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Among patients with type 2 diabetes and tobacco use disorder (TUD), use of the GLP-1 receptor agonist semaglutide (Ozempic, Wegovy) was associated with a reduced risk of medical encounters for TUD compared with other diabetes medications, according to an emulation target trial.

Using a nationwide population-based database of electronic health records, the strongest association with a reduced risk of medical encounters for TUD diagnosis, smoking cessation medication prescriptions, and smoking cessation counseling was observed when semaglutide was compared with insulins (HR 0.68, 95% CI 0.63-0.74), reported Nora D. Volkow, MD, director of the National Institute on Drug Abuse, and colleagues.

The association was weakest, but still statistically significant, when semaglutide was compared with other GLP-1 drugs (HR 0.88, 95% CI 0.81-0.96), they noted in the .

Findings were consistent across patients with and without obesity, and differences occurred within 30 days of prescription initiation for most of the group comparisons.

Patients taking semaglutide reported that they had a "reduced desire to smoke," lending support for the drug as a smoking cessation tool, Volkow and colleagues said.

They pointed to a that suggested that semaglutide was linked to reduced incidence and relapse of cannabis use disorder, as well as a in patients with obesity or prediabetes that showed that exenatide (Byetta, Bydureon) plus nicotine replacement therapy improved abstinence from smoking compared with placebo.

"The fact that semaglutide (and other GLP-1 receptor agonists) leads to weight loss becomes particularly relevant because smoking cessation is associated with weight gain, which contributes to relapse, particularly in women," Volkow's group wrote. "Moreover, because smoking impairs glycemic control and increases cardiovascular and cancer risks, the beneficial effects of semaglutide for glycemic control, and reduction in cardiovascular and cancer events, would offer additional benefits."

Semaglutide also has a higher adherence rate than other medications, including other GLP-1 drugs, in patients with type 2 diabetes, they added.

For this study, seven target trials were emulated among 222,942 eligible patients with type 2 diabetes and TUD by comparing the new use of semaglutide (n=5,967) versus other diabetes medications (n=216,975), including insulins, metformin, DPP-4 inhibitors, SGLT2 inhibitors, sulfonylureas, thiazolidinediones, and other GLP-1 receptor agonists (albiglutide [Tanzeum], dulaglutide [Trulicity], exenatide, liraglutide [Saxenda, Victoza], and lixisenatide [Adlyxin]).

Eligible patients had a medical encounter with a healthcare organization from December 2017 through March 2023; a diagnosis of type 2 diabetes and TUD before an index event (medical encounters for TUD diagnosis, smoking cessation medication prescriptions, and smoking cessation counseling); and a diagnosis of obesity, hypertension, hypercholesterolemia, hyperlipidemia, heart diseases, or stroke before an index event.

Patients were excluded if they had previously used a diabetes medication in the year before an index event; a history of bariatric surgery, pancreatitis, type 1 diabetes, thyroid cancer, or gastroparesis; or co-prescription of semaglutide and other diabetes medications on the index event date.

Patients were followed from the index event until the occurrence of the measure, death, loss to follow-up, or 12 months after the index event, whichever occurred first.

After propensity-score matching for the semaglutide and insulin groups, mean age at index event was about 59, and women made up half of each group. Most patients were white (69%), 11.8% were Black, and about 4% were Asian.

Among patients without obesity, semaglutide was associated with a significantly lower risk for medical encounters for TUD diagnosis compared with other diabetes medications, with hazard ratios ranging from 0.60 for insulin (95% CI 0.51-0.71) to 0.78 for thiazolidinediones (95% CI 0.64-0.94), with the exception of other GLP-1 drugs (HR 0.85, 95% CI 0.71-1.02).

Among patients with a prior diagnosis of obesity, semaglutide was associated with a significantly lower risk for medical encounters for TUD diagnosis compared with all included diabetes medications.

Additionally, semaglutide was associated with a significantly lower risk for a prescription for a smoking cessation medication compared with other diabetes medications, with the strongest association when compared with insulins (HR 0.32, 95% CI 0.28-0.38) and weakest compared with other GLP-1 drugs (HR 0.62, 95% CI 0.52-0.74). This association was observed regardless of obesity diagnosis.

Semaglutide was also linked to a lower risk of smoking cessation counseling, and was significant when compared with insulins, metformin, and DPP-4 inhibitors, with hazard ratios ranging from 0.69 to 0.85.

Volkow and colleagues listed the study's retrospective, observational design among its key limitations. Other limitations included a shorter follow-up time, a limited sample size for comparison with other anti-obesity medications, and missing data regarding medication adherence.

They also stressed that this study was an early foray into using semaglutide for smoking cessation and the results "should not be interpreted to justify clinicians' use of semaglutide off-label for smoking cessation. This will need to be examined in randomized clinical trials."

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