Selective GIP receptor agonist produces weight loss without nausea in Phase 1

Eli Lilly researchers reported early results at the American Diabetes Association's 2023 meeting for LY3537021, an experimental drug that acts only on the GIP hormone receptor. In a small, early-stage study, people who took the drug once a week for four weeks lost weight, and none of them reported nausea or vomiting ^[1].

The study, presented June 20, 2023, tested the drug in two stages ^[1]. In the first stage, researchers gave single doses to 39 healthy adults, averaging 43.5 years old and 74.4 kg (about 164 pounds), and to 6 people with type 2 diabetes, averaging 58.5 years old and 75.1 kg (about 166 pounds) ^[1]. The drug stayed in the body a long time, with a half-life of roughly 11 to 14 days, and it behaved similarly in people with and without diabetes ^[1].

In the second stage, 18 healthy adults and 18 people with type 2 diabetes received either the drug or a placebo once a week for four weeks ^[1]. By day 57, healthy participants who took the drug lost between 1.1 and 2.2 kg (about 2.4 to 4.9 pounds), on average, compared with 0.4 kg for those on placebo ^[1]. People with type 2 diabetes who took the drug lost between 1.9 and 3.1 kg (about 4.2 to 6.8 pounds), compared with 0.4 kg for those on placebo ^[1]. These are described as "numerically greater" losses rather than results proven with formal statistical testing ^[1].

Side effects were mild and few. Some participants reported decreased appetite, abdominal pain, or diarrhea, but researchers recorded no nausea, no vomiting, no serious adverse events, and no low blood sugar episodes ^[1]. The drug also did not slow stomach emptying, a mechanism thought to contribute to nausea with other incretin drugs ^[1]. Lilly's authors wrote that the findings suggest GIP receptor activity on its own can help drive weight loss, adding to the case that GIP contributes something distinct from GLP-1 in drugs like tirzepatide (Mounjaro, Zepbound), which activates both GIP and GLP-1 receptors ^[1].

The study was small, short, and funded by Lilly, whose employees make up most of the author list ^[1]. The research abstract itself notes that GIP's role in weight loss has been unclear, in part because some approaches that block GIP alongside GLP-1 activation have also shown weight loss benefits, meaning scientists have not settled on exactly how GIP works in weight regulation ^[1].

Why it matters for patients

Many people stop GLP-1 medicines such as semaglutide (Ozempic, Wegovy, Rybelsus) or reduce their dose because of nausea, vomiting, or other stomach-related side effects. If a GIP-only drug can produce weight loss without those symptoms, it could eventually offer another option for people who cannot tolerate current drugs. This early study is not proof that such a drug works as well or is as safe as approved options — it involved a small number of people over just four weeks of dosing ^[1]. It says nothing about long-term weight loss, long-term safety, or how the drug would perform in a larger, more diverse population.

What happens next

The source does not describe specific next steps, dates, or larger trials for LY3537021 beyond this early-phase data presented at the ADA meeting on June 20, 2023 ^[1]. Whether Lilly moves this compound into larger studies, and how it might compare with existing GLP-1 and dual GIP/GLP-1 medicines, is not yet known from this report.