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On the latter, studies conducted using site-specific brain micro-injections and single-photon emission computed tomography documented a novel regulatory role of the hypothalamic supramammillary nucleus in the regulation of food intake and reward, posing this brain area as one of the main targets of the GLP1/E conjugate, along with the lateral hypothalamus and the nucleus of the solitary tract, whose activation may be responsible for the anorectic, weight-lowering and reward reducing effects of this multi-agonist 51

Due to overwhelming demand, both semaglutide and tirzepatide have experienced periodic shortages of certain dosage strengths

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But it does suggest that the theoretical rationale for combining these compounds is weak even at the mechanistic level