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Metabolic effects of glucagon-like peptide-1 receptor agonists The arGLP-1 s show a potent antihyperglycemic effect with decreases between 0.5% and 1.3% of HbA1c, which is greater in those with a long half-life56 with low risk of hypoglycemia, as has been shown in cardiovascular safety studies, where there were no differences in hypoglycemia rates versus placebo, except if associated with sulfonylureas or insulin.5764 The low risk of hypoglycemia has been observed even in patients with DKD.6567 who are more susceptible to this complication.16 It is also important to highlight the loss of weight and waist circumference with arGLP-1, mainly as a consequence of a reduction in body fat and not in lean mass, which is maintained during long-term follow-up.68 This weight loss is attributed to the slowing of gastric emptying which increases satiety, to the increase in resting energy consumption and its direct effects on appetite and satiety control centers in the CNS

Orforglipron isnt limited by peptide-like clearance

Chianelli M, Busetto L, Vettor R, Annibale B, Paoletta A, Papini E

These data were collected as part of an intervention study with two urine samplings at relatively high exposure (baseline) and two at lower exposure (intervention) to FB1