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A total of 3050% of patients taking this class of drug at clinically licensed doses experience nausea 15

Even a quarterly injection in early development

A 2023 review in the Journal of Clinical Endocrinology & Metabolism highlighted that GLP-1s can delay gastric emptying significantly, especially at higher doses or early in treatment.44 Another study found that just over 5% of patients experience gastroparesis and it was more likely when using liraglutide or dulaglutide when compared with semaglutide.45 A 2024 cross-sectional analysis in Pharmaceuticals examined the GI side effects of semaglutide, dulaglutide, liraglutide, and exenatide in over 10,000 adults with T2DM or obesity from the National Institutes of Health All of Us cohort.45 They found that abdominal pain was the most frequently reported GI issue (57.6%), followed by constipation, diarrhea, nausea/vomiting, GI bleeding, gastroparesis, and pancreatitis

This Gs-biased profile may contribute to sustained receptor signaling with less desensitization, though the clinical implications of signaling bias in GLP-1 therapeutics remain an area of active investigation

Patients with T2D not adequately controlled on therapy with metformin and insulin glargine as baseline therapy received either tirzepatide at the doses used in the SURPASS trials or placebo during the 40-week study setting