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Long-Term Efficacy Trajectories of GLP-1 Receptor Agonists: A Systematic Review and Network Meta-Analysis

Zixuan Li1, Zhoubo Han1, Rong Sun2

  • 1Department of Endocrinology, Bishan Hospital of Chongqing Medical University, Bishan, Chongqing, 402760, People's Republic of China.

Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy
|September 29, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively manage type 2 diabetes long-term, improving glycemic control and aiding weight loss. However, their efficacy diminishes after two years, necessitating careful consideration of treatment duration.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia.
  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of medications increasingly used for T2DM management.
  • Understanding the long-term efficacy and evolving effects of GLP-1RAs is crucial for optimizing patient care.

Purpose of the Study:

  • To evaluate the sustained effectiveness and changing treatment trajectories of GLP-1RAs in patients with type 2 diabetes.
  • To analyze the long-term impact of GLP-1RAs on key metabolic parameters and body weight.

Main Methods:

  • A comprehensive meta-analysis was conducted, searching PubMed, Embase, and Cochrane Library databases up to March 2024.
  • Included randomized controlled trials (RCTs) comparing GLP-1RAs with placebo.
  • Subgroup analyses were performed based on various follow-up durations (12-104+ weeks) to assess temporal effects.

Main Results:

  • Fifty-five trials with 18,876 participants demonstrated that GLP-1RAs significantly improve HbA1c, body weight, fasting plasma glucose (FPG), systolic blood pressure, and serum lipids.
  • Continuous reductions in HbA1c and FPG were observed for at least 104 weeks, though effects lessened compared to earlier time points.
  • Optimal weight loss occurred at 24-30 weeks, followed by a plateau; increased risks of hypoglycemia and gastrointestinal events were noted.

Conclusions:

  • GLP-1RAs are recommended for long-term type 2 diabetes treatment owing to sustained glycemic control and weight loss benefits.
  • The diminishing efficacy after two years warrants consideration in treatment strategies.
  • Monitoring for adverse events like hypoglycemia and gastrointestinal issues is essential.
Keywords:
glucagon-like peptide 1 receptor agonistsnetwork meta-analysissystematic reviewtype 2 diabetes

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