The trial program has evolved from glycemic-safety and outcomes studies in T2D (the LEADER, SUSTAIN-6, REWIND, EXSCEL, and PIONEER 6 era [10][13], [19]), to outcomes trials in expanded populations including obesity without diabetes (SELECT [3]), HFpEF with obesity (SUMMIT [5], with a companion semaglutide program in STEP-HFpEF [20], [21]), CKD (FLOW [22]), and an active-comparator setting (SURPASS-CVOT [6])
For molecules excluded from oral development, this review has surveyed realistic alternatives that deserve systematic consideration: pulmonary delivery for rapid-onset needs, nasal delivery for rescue applications, buccal/sublingual delivery for potent peptides accommodating variability, and most importantly, long-acting injectables, depots, implants, and pumps that often outperform oral approaches on pharmacokinetic predictability and total cost
The pill works through the same mechanism as the injection
Semaglutide is now backed by strong evidence showing it can do more than help with weight or diabetes: It can lower the risk of heart attacks, strokes, and cardiovascular death, including in people without diabetes who already have heart disease
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