Study of 60,000 Patients Finds 58% Restart GLP-1 Drugs Within 2 Years

Q: Can genetic testing soon predict who will benefit from GLP-1s, personalizing a path to treatment success?

Yes—but not yet as a routine clinical tool. The strongest evidence so far suggests genetic testing could soon help predict both who is more likely to lose weight on GLP-1 drugs and who is more likely to develop side effects that often drive people to stop treatment. A large study of nearly 28,000 GLP-1 users identified a variant in the GLP1R gene linked to greater weight-loss response, and variants in GLP1R and GIPR linked to nausea and vomiting. The GIPR signal appeared especially relevant for tirzepatide, which targets both GLP-1 and GIP pathways. That matters because the new ENDO 2026 data show GLP-1 use is often “start-and-stop”: 40% of patients discontinued within a year, though many later restarted. If clinicians could identify in advance who is likely to respond well, or who may need slower dose escalation because of side effects, treatment could become more durable and better tailored. Still, experts caution that genetics is only part of the picture. The known genetic effects are real but modest, and response is also shaped by drug choice, dose, diabetes status, age, sex, ancestry, baseline BMI, cost, insurance coverage, and access. In practice, those non-genetic barriers remain major reasons patients discontinue therapy. So the field is moving toward precision prescribing, but it is not yet at the point where a genetic test alone can reliably determine success. In the near term, genetics is more likely to complement clinical factors than replace them.

3 articles · Updated · The Pharmaceutical Journal · Jun 17

Insurance-claims data from 60,000 U.S. adults with type 2 diabetes showed GLP-1 use was often intermittent: 42% of those who stopped restarted within one year and 58% within two years.
About 40% discontinued within the first year and nearly 60% by two years, with discontinuation defined as a gap of more than 60 days between prescriptions.
Tirzepatide users were 41% less likely to discontinue than liraglutide users, while Semaglutide users were 28% less likely to stop than patients on older drugs.
Researchers said the pattern suggests these medicines are not usually abandoned permanently, but stop-and-start use could weaken benefits such as protection against heart attacks, kidney disease progression and other complications.