First approved obesity GLP-1 pill (peptide formulation). Marketed dose is 25 mg; OASIS 4 (Wharton NEJM 2025, NEJMoa2500969) is the registrational paper for that dose. n=205 oral sema + n=102 placebo, 71-wk trial, week 64 primary. Treatment-policy estimand -13.6% (efficacy estimand -16.6%). AE-led disc 14/205 (6.9%) vs 6/102 (5.9%) placebo. The higher-dose 50 mg OASIS-1 (Knop Lancet 2023) showed -15.1% but is not the approved dose. Requires fasting administration. 3M Rx in 5 mo of launch.
Higher-dose semaglutide (Wegovy 7.2 mg), FDA-approved 2026 under the National Priority Voucher program (4th product). STEP UP (Wharton et al, NCT05646706, Lancet Diabetes Endocrinol 2025, DOI S2213-8587(25)00226-8): 72-wk obesity without T2D (n=1005 at 7.2 mg), 7.2 mg -18.7% (treatment-policy, stored) and -20.7% (trial-product, adherent) at wk 72 vs 2.4 mg -15.6%/-17.5% and placebo -3.9%; 47.7% reached >=20% and 31.2% >=25% weight loss. Tolerability strong despite the higher dose (16-wk titration): total AE-led permanent discontinuation 5.4% (54/1004; appendix Suppl Table 8) vs 4.0% at 2.4 mg and 1.0% placebo - directly comparable, so plotted as a normal scatter marker. Of that, GI-led 3.3% and nervous-system/dysaesthesia 0.8%; GI AEs 70.8%, SAEs 6.8%, no deaths. Trajectory from Figure 2A (in-trial/treatment-policy curve). Distinct from STEP UP T2D (separate diabetes trial, -13.2%).
Indication
Type 2 diabetes
Delivery
subQ · weekly
Top dose
2.0 mg
Status
approved 2017
Diabetes formulation of Semaglutide - shown for context. The obesity SKUs are on the other tabs; obesity efficacy comparisons on this site cover obesity SKUs only.
Once-weekly injectable GLP-1 for type 2 diabetes (also indicated for cardiovascular risk reduction). Same molecule as Wegovy, at lower doses (up to 2.0 mg vs 2.4 mg). Pivotal SUSTAIN phase 3 program.
Indication
Type 2 diabetes
Delivery
oral · daily
Top dose
14 mg
Status
approved 2019
Diabetes formulation of Semaglutide - shown for context. The obesity SKUs are on the other tabs; obesity efficacy comparisons on this site cover obesity SKUs only.
First oral GLP-1 (semaglutide co-formulated with the absorption enhancer SNAC), once-daily for type 2 diabetes. Pivotal PIONEER phase 3 program. The obesity-dose oral semaglutide (25 mg) is the separate Wegovy-oral tab.
