What a real-world study found comparing semaglutide and liraglutide

Two medications in the GLP-1 receptor agonist class, semaglutide and liraglutide, are both approved for chronic weight management. Researchers writing in the British Journal of Clinical Pharmacology wanted to know something more specific: when compared head to head, does one lower the risk of newly developing diabetes or cardiovascular disease more than the other?

This was a study of real-world insurance claims data, not a laboratory experiment and not a randomized trial. It involved people, using records from the MarketScan claims databases. The authors used a method called target trial emulation, which tries to mimic the structure of a randomized trial using data that was already collected.

What the researchers studied

The team used what is called an active comparator, new user design. In plain terms, they compared people who were newly starting semaglutide against people who were newly starting liraglutide, rather than comparing either drug to nothing. Everyone included was free of diabetes and cardiovascular disease at the start, and had been prescribed one of the two drugs during 2021 through 2023.

They matched users one to one, ending up with 57,456 GLP-1 users. The average age was 45, and 83 percent were female. Follow-up averaged about one year. The main outcomes they tracked were newly diagnosed diabetes and cardiovascular events, defined as myocardial infarction, heart failure, or stroke.

What they reported

Over roughly a year of follow-up, there were 1,104 diabetes events and 57 cardiovascular events. After statistical adjustment using a propensity score that accounted for other health conditions and medications, semaglutide users had a 12 percent lower risk of developing diabetes than liraglutide users (hazard ratio 0.88, 95% confidence interval 0.78 to 0.99).

That difference was not steady across time. During the first six months, the two drugs looked the same for diabetes risk (hazard ratio 0.99). The lower risk with semaglutide showed up only after that point (hazard ratio 0.80 in the later period). For cardiovascular events, the study did not detect a difference between the two drugs (hazard ratio 1.25, with a wide confidence interval of 0.74 to 2.11).

What this does and does not establish

For someone weighing physician-prescribed care, the honest reading is narrow. The study suggests that, in this population, semaglutide users had a lower one-year risk of a new diabetes diagnosis than liraglutide users. It compares two active drugs against each other, not against no treatment, so it says nothing about how either compares to taking nothing at all.

Because this is observational data rather than a randomized trial, it can show an association but cannot prove that the drug caused the difference. People who received one drug may differ from those who received the other in ways the researchers could not fully measure. The statistical matching reduces that concern but does not remove it.

On cardiovascular disease, the study is clear about its own limits. With only 57 cardiovascular events across a large group, there simply were not enough of them to draw a reliable conclusion. The wide confidence interval reflects that uncertainty, and the authors explicitly call for more research on comparative cardiovascular effects.

One honest limitation

The follow-up averaged about one year. That is a short window for outcomes like diabetes and cardiovascular disease, which develop over many years. The finding that semaglutide's lower diabetes risk appeared only after the first six months also means the earliest period showed no difference. What happens over three, five, or ten years is outside what this study can answer.

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