Liraglutide is one of the GLP-1 receptor agonists with the most extensive clinical evidence and the longest history of use. At a time when semaglutide and tirzepatide dominate public discourse due to their superior weight-loss efficacy, the clinical value of liraglutide warrants re-examination; it is by no means an "obsolete" choice but rather a treatment option with clear, evidence-based support for specific patient populations and clinical scenarios.
I. Core Efficacy: Dual Evidence of Weight Loss and Cardiovascular Protection
There is a clear dose-response relationship regarding weight loss. In pivotal Phase III trials, once-daily administration of 3.0 mg liraglutide in adults with obesity or overweight demonstrated clinically significant weight reduction. Real-world data further corroborate this effect: a multicenter study involving 1,009 patients with obesity showed that 76.4% achieved a 5% weight loss target, while 40.9% achieved a 10% target. Another real-world study from Turkey (n=568) reported a mean weight loss of 19 kg (approximately 18.55%) over 24 weeks. It should be noted that high completion rates in real-world studies may be subject to selection bias; however, the overall weight-loss trend remains consistent with that observed in randomized controlled trials.
Cardiovascular protection is a key advantage distinguishing liraglutide from drugs intended solely for weight loss. The LEADER trial (n=9,340) confirmed that liraglutide significantly reduced the risk of major adverse cardiovascular events (MACE) (HR 0.87) in patients with type 2 diabetes and high cardiovascular risk. Even more compelling is a "transportability" analysis published in 2025: when the treatment effects observed in the LEADER trial were extrapolated to the US Veterans Affairs healthcare system (n=357,075), the absolute risk difference over three years was 2.0% for MACE and 1.5% for all-cause mortality-with effect sizes overlapping those of the original trial. This indicates that the cardiovascular benefits of liraglutide are generalizable to high-risk real-world populations, rather than being merely a "trial effect" limited to strict enrollment criteria. II. Positioning within the GLP-1 Family: Not the Best, Yet Irreplaceable
When compared directly with other drugs in the same class, liraglutide has clear disadvantages. Head-to-head studies (such as STEP 8) demonstrate that the once-weekly 2.4 mg formulation of semaglutide is significantly superior to the once-daily 3.0 mg formulation of liraglutide in terms of weight loss efficacy. A real-world study in Kuwait also found that users of tirzepatide reported greater monthly weight loss (4.76 kg) and higher satisfaction rates (88%) compared to liraglutide users.
However, liraglutide offers unique value in three respects: First, it is currently the only GLP-1 drug supported by randomized controlled trial evidence for treating obesity in children (aged 6–12); the SCALE Kids trial provides the data backing its use in this age group. Second, the LEADER trial stands as one of the longest-running studies in the GLP-1 field, featuring the most rigorous adjudication of cardiovascular endpoints; the robustness of its evidence cannot be matched by short-term weight-loss trials. Third, the FDA has approved multiple generic versions of liraglutide, making it significantly more cost-accessible than semaglutide and tirzepatide, which remain under patent protection.
III. Safety and Tolerability: Gastrointestinal Reactions Requiring Management
Liraglutide's safety profile is consistent with that of other drugs in its class. The most common adverse reactions are gastrointestinal symptoms; real-world studies show that 48% of patients report at least one adverse reaction, with nausea and vomiting being the most frequent. A German review characterizes these reactions as "mild to moderate," noting that they typically subside as treatment progresses.
The primary concern is not the common side effects, but rather real-world adherence issues. In the aforementioned Turkish study, the leading reason for discontinuing treatment was cost (42.6%) rather than adverse reactions. The Kuwaiti survey also found relatively high levels of anxiety and medication-switching rates among liraglutide users. These data suggest that the "effectiveness" of liraglutide depends not only on the drug itself but also on the patient's ability to sustain long-term treatment-both financially and psychologically. IV. Recommendation Rationale: Who Is It For?
Recommended for:
Patients with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular risk factors-evidence for cardiovascular benefit is most robust.
Obese children aged 6–12-currently the only GLP-1 option supported by randomized controlled trial (RCT) evidence.
Patients unable to access or tolerate semaglutide or tirzepatide-liraglutide serves as a reasonable alternative.
Patients experiencing weight regain after bariatric surgery-small-scale studies support its efficacy as an adjunct for weight loss.
Situations where other options should be prioritized:
Adult patients prioritizing maximum weight loss-semaglutide or tirzepatide offer superior weight-loss efficacy.
Patients unable to tolerate daily injections-once-weekly formulations offer better adherence.
In its 2026 guidelines on GLP-1 therapy for obesity, the WHO issued a conditional recommendation for combining GLP-1 therapy with intensive behavioral therapy, emphasizing that while efficacy is clear, long-term data, cost, and equitable access remain limiting factors. As the first drug in this class to see widespread availability of generics, liraglutide holds a structural advantage regarding accessibility.
Conclusion
Liraglutide may not be the "most potent" GLP-1, but it boasts the most robust evidence base, the best accessibility, and unique data regarding specific patient populations. In an era dominated by semaglutide and tirzepatide, liraglutide's clinical role should be viewed as follows: a priority option for diabetic patients at high cardiovascular risk, a limited yet clear choice for pediatric obesity, and a pragmatic solution capable of delivering clinically significant weight loss in resource-constrained settings. Whether to recommend it depends on how "efficacy" is defined: if the sole criterion is the magnitude of weight loss, it is not the first choice; however, if cardiovascular protection, suitability for specific populations, and long-term affordability are included, it remains worthy of serious consideration.