Semaglutide approval drove a surge in GLP-1 poison center exposures

Semaglutide's success reshaped GLP-1 prescribing patterns

GLP-1 RAs have been prescribed for type 2 diabetes (T2D) since 2005, beginning with exenatide. These agents mimic endogenous GLP-1, thereby enhancing insulin secretion, suppressing glucagon secretion, delaying gastric emptying, and reducing food intake. Exenatide and liraglutide demonstrated glycemic and weight loss benefits in both diabetic and non-diabetic populations, leading to regulatory approval of liraglutide for chronic weight management in obesity.

Semaglutide, a once-weekly injection, produced greater reductions in hemoglobin A1c (HbA1c) and body weight than comparators. Clinical trials showed a mean weight loss of 12.4% with 2.4 mg of semaglutide, supporting its approval for the treatment of obesity. Its efficacy and convenient dosing have driven a marked increase in GLP-1 RA prescriptions, especially from 2020 to 2024, among patients with obesity or diabetes.

GLP-1 agonists promote weight loss by delaying gastric emptying, reducing appetite, and increasing satiety, thereby lowering caloric intake, decreasing body fat, and improving insulin sensitivity.

Delayed gastric emptying can cause nausea and vomiting, sometimes leading to dehydration and electrolyte disturbances. Links between GLP-1 RAs and pancreatitis or pancreatic cancer remain inconclusive. Hypoglycemia risk is increased in patients using insulin or sulfonylureas, but may vary by agent rather than represent a class effect.

Despite widespread adoption and escalating prescribing of GLP-1 receptor agonists for weight loss, there is limited understanding of the national impact of acute exposures, particularly in the context of their use for obesity following regulatory approval. Existing studies have not adequately addressed whether the shift in prescribing patterns has altered the frequency or characteristics of toxicity events.

This lack of robust, population-level data represents a critical research gap, underscoring the need to systematically assess trends in GLP-1 RA exposures and associated outcomes at a national level.

Poison center data tracked GLP-1 exposure trends

A retrospective analysis of human exposures to GLP-1 RAs reported to the National Poison Data System (NPDS) from January 1, 2012, to December 31, 2023, was conducted. The NPDS, maintained by America’s Poison Centers, collects de-identified case records from all U.S. poison centers.

The current study included exposures of GLP-1 RAs, including exenatide, liraglutide, dulaglutide, albiglutide, semaglutide, tirzepatide, or unspecified, as the primary substance. Animal exposures and information-only calls were excluded. Exposures on or after July 1, 2021, following FDA approval of once-weekly semaglutide for weight loss, were categorized as post-approval to align with the calendar quarter and expected clinical uptake.

NPDS clinical effects are coded as binary indicators (“related,” “not related,” or “unknown if related”) and analyzed by period. For the primary analysis, “unknown if related” symptoms were grouped with “related” to maximize sensitivity, and a sensitivity analysis compared the proportions of “unknown” pre- and post-approval.

Semaglutide drove a sharp rise in reported exposures

A total of 10,033 GLP-1 RA exposures were reported, with cases rising sharply after July 1, 2021. Reporting volume more than doubled after approval, marking a clear shift in exposure trends. Time-series analysis confirmed this significant increase, with semaglutide-related calls increasing by an additional nearly 10% per quarter after the 2021 approval.

After July 2021, semaglutide replaced liraglutide and dulaglutide as the most common exposure, making up over 60% of cases. Patients were younger and more likely to be female. While most exposures occurred at home, there was a distinct rise in acute exposures, consistent with greater new use.

Most GLP-1 RA exposures resulted from accidental therapeutic errors, though this declined slightly after July 2021. Adverse reactions became more frequent, while intentional or non-therapeutic cases stayed rare. After approval, more errors involved the wrong drug or timing, but fewer involved the wrong dose.

After July 2021, more exposures were reported from health care facilities, and fewer calls originated from homes. On-site management decreased, with more patients already in, en route to, or referred to health care facilities. Medical outcomes shifted, with fewer “no effect” cases and more minor, moderate, and prolonged symptoms. Gastrointestinal and neurologic symptoms, especially nausea, vomiting, and abdominal pain, became more frequent, while hypoglycemia reports declined.

Sensitivity analysis showed improved certainty in symptom attribution after July 2021, with fewer cases coded as “unknown” for major gastrointestinal effects. Coding specificity remained stable or improved, except for the broad “other” category.

Use of recommended therapies increased after July 2021, with antiemetic and intravenous fluid recommendations rising sharply, reflecting greater involvement by health care facilities. Quarterly call volume rose sharply after mid-2021, as confirmed by regression analysis. The Poisson model provided the best fit, highlighting a significant change in reporting trends after FDA approval.

Poison center data highlight evolving GLP-1 safety trends

Since the 2021 approval of semaglutide for weight-loss indications, GLP-1 RA exposures have risen markedly. While most exposures resulted in mild, self-limited gastrointestinal symptoms. There was also a notable increase in healthcare facility referrals, from 23.0% before approval to 33.5% afterward, highlighting that even exposures considered clinically non-severe can drive substantial healthcare utilization.

Because poison center reports are voluntary and influenced by prescribing trends, media attention, and healthcare-seeking behavior, the findings cannot determine the true incidence of GLP-1 RA toxicity or establish causality. The current study findings underscore the utility of poison center data for near-real-time surveillance of post-marketing drug trends. 

The study also found no documented cases of pancreatitis, although the authors note that poison center records do not routinely capture laboratory results, limiting the ability to confirm or exclude this diagnosis.

 By prioritizing patient education and improving counseling for patients and prescribers on dose titration, product switching, and management of expected gastrointestinal effects, alongside clear prescribing guidance and poison center recommendations, the healthcare community can help ensure that the benefits of GLP-1 RAs are maximized while minimizing adverse outcomes.

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