Introduction:
Research related to GLP-1 is reshaping our understanding at an unprecedented pace. Beyond weight loss and blood sugar control, scientists are continuously exploring its broader application potential and underlying mechanisms. Several groundbreaking studies released in 2025 have opened new doors to our comprehension of GLP-1. This article provides an in-depth interpretation of three key studies among them.

Study 1: Wegovy® Approved for MASH Treatment—A New Era in Liver Disease Therapy
Source: Novo Nordisk ESSENCE Phase III Trial (Stage 1)¹

Key Findings:

• After 72 weeks of treatment, 36.8% of metabolic dysfunction-associated steatohepatitis (MASH, formerly known as NASH) patients with moderate to severe liver fibrosis who received Wegovy® (semaglutide 2.4mg) achieved liver fibrosis improvement without worsening of steatohepatitis, compared to 22.4% in the placebo group¹.

• 62.9% of the treatment group achieved steatohepatitis improvement without worsening of liver fibrosis, compared to 34.3% in the placebo group¹.

• Based on these results, the FDA has granted accelerated approval for Wegovy® to treat non-cirrhotic adults with MASH and moderate to severe liver fibrosis¹.

Expert Interpretation:

• Significance: MASH is a severe and progressive liver disease, and there has been a global lack of approved effective drugs. Wegovy®’s success offers the first and only GLP-1-based treatment option for such patients¹.

• Mechanism Insight: GLP-1 drugs may improve liver pathology through multiple pathways, including significant weight loss, improved insulin resistance, and direct anti-inflammatory and anti-fibrotic effects.

• Outlook: The approval of this indication significantly expands the application scope of GLP-1 drugs, bringing hope to millions of MASH patients. The second stage of the trial is expected to be released in 2029, providing longer-term efficacy and safety data¹.

Study 2: Breakthroughs and Challenges of Oral GLP-1/GIP Dual Agonists
Source: Viking Therapeutics VK2735 Phase II VENTURE-Oral Trial⁴⁷

Key Findings:

• After 13 weeks of daily oral VK2735 (a GLP-1/GIP dual agonist), the highest dose group (120mg) achieved an average weight loss of 12.2% (approximately 26.6 pounds), compared to 1.3% (approximately 2.9 pounds) in the placebo group⁴⁷.

• Safety: Most gastrointestinal adverse events (99%) were mild to moderate⁴. However, the treatment discontinuation rate was high (28% overall in the VK2735 group vs. 18% in the placebo group), and two treatment-related serious adverse events occurred in the highest dose group⁸.

Expert Interpretation:

• Convenience and Accessibility: The success of oral formulations offers a potential alternative for patients unable or unwilling to undergo injection therapy, potentially greatly improving patient compliance and drug accessibility.

• Balancing Efficacy and Safety: Although weight loss effects are significant, the high discontinuation rate and gastrointestinal side effects indicate that tolerability remains a key issue to be optimized in future development⁸.

• Market Prospects: Despite meeting Phase II endpoints, the market response has been cautious, reflecting investors’ higher demands for the efficacy and safety profile of oral GLP-1 drugs. The field is highly competitive, with players like Eli Lilly and Novo Nordisk also making strides⁸.

Study 3: Hidden Risks in GLP-1 Therapy—Nutritional Deficiencies and Muscle Loss
Source: Large Retrospective Study in Obesity Pillars (n=461,382)⁶

Key Findings:

• Among type 2 diabetes patients treated with GLP-1 receptor agonists, approximately 22.4% were diagnosed with nutritional deficiencies within 12 months, with vitamin D deficiency being the most common (13.6%). The diagnosis rate for muscle loss was 3%⁶.

• The incidence of nutritional deficiencies in the GLP-1 group was significantly higher than in the metformin-only control group (18.6% vs. 16.5%)⁶.

Expert Interpretation:

• Revealing a Blind Spot in Management: This large-scale study is the first to quantify the malnutrition issues accompanying GLP-1 therapy, reminding clinicians and patients not to focus solely on the numbers on the scale.

• Cause Analysis: Appetite suppression leading to reduced overall food intake is the primary cause of nutritional deficiencies and muscle loss. Approximately 38% of weight loss comes from lean body mass (including muscle), which can impact metabolic rate and long-term health⁶.

• Clinical Recommendations: Experts strongly recommend incorporating nutritional monitoring and management as a standard component of GLP-1 therapy, including:

  • Regular Screening: Monitor levels of key nutrients such as vitamin D and B12⁶.

  • Adequate Protein Intake: Recommend a daily intake of 1.2–1.6 grams of protein per kilogram of body weight⁶.

  • Combined Resistance Training: Engage in strength training at least twice a week to help preserve or even increase muscle mass⁶.

Conclusion:
The scientific frontier of GLP-1 is shifting from “whether it is effective” to “how to apply it better, safer, and more broadly.” These latest studies not only bring new therapeutic hope but also reveal risks that require vigilance. For users, maximizing benefits and minimizing risks ultimately depends on working under medical guidance, adopting a healthy lifestyle, and prioritizing nutritional balance.