What are the FDA‑approved prescription weight‑loss medications and how do their typical effects compare to GLP‑1 drugs?
Executive summary
A raft of FDA‑approved prescription weight‑loss medications exists beyond the spotlighted GLP‑1 class — older drugs like phentermine and orlistat remain approved even as GLP‑1s and related multimodal peptides transform outcomes with far larger average weight reductions in trials [1]. The newest development is an oral GLP‑1: the FDA approved the Wegovy pill (oral semaglutide), joining established injectables and promising competitors that deliver between roughly 11–22% average weight loss in pivotal studies, with gastrointestinal side effects as the most common tradeoff [2] [3] [1].
1. What the FDA has already approved: the full roster that appears in reporting
The modern FDA‑approved landscape includes longstanding drugs such as phentermine (marketed as Lomaira/Adipex‑P) and orlistat (Xenical/Alli) that were mainstays before the GLP‑1 era [1], while the GLP‑1 family and related agents now dominate headlines: semaglutide brands Ozempic and Wegovy, and tirzepatide marketed as Zepbound (a dual GIP/GLP‑1 agonist), are among the agents with obesity or diabetes indications noted in coverage [4] [3] [1]. Reporting also emphasizes that some GLP‑1s remain primarily diabetes drugs with weight benefits (Ozempic, Mounjaro) while others carry explicit obesity indications (Wegovy, Zepbound) [4] [3].
2. How much weight these drugs typically produce — trial figures and head‑to‑head context
Clinical trial results cited in reporting show a clear hierarchy: tirzepatide produced the largest mean reductions in major trials — up to about 21–22.5% body weight at higher doses in SURMOUNT‑1 and related studies — while semaglutide formulations produced roughly 14–15% in pivotal trials; the oral Wegovy pill showed about 13.6–14% mean weight loss in its OASIS‑4 trial versus placebo [1] [5] [3]. Separate company data on orforglipron (Lilly’s oral candidate) reported approximately 11% weight loss at its highest dose versus placebo in its phase‑3 readouts, while placebos were typically near 2–3% [3].
3. Side effects, adherence and practical differences between pills and injections
Across reporting, gastrointestinal symptoms — nausea, vomiting and treatment discontinuation in a minority — are the most common adverse effects for GLP‑1s whether injectable or oral, with trial dropouts for side effects modest but present (for example, ~7% stopped the Wegovy pill for side effects in one trial) [3] [6]. Practical differences matter: oral semaglutide requires dosing and absorption considerations distinct from weekly injectables, and some oral formulations historically delivered lower exposures than injections; injectables require refrigeration but have shown slightly different dosing curves in trials [7] [3].
4. How GLP‑1s compare to older, non‑GLP‑1 anti‑obesity drugs in effect size and role
Older agents such as phentermine and orlistat are still FDA‑approved and play roles in short‑term or adjunctive care, but reporting portrays them as delivering much smaller average weight losses than modern GLP‑1 and multi‑agonist peptides — a key reason GLP‑1s have reshaped treatment expectations [1]. The newest entrants that combine hormones (GIP/GLP‑1 or triple agonists like retatrutide in development) aim to exceed current GLP‑1 results, with industry trials and corporate commentary pointing to even larger losses for some candidates [4] [8].
5. Access, price and hidden agendas shaping the narrative around GLP‑1s
Coverage highlights that cost and access are central to the public debate: manufacturers and the U.S. executive branch negotiated lower self‑pay prices and programs (e.g., $149 starter pricing under recent deals), and oral pills are predicted to be cheaper to produce and distribute than injectables, which could broaden access — a commercial and political win for companies and policymakers alike [8] [9] [10]. Those same pricing arrangements and marketing incentives create competing agendas: drugmakers benefit from expanded markets and favorable pricing narratives, while policymakers frame deals as consumer relief even as insurers and clinicians continue to weigh coverage criteria and BMI thresholds [8] [11].
6. Limits of current reporting and what remains unanswered
Reporting provides trial effect sizes and regulatory milestones but does not resolve long‑term durability beyond the durations reported, optimal patient selection, or head‑to‑head comparisons across every new oral and injectable agent; some pills and next‑generation triple‑agonists remain in trials and unapproved as of these reports, so comparisons rely on separate trials rather than randomized direct comparisons [3] [8] [4].