Hormonal
Cotadutide, a dual GLP-1 and glucagon receptor agonist, significantly improves hepatic parameters (AST, ALT, FIB-4, NFS, PRO-C3) and lipid profiles (triglycerides) in patients with type 2 diabetes and obesity, with effects on liver enzymes appearing independent of weight loss.
For individuals with type 2 diabetes and obesity, cotadutide (a dual GLP-1/glucagon agonist) offers significant improvements in liver health markers (like AST, ALT, and fibrosis scores) and triglyceride levels, potentially beyond what standard GLP-1 drugs like liraglutide achieve. This benefit appears linked to the glucagon component of the drug. Treatment involves daily subcutaneous injections, starting at a low dose and titrating up, which helps manage initial gastrointestinal side effects like nausea. Patients should discuss this option with their healthcare provider, especially if they have concerns about liver health or lipid profiles.
Cotadutide 300 μg reduced PRO-C3 levels at 54 weeks versus placebo... while liraglutide 1.8 mg did not have an effect on PRO-C3 levels... These results suggest a potential effect of cotadutide on transaminase levels that was independent of weight loss, along with effects on plasma lipid levels that may be dependent on the glucagon-activity component of cotadutide.
Why this rating
Randomized, double-blind, placebo-controlled Phase 2b trial with a large sample size (n=834), though hepatic endpoints were assessed ad hoc.
Source
Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes: A 54-Week Randomized Phase 2b Study
Rajaa Nahra et al. · Diabetes Care · 2021
DOI 10.2337/dc20-2151
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
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