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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

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

Another approach employed to increase levels of endogenous GLP1 is the inhibition of DPP4, an enzyme responsible for the degradation of GLP1 and other peptides, by compounds such as sitagliptin

E., Weigel M

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