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The challenge facing this strategy is that monotherapies often have varying pharmacokinetics and pharmacodynamics including half-life [69], meaning that the balance of target-receptor agonism may vary over time when using two different agents with varying profiles

Skin brightening focuses on improving overall radiance and addressing surface-level discolouration, whilst melanin reduction targets deeper pigmentation issues

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Antagonising glucagon receptors (GCGRs) with modified glucagon analogues, small molecules or antisense oligonucleotides has also been problematic because of the risk of hypoglycaemia and adverse effects on liver function, including steatosis and an increase in LDL-cholesterol

doi:10.1016/S0140-6736(23)01053-X PubMed: This trial evaluated retatrutide in 281 participants with type 2 diabetes, showing up to 16.94% weight loss and significant HbA1c reductions with favorable safety profile comparable to other GLP-1 based therapies

Notably, patients with obesity alone had higher discontinuation rates at 12 months (50.3%) compared to those with T2D alone (35.8%) and those with both conditions (34.2%)