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Whether orforglipron's effects on bone health are net positive (through receptor-mediated bone protection) or net negative (through sustained caloric deficit and weight loss reducing mechanical loading on bones) will need to be determined through long-term surveillance studies

That includes patients with severe obesity, significant metabolic disease, or a history of losing and regaining weight repeatedly

In contrast, those who took orforglipron regained just 26%, with over two-fifths of participants maintaining over 80% of their body weight reduction

A subsequent analysis of SELECT trial data presented at the 2025 European Congress on Obesity found that the heart benefits appeared within just a few weeks of starting the medication and were not entirely explained by weight loss alone