Oral GLP-1 Receptor Agonists Danuglipron and Orforglipron found effective in controlling blood sugar and weight: Study

A new meta-analysis published in the journal of Frontiers in Endocrinology revealed that oral GLP-1 receptor agonists danuglipron and orforglipron improve glycemic control and promote weight loss, but are associated with a higher risk of gastrointestinal adverse events. However long-term longitudinal studies are needed to better define their efficacy, safety, and tolerability.

The study systematically reviewed and pooled data from 8 randomized controlled trials involving 1,454 participants with T2DM and/or obesity. This research searched major medical databases including PubMed, Web of Science, the Cochrane Library and Embase for studies published up to 20 May 2025. The goal of this study was to assess how well the two oral GLP-1 receptor agonists lowered blood sugar and body weight and how safe they were for patients.

The findings indicate that both drugs produced meaningful metabolic improvements. Danuglipron significantly reduced glycated hemoglobin (HbA1c), a key marker of long-term blood sugar control, by nearly one percentage point on average. It also lowered fasting plasma glucose and led to modest but significant weight loss. Importantly, danuglipron increased fasting plasma insulin levels, suggesting improved pancreatic insulin response.

Orforglipron showed even more striking weight-related benefits. In addition to lowering HbA1c and fasting glucose by roughly similar or slightly greater margins than danuglipron, it produced an average weight reduction of more than 6 kilograms and significantly decreased body mass index (BMI). These findings position orforglipron as a particularly promising option for patients struggling with both diabetes and obesity.

The study compared baseline and post-treatment values across all included trials which focused on efficacy outcomes, listing average changes in HbA1c, fasting glucose, fasting insulin, weight and BMI for each drug.

This study reported the proportion of participants experiencing treatment-related adverse events and, more specifically, gastrointestinal symptoms such as nausea, vomiting and diarrhoea. These tables revealed that both danuglipron and orforglipron were linked to higher rates of GI side effects when compared to control groups, a pattern similar to injectable GLP-1 therapies already on the market.

Overall, danuglipron and orforglipron represent a promising next generation of diabetes and weight-loss medications, powerful in effect, convenient in form, but not without side-effect considerations that clinicians will need to manage carefully.

Source:

Zhou, J., Wang, F., & Li, S. (2025). The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis. Frontiers in Endocrinology, 16(1646956), 1646956. https://doi.org/10.3389/fendo.2025.1646956