Impact of Cotadutide drug on patients with type 2 diabetes mellitus: a systematic review and meta-analysis

Abstract

Background The food and drug administration approved many drugs to treat diabetes mellitus, but those drugs do not have a noticeable effect on weight management. Recently, glucagon-like peptide 1 agonist known as Cotadutide serve as a potent drug in treating type 2 diabetes by reducing blood glucose levels and body weight indices. This study aimed to explore the safety and efficacy of Cotadutide as a treatment for type 2 diabetes individuals. Methods A comprehensive literature search was done on different databases, including PubMed, Scopus, Web of Science, and Cochrane Library to capture all relevant articles using an established search strategy. The inclusion criteria were randomized controlled trials that assessed the safety and efficacy of Cotadutide versus placebo or any anti-diabetes drugs in patients with type 2 diabetes mellitus and a BMI between 22 kg/m2 and 40 kg/m2. We conducted the analysis using Revman software version 5.4. Results We found 663 relevant articles. From which nine studies were included and subjected to qualitative analysis and eight for quantitative analysis. The pooled effect showed that Cotadutide was better than placebo in reducing body weight (kg) (Mean difference (MD) = 3.31, p < 0.00001), glycated hemoglobin (HbA1c) (MD = 0.68, p > 0.00001), glucose area under the plasma concentration curve (AUC [0-4 h]) (MD = 30.15, p < 0.00001), and fasting plasma glucose over time (mg/dl) (MD = 31.31, p < 0.00001). Conclusion Cotadutide is safe and effective in reducing plasma glucose levels, HbA1c and body weight in individuals with type 2 diabetes. Trial registration The study protocol was registered on PROSPERO (CRD: CRD42021257670).

GLP-1R Signaling and Functional Molecules in Incretin Therapy

“…Although glucagon and GLP-1 have distinct effects on glucose levels, their effects on food intake may be additive [ 88 ], leading to more significant body-weight reduction. Several OXM derivatives are under clinical trials, for example, cotadutide, a once-daily GCGR/GLP-1R dual agonist, has shown promising impacts on glycemic control, body weight, and liver fat reduction [ 89 ].…”

Type 2 Diabetes (T2DM) and Parkinson’s Disease (PD): a Mechanistic Approach

“…In a Bayesian network meta-analysis study, the effective role of Chinese tradition medicine against T2DM was deliberated comparing with western medicines [ 152 ]. The cotadutide drug has been a potent drug in treating T2DM which has been effective in decreasing glucose levels, haemoglobin A, and body weight [ 156 ]. The Chinese medicine Astragali Radix-Coptis Rhizoma and Allium sativum L. was used to treat T2DM were its mechanistic action using network pharmacology was explained in a study [ 171 , 172 ].…”

Why do some glucose‐lowering agents improve non‐alcoholic fatty liver disease whereas others do not? A narrative review in search of a unifying hypothesis

“…Another dual agonist consisting of GLP‐1 and glucagon (GCG) receptor agonist, named cotadutide, yet not approved by the FDA, has been shown to reverse hepatic steatosis in murine models and there are currently various ongoing trials to evaluate its efficacy on the metabolic consequences of diabetes 82 . The weight‐lowering effects of cotadutide appear to be less impressive than those of tirzepatide and some GLP‐1 RA 80 , endorsing the hypothesis that effects on NAFLD are not exclusively related to weight loss.…”