GIP/GLP-1 Dual Agonists: Special-Populations Prescribing Summary

Which drug is a dual agonist?

Tirzepatide is the GIP/GLP-1 dual agonist among the FDA-approved GLP-1-class products, sold as Mounjaro and Zepbound [1][2]. The other products in the class are single GLP-1 receptor agonists [3][4].

Boxed warning and contraindications

Mounjaro and Zepbound carry a boxed warning about thyroid C-cell tumors observed in rodents; whether this risk applies to humans is unknown [1][2]. The wording is not uniform across the group: Byetta carries no boxed warning, and the Foundayo warning reads differently because orforglipron is not pharmacologically active in rodents [4][5].

The tirzepatide contraindications include a personal or family history of medullary thyroid carcinoma or MEN 2 [1][2]. The GLP-1 labels also contraindicate a prior serious hypersensitivity reaction to the drug or its ingredients [3][4].

Pregnancy and contraception

The weight-management labels state that weight loss offers no benefit in pregnancy, and they advise stopping the drug when pregnancy is recognized [3][4][1]. The Wegovy and Foundayo labels also say the drug may cause fetal harm [3][4].

The tirzepatide label gives specific contraceptive advice: people using oral hormonal contraceptives are advised to switch to a non-oral method or add a barrier method for 4 weeks after starting and for 4 weeks after each dose increase [1].

Dehydration, kidney injury and GI tolerability

Acute kidney injury due to volume depletion is a warning on the Wegovy and Foundayo labels. The Foundayo label says the majority of reported events occurred in patients whose nausea, vomiting or diarrhea led to dehydration, and both labels say to monitor renal function in patients reporting reactions that could lead to volume depletion [3][4].

Gastrointestinal effects are the common problem and are worst during escalation. In the Zepbound weight-management trials at 15 mg, nausea occurred in 28%, vomiting in 13%, diarrhea in 23% and constipation in 11%, against 8%, 2%, 8% and 5% with placebo [1].

Combining with another GLP-1 drug

The Wegovy, Saxenda, Zepbound and Foundayo labels state that use with another GLP-1 receptor agonist is not recommended [3][6][1][4].