation in irritable bowel syndrome, these results indicate the possibility that liraglutide can be useful for treating this disease.     

Liraglutide Protects Neurite Outgrowth of Cortical Neurons Under Oxidative Stress though Activating the Wnt Pathway

Background

Neurogenesis including neurite outgrowth is important for brain plasticity under physiological conditions and in brain repair after injury. Liraglutide has been found to have neuroprotective action in the risk of central nervous system disease. However, the effect and the potential mechanism of liraglutide-induced neurite outgrowth in primary cortical neurons under oxidative stress remain poorly documented.

Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials

Tirzepatide is a new glucagon-like peptide-1 receptor agonist (GLP-1RA) that has shown promising results for weight loss. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of GLP-1RAs for obesity management. Embase and MEDLINE were searched looking for randomized clinical trials (RCTs) that evaluated the efficacy of GLP-1RAs for weight loss in patients without diabetes. The main efficacy outcomes evaluated were the mean change in actual and percentage weight loss and the proportion of patients with weight loss of ≥5%–20%. Main safety outcomes evaluated include nausea, vomiting, diarrhea, constipation, loss of appetite, pancreatitis, gallbladder-related disorders, and withdrawal due to adverse events. Seven RCTs with more than 12,300 patients were analyzed, including patients with body mass index (BMI) ≥ 30 kg/m², or BMI ≥ 27 kg/m² with comorbidities. Weekly tirzepatide 10 and 15 mg resulted in more weight loss than weekly semaglutide 2.4 mg, daily semaglutide 0.4 mg, or liraglutide 3 mg. Tirzepatide and weekly semaglutide demonstrated comparable results but with significantly higher odds of achieving ≥5%–20% weight loss compared with liraglutide. GLP-1RAs triggered more gastrointestinal adverse events than placebo, with no in-between difference. Although all GLP-1RAs lead to significant weight reduction, tirzepatide was associated with better efficacy outcomes while having a comparable safety profile.     

The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in patients with type 2 diabetes (TROPHIES): Final, 24-month analysis of time to first significant treatment change,treatment persistence and clinical outcomes

Aims

To present the final results of the TROPHIES study (The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in patients with type 2 diabetes).

Materials and Methods

The prospective, real-world TROPHIES study included patients with type 2 diabetes initiating their first injectable glucose-lowering medication (GLM), dulaglutide or liraglutide, in France, Germany and Italy. The primary endpoint was the time spent on dulaglutide or liraglutide until a significant treatment change over 24 months. Other endpoints measured persistence with treatment, clinical outcomes (glycated haemoglobin [HbA1c] and weight) and treatment patterns. Kaplan-Meier estimates of time to first significant treatment change and persistence with treatment were generated. Propensity-score-based inverse probability of treatment weighting (IPTW) was used to adjust for baseline imbalances in the comparison between cohorts.

Results

The 286 of 1014 patients (28.2%) in the dulaglutide cohort and 448 of 991 patients (45.2%) in the liraglutide cohort had a significant treatment change over 24 months. By IPTW analysis, dulaglutide-initiating patients were less likely to have a significant treatment change (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.46-0.63) and more likely to be persistent with treatment (HR 0.69, 95% CI 0.56-0.86) over 24 months than liraglutide-initiating patients. Dulaglutide and liraglutide yielded similar HbA1c (−11.80 mmol/mol [1.08%] and −11.91 mmol/mol [1.09%]) and weight (−3.5 kg and −3.3 kg) reductions from baseline to 24 months. Few changes in patterns of treatment with other GLMs were observed in the two cohorts.

Conclusions

Dulaglutide-initiating patients had a longer time spent without any significant treatment change and higher persistence than those initiating liraglutide. Treatment with either glucagon-like peptide-1 receptor agonist yielded similar and clinically meaningful reductions in HbA1c and body weight.