Tolerability

Tolerability

Tolerability is how well patients can cope with a drug’s side effects while staying on treatment. It is a key part of a drug’s profile: even a very effective drug is of little use if people cannot tolerate it long enough to benefit. Tolerability is usually judged by how often side effects occur and how severe they are, how many people stop treatment, and how often doses need changing.

With GLP-1 receptor agonist-based drugs, tolerability is closely tied to gastrointestinal side effects such as nausea, vomiting and diarrhea. These come directly from GLP-1 receptor activation in the gut and brainstem and tend to be worst while the dose is being raised. Increasing the dose gradually is the main way to improve tolerability, giving the body several weeks to adjust to rising drug levels.

In retatrutide trials, gastrointestinal side effects were the most common, as expected from the drug’s GLP-1 component. In the Phase 2 obesity trial, about 6-16% of participants in the active treatment groups stopped because of side effects, depending on the dose. These rates are broadly similar to other incretin-based drugs, which suggests that adding GIP and glucagon receptor activity does not make the drug much harder to tolerate.