What is the analysis of the LEADER study (Liraglutide, Glucagon-like peptide-1 receptor agonist)?

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Last updated: April 28, 2025View editorial policy

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From the FDA Drug Label

In the VICTOZA treatment arm of the LEADER trial [see Clinical Studies (14.3)], 1932 (41.4%) patients had mild renal impairment, 999 (21.4%) patients had moderate renal impairment and 117 (2. 5%) patients had severe renal impairment at baseline. The LEADER trial analysis for liraglutide shows that:

  • 41.4% of patients had mild renal impairment
  • 21.4% of patients had moderate renal impairment
  • 2.5% of patients had severe renal impairment at baseline 1. No overall differences in safety or efficacy were seen in these patients compared to patients with normal renal function.

From the Research

Liraglutide is recommended as a first-line treatment for patients with type 2 diabetes who have established cardiovascular disease or are at high risk, due to its significant reduction in cardiovascular risk and mortality, as demonstrated in the LEADER study 2.

Key Findings

  • The LEADER study showed a 13% reduction in the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke compared to placebo 3.
  • Liraglutide also reduced cardiovascular death by 22% and all-cause mortality by 15% 3.
  • The recommended regimen is liraglutide 1.8 mg injected subcutaneously once daily, starting at 0.6 mg and titrating up weekly to minimize gastrointestinal side effects.
  • Treatment should be continued long-term as benefits increased over time in the study, which followed patients for a median of 3.8 years.

Mechanism of Action

  • Liraglutide works by enhancing glucose-dependent insulin secretion, suppressing glucagon release, slowing gastric emptying, and reducing appetite, which collectively improves glycemic control while providing cardiovascular protection 4.

Safety and Efficacy

  • Common side effects include nausea, vomiting, and diarrhea, which typically diminish over time.
  • Patients should be monitored for pancreatitis, though this rare complication was not significantly increased in the LEADER trial 3.
  • The study also found that liraglutide reduced the risk of glycaemic deterioration, defined as a specified change in HbA1c or a substantial intensification of insulin or oral antihyperglycaemic drug (OAD) 5.

Patient Selection

  • Liraglutide should be considered suitable for patients with type 2 diabetes with or without a history of heart failure, as the effects of liraglutide on major adverse cardiovascular events were consistent in both subgroups 2.

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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