Seyyed Mostafa Arabi
1,2 
, Iman Rahnama
3, Mahsa Malek Ahmadi
4,5, Mohtaram Hashemi
6, Mohammad Mahdi Marvi
7, Sana Mahdian
8, Leila Sadat Bahrami
1, Amirhossein Sahebkar
9,10,11,12* 1 Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
2 Healthy Ageing Research Centre, Neyshabur University of Medical Sciences, Neyshabur, Iran
3 Binaloud Institute of Higher Education, Mashhad, Iran.
4 Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
5 Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
6 Students Research Committee, Semnan University of Medical Sciences, Semnan, Iran.
7 DVM student in the Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
8 Students Research Committee, Neyshabur University of Medical Sciences, Neyshabur, Iran.
9 Applied Biomedical Research Center, Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
10 Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India
11 Center for innovation and inclusive research, Sharda University, Greater Noida, Uttar Pradesh, India
12 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract
Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose transporter 2 inhibitors (SGLT2i) are a relatively new class of drugs used to improve cardiometabolic risk factors. The aim of this meta-analysis was to systematically evaluate the effects of combination therapy of GLP-1RAs and SGLT2i on cardiometabolic markers in adults. Methods: MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science were thoroughly searched using relevant keywords and MeSH-terms from inception until September 2023 for randomized trials addressing the effects of GLP-1Ras and SGLT2 inhibitors on cardiometabolic markers. Only English-language randomized clinical trials involving adults (≥18 years) treated with GLP-1Ras and SGLT2is, with cardiometabolic outcomes and placebo controls, were included. A random-effects meta-analysis was performed to assess changes in glucose hemostasis, lipid profile, blood pressure, and anthropometric parameters. Subgroup analyses were conducted to assess the impact of the study on health status, intervention types, concurrent diets, study design and blinding, participant age, and treatment duration. PROSPERO registration: CRD42023471047. Results: Four studies (5 arms) involving 249 patients were analyzed, which showed that treatment with GLP-1RA and SGLT2 inhibitors reduced fasting plasma glucose (FPG) by an average of -11.8 mg/dL (95% confidence interval [CI]: -16.7 to -6.9; p<0.001), systolic blood pressure (SBP) by an average of -7.4 mmHg (95% CI: -10.6 to -4.1; p<0.001), body weight by an average of -3.8 kg (95% CI: -5.2 to -2.4; p<0.001), and waist circumference by an average of -3.5 cm (95% CI: -5.8 to -1.1; p=0.003). Conclusion: GLP-1RA and SGLT2 inhibitor therapy improve cardiometabolic outcomes by lowering FPG, SBP, BW, and WC, which may alleviate downstream complications. Further research is needed to characterize the long-term effects on cardiometabolic markers.