Effect of Oral Semaglutide With or Without Background SGLT2i in Patients with T2D: Subgroup Analysis of PIONEER 4
Semaglutide is a long-acting GLP-1 receptor agonist used to control hyperglycemia in patients with type 2 diabetes. It has been coformulated with the absorption enhancer SNAC to enable administration as a once-daily tablet. In PIONEER 4, oral semaglutide was compared with placebo and the once-daily injectable GLP-1 receptor agonist liraglutide in patients whose type 2 diabetes was not adequately controlled on metformin, with or without an SGLT2 inhibitor. Approximately one quarter of patients were receiving an SGLT2 inhibitor at baseline.
Patients receiving GLP-1 receptor agonist therapy had reductions in A1C at the end of treatment of just over 1%. These reductions were similar regardless of whether patients were receiving background SGLT2 inhibitor treatment or not. GLP-1 receptor agonist therapy was associated with mean reductions in body weight of 5 kilograms with oral semaglutide, and 3 to 3.7 kilograms with liraglutide. Changes in body weight with oral semaglutide were unaffected by whether patients were receiving an SGLT2 inhibitor or not. GLP-1 receptor agonist therapy was associated with GI adverse events, as expected. Most individual gastrointestinal adverse events occurred at a similar incidence regardless of concomitant SGLT2 inhibitor use. In conclusion, existing treatment with a SGLT2 inhibitor did not substantially affect efficacy and safety outcomes with oral semaglutide or liraglutide after one year of treatment.
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