GLP-1 Discontinuation Cuts Chances of Meeting Weight Loss, Glycemic Goals in T2D

A real-world analysis of more than 18,000 patients with type 2 diabetes (T2D) found nearly half discontinued glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy within 1 year, with discontinuation independently associated with substantially lower odds of achieving guideline-recommended weight loss and glycemic targets.¹

The findings, presented at the American Diabetes Association (ADA) 2026 Scientific Sessions, quantify what many clinicians observe in practice: GLP-1 RA persistence is a major determinant of whether patients realize the metabolic benefits these agents can provide. Current guidelines recognize ≥ 5% weight reduction as clinically meaningful and an HbA1c < 7% as a standard glycemic target in T2D.

The analysis drew from the Market Clarity claims-EHR linked database, identifying 18,187 adults with T2D, BMI of ≥ 25 kg/m², and baseline HbA1c of ≥ 7% who initiated a GLP-1 RA between January 2021, and June 2024.¹ All patients had BMI and HbA1c measurements within 90 days before initiation and a follow-up measure at 365 ± 90 days after initiation.

Discontinuation was defined as a gap of ≥ 60 days without any GLP-1 supply. Multivariable regression adjusted for clinical and demographic characteristics estimated the association between discontinuation and achievement of BMI and HbA1c goals over 1 year.

Over the follow-up period, 8551 patients (47.0%) discontinued GLP-1 RA therapy.¹ Among those who discontinued versus those who persisted, 33.0% versus 55.0% achieved ≥ 5% BMI reduction, 12.1% versus 26.9% achieved ≥ 10% BMI reduction, and 31.2% versus 60.9% reached an HbA1c < 7%, respectively.

After multivariable adjustment, patients who discontinued were 41% less likely to achieve ≥ 5% BMI reduction (risk ratio [RR], 0.59; 95% CI, 0.57-0.62), 56% less likely to achieve ≥ 10% BMI reduction (RR, 0.44; 95% CI, 0.41-0.47), and 47% less likely to achieve an HbA1c < 7% (RR, 0.53; 95% CI, 0.51-0.55).¹

The analysis also identified a gradient effect among those who did not discontinue. Approximately 10% of nominally persistent patients had prescription fill rates at or below 80%, reflecting suboptimal adherence without meeting the 60-day gap threshold for discontinuation. Even within the persistence group, less consistent use was associated with attenuated outcomes compared with patients filling prescriptions regularly, reinforcing dose consistency as a meaningful variable alongside persistence itself.

Vivian Fonseca, MD, Tullis Tulane Alumni Chair in Diabetes at Tulane University School of Medicine and an investigator on the analysis, told HCPLive the discontinuation rates observed are consistent with what he encounters in clinical practice. He cited tolerability, cost, injection burden, and patient expectations as primary drivers. He noted the pattern differs from other chronic disease contexts: patients initiating GLP-1 RAs for weight loss often do not anticipate lifelong therapy, unlike those starting antihypertensives or statins.

"GLP-1 is very good, not just for weight, but also for treating diabetes," Fonseca said. "If they stop, [glucose control] will deteriorate unless they're moving over to some other medication."

Fonseca emphasized expectation-setting as a clinical tool for reducing early discontinuation. He noted a subset of patients achieve little to no weight loss on GLP-1 RAs and may require alternative approaches, making early identification of non-responders a practical priority. He also highlighted the need for studies on weight maintenance strategies, suggesting aggressive titration to a maximum tolerated dose may not be necessary indefinitely and more nuanced long-term regimens could support sustained adherence.

Editors’ note: Fonseca reports relevant disclosures with Novo Nordisk, Regeneron, Abbott, Corcept, Eli Lilly, and others.

References

1. Fonseca V, Girguis M, Donsmark M, et al. Impact of GLP-1–based treatment discontinuation on weight loss and glycemic goals among patients with type 2 diabetes: quantifying an opportunity to improve treatment benefits. Presented at: American Diabetes Association 2026 Scientific Sessions; June 2026.

2. American Diabetes Association. Standards of care in diabetes. Diabetes Care. 2026. https://professional.diabetes.org/standards-of-care