Triple Agonists (GLP-1/GIP/Glucagon) Drug-Drug Interaction Table

What interactions are documented for approved GLP-1 drugs?

The Wegovy label states that semaglutide delays gastric emptying and has the potential to affect absorption of oral medicines, and advises considering increased clinical or laboratory monitoring for oral drugs with a narrow therapeutic index or that require clinical monitoring [3]. The Zepbound and Foundayo labels describe the same effect [5][4].

Two label details matter. In clinical pharmacology trials with semaglutide 1 mg injection, semaglutide did not affect absorption of orally administered medications [3]. With the semaglutide tablet, levothyroxine exposure increased 33% (90% CI 1.25 to 1.42) [3].

Insulin and sulfonylureas

The Wegovy label says hypoglycemia risk increases when it is used with insulin or an insulin secretagogue, and advises considering a lower dose of the insulin or secretagogue when starting [3]. The Foundayo label carries the same instruction [4]. In the orforglipron type 2 diabetes trial, hypoglycemia (plasma glucose under 54 mg/dL) was reported in 7% of patients taking a sulfonylurea versus 0.5% of those not taking one [4].

Oral contraceptives

Advice differs by product. The Zepbound label advises switching to a non-oral method or adding a barrier method for 4 weeks after starting and after each dose increase [5]. The Foundayo label advises the same for 30 days after initiation and after each dose escalation [4]. Semaglutide labels carry no such advice, and a tablet interaction study found no clinically significant change in ethinyl estradiol or levonorgestrel [3].

Product-specific rules

The Foundayo label caps the dose at 9 mg with a strong CYP3A4 inhibitor, says to avoid strong CYP3A4 inducers, and limits simvastatin to 20 mg daily because simvastatin acid exposure doubled [4]. These instructions apply to Foundayo. Whether they apply to retatrutide has not been established [4][1].

What the retatrutide trial reported

A phase 2 trial enrolled 338 adults with a BMI of 30 or higher, or 27 to under 30 plus a weight-related condition, and gave weekly subcutaneous retatrutide or placebo for 48 weeks [1]. The trial's end points were weight change and safety [1]. The most common adverse events were gastrointestinal, dose-related, and mostly mild to moderate [1].