A simple fasting blood test could one day help physicians determine which obesity medication is most likely to deliver the best results for individual patients, according to a preliminary study published in the journal Diagnostics.
Researchers found that fasting blood levels of two key incretin hormones—glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)—may predict how people with severe obesity respond to two widely used weight-loss drugs: semaglutide and tirzepatide.
Obesity affects more than 650 million adults worldwide and is associated with a higher risk of cardiovascular disease, type 2 diabetes, several cancers, and premature death. Although GLP-1-based therapies have revolutionized obesity treatment, patients often experience highly variable weight-loss outcomes, underscoring the need for more personalized treatment strategies.
To investigate whether hormone levels could guide drug selection, researchers from the University of Catania and MEDISAN in Italy enrolled 90 adults with class III obesity (body mass index above 40 kg/m²). Participants underwent fasting blood tests to measure GLP-1 and GIP concentrations before being randomly assigned to receive either semaglutide or tirzepatide. Treatment response was evaluated after six months.
The findings showed that participants with low fasting GIP levels consistently achieved the greatest weight loss with tirzepatide, regardless of their GLP-1 levels. In contrast, semaglutide produced the best results in individuals with low GLP-1 levels combined with intermediate or high GIP concentrations.
Researchers also observed that participants with both high GLP-1 and high GIP levels responded poorly to both medications, suggesting that alterations in the incretin system may reduce treatment effectiveness. However, the authors emphasize that this explanation remains speculative because fasting hormone measurements cannot distinguish between reduced hormone production and receptor resistance.
Patients who achieved the greatest weight loss also experienced significant reductions in waist circumference and improved insulin sensitivity, indicating meaningful metabolic benefits beyond weight reduction.
The researchers believe these findings could pave the way for personalized obesity treatment, allowing physicians to select medications based on an individual's hormonal profile rather than relying on trial and error. However, they stress that the results are preliminary. The study included only 90 participants and was conducted at a single center, with just five patients receiving each medication within each hormone profile.
Larger randomized clinical trials will be required before fasting GLP-1 and GIP testing can be recommended for routine clinical practice.
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