Evaluating the safety and efficacy of the leukotriene receptor antagonist montelukast as adjuvant therapy in obese patients with type 2 diabetes mellitus: A double-blind, randomized, placebo-controlled trial

Eman El-Khateeb; Eman I El-Berri; Esraa M Mosalam; Mohamed Z Nooh; Shimaa Abdelsattar; Amira M Alghamdi; Sarah Alrubia; Mahmoud S Abdallah

doi:10.3389/fphar.2023.1153653

Evaluating the safety and efficacy of the leukotriene receptor antagonist montelukast as adjuvant therapy in obese patients with type 2 diabetes mellitus: A double-blind, randomized, placebo-controlled trial

Front Pharmacol. 2023 Apr 11:14:1153653. doi: 10.3389/fphar.2023.1153653. eCollection 2023.

Authors

Eman El-Khateeb^{1

2}, Eman I El-Berri¹, Esraa M Mosalam³, Mohamed Z Nooh⁴, Shimaa Abdelsattar⁵, Amira M Alghamdi⁶, Sarah Alrubia⁷, Mahmoud S Abdallah⁸

Affiliations

¹ Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta, Al-Gharbia, Egypt.
² Certara UK Limited (Simcyp Division), Sheffield, United Kingdom.
³ Department of Biochemistry, Faculty of Pharmacy, Menoufia University, Shebin ElKoum, Egypt.
⁴ Department of Internal Medicine, Faculty of Medicine, Menoufia University, Shebin ElKoum, Egypt.
⁵ Department of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoufia University, Shebin ElKoum, Egypt.
⁶ Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
⁷ Pharmaceutical Chemistry Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
⁸ Department of Clinical Pharmacy, Faculty of Pharmacy, University of Sadat City, Sadat City, Menoufia, Egypt.

Abstract

Background: Type 2 diabetes mellitus (T2DM) is common with obesity. Metformin is a first-line therapy for this condition. However, it has only a minor impact on weight loss in some patients. Aim: This study aimed to evaluate the effectiveness, tolerability, and safety of combining montelukast therapy with metformin in obese diabetic patients. Methods: One hundred obese diabetic adult patients were recruited and randomized into two equal groups. Group 1 received placebo plus metformin 2 g/d, and Group 2 received 2 g/d metformin plus 10 mg/d montelukast. Demographic, anthropometric measurements (e.g., body weight, body mass index [BMI], and visceral adiposity index), lipid profile, diabetes control measures (fasting blood glucose, glycated hemoglobin [HbA1c], and homeostatic model assessment for insulin resistance [HOMA-IR]), adiponectin, and inflammatory markers (e.g., TNF-α, IL-6, and leukotriene B4) were assessed and reported for each group at baseline and after 12 weeks of treatment. Results: Both interventions significantly reduced all the measured parameters, except for adiponectin and HDL-C, levels of which increased compared to baseline data (p < 0.001). The montelukast group significantly improved in all parameters compared to the placebo group (ANCOVA test p < 0.001). The percentage changes in BMI, HbA1c, HOMA-IR, and inflammatory markers were 5%, 9%, 41%, and 5%-30%, respectively, in the placebo group compared to 8%, 16%, 58%, and 50%-70%, respectively, in the montelukast group. Conclusion: Montelukast adjuvant therapy was superior to metformin-only therapy in diabetes control and weight loss, most likely due to its increased insulin sensitivity and anti-inflammatory properties. The combination was tolerable and safe throughout the study duration. Clinical Trial Registration: [Clinicaltrial.gov], identifier [NCT04075110].

Keywords: T2DM; diabetes; leukotriene receptor antagonist; metformin; montelukast; obesity.

Associated data

ClinicalTrials.gov/NCT04075110