Safety Reassurance for Major Class of Diabetes Drugs

GLP-1 receptor agonists weren't tied to increased risk for incident breast cancer, new research indicated.

In a systematic review and meta-analysis of 52 randomized, controlled trials, rates of breast cancer were nearly identical in adults with obesity or diabetes treated with such agents versus other drug classes (relative risk 0.98, 95% CI 0.76-1.26), reported Giovana Fagundes Piccoli, MD, of the Hospital de Clínicas de Porto Alegre in Brazil.

Among the entire cohort, there were 130 cases of incident breast cancer among 48,267 patients treated with a GLP-1 receptor agonist versus 107 cases out of 40,755 controls, Piccoli explained at the Endocrine Society's virtual ENDO 2021 meeting.

Control participants included patients receiving either placebo or active treatment with a non-GLP-1 receptor agonist.

There was also no difference in risk of benign breast neoplasms for patients on GLP-1 receptor agonists versus other drug types (RR 0.99, 95% CI 0.48 to 2.01).

And there was no difference among individual GLP-1 receptor agonists. To assess this, the researchers compared each of the four major drugs in the class -- liraglutide (Saxenda, Victoza), dulaglutide (Trulicity), semaglutide (Ozempic, Rybelsus), and albiglutide (Tanzeum) -- with exendin-4 mimetic agents including exenatide (Byetta, Bydureon) and lixisenatide (Adlyxin).

Comparing trials with an open-label design versus double-blinded trials yielded no difference in incident breast cancer risk.

Piccoli explained her group wanted to delve deeper into this issue after the 2015 SCALE Obesity and Prediabetes trial, which found more breast neoplasms in patients receiving liraglutide than with placebo (4.36 vs 1.80 per 1,000 person years). Most such neoplasms in that study developed within the first year of GLP-1 receptor agonist treated and were more common in participants who lost more weight on the agent.

"I think that the results of our meta-analysis adds more security and safety information about this treatment," said Piccoli during a press conference. "Patients, doctors, and other health professionals can be more secure of the safety of these drugs."

For this analysis, her group searched MEDLINE, Embase, Web of Science, and CENTRAL databases to include randomized trials assessing GLP-1 receptor agonists in adults with overweight, obesity, prediabetes, or type 2 diabetes that also reported breast cancer or benign breast neoplasm incidence.

In the meta-analysis, the ages of the participants ranged from 45 to 70 years of age and follow-up lasted between 24 weeks to 7.5 years.

Piccoli underscored that these findings are only relevant for patients being treated with a GLP-1 receptor agonist for diabetes control or weight loss without pre-existing breast cancer. She added that patients with a history of breast cancer -- or any cancer -- were typically excluded from the trials that were included in this meta-analysis.

"We can say in a general population with type 2 diabetes and obesity, [GLP-1 receptor agonists] are safe," Piccoli said. But the class's safety in patients with a history of breast cancer is less certain, she added.

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