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The ADA guideline does state: "Combination of two GLP-1 receptor agonist-based therapies is not recommended due to lack of evidence and potential for additive adverse effects" [7]
Furthermore, it might have diminished the expression of urea cycle enzymes, possibly restored nitrogen balance, and, in theory, altered or improved nitrogen concentrations in different organs
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If tirzepatide remains ineffective despite optimization of all modifiable factors, alternative GLP-1 receptor agonists or other weight management medications may be considered
For example, a recent study examined animals that had a significant mutation in the growth hormone releasing hormone receptors (GHRHR) which led to decreased levels of circulating GH
Trials have shown meaningful weight loss, better sugar control, and fewer heart attacks, which is why semaglutide, liraglutide, dulaglutide, and tirzepatide have now been added to the WHO Model List of Essential Medicines
