SemaglutideComparisonMarch 2026
ORION study: Oral Wegovy shows more weight loss than Foundayo in indirect comparison
An indirect comparison (ORION study) matching patients across the OASIS-4 and ATTAIN-1 trials found oral semaglutide 25mg showed about 3.2 percentage points more weight loss than orforglipron 36mg. Orforglipron was associated with about 4 times higher odds of stopping treatment. This is not a head-to-head trial — it used statistical matching across separate studies. Funded by Novo Nordisk.
CagriSemaFDA FilingDecember 2025
Novo Nordisk files CagriSema for FDA approval — first GLP-1 + amylin combination
Novo Nordisk submitted a New Drug Application (NDA) to the FDA on December 18, 2025 for CagriSema, a once-weekly injection combining cagrilintide (amylin analogue) and semaglutide. In the REDEFINE 1 trial, participants lost an average of 22.7% body weight with full adherence. FDA decision expected late 2026 to early 2027.
AmycretinPhase 2January 2026
Amycretin shows 14.5% weight loss in 36 weeks in Phase 2 diabetes trial
Novo Nordisk's amycretin (a single molecule combining GLP-1 and amylin activity) achieved 14.5% weight loss in 36 weeks in a Phase 2 type 2 diabetes trial — a rapid rate that could challenge current leaders. Up to 89.1% of patients reached HbA1c below 7%. Phase 3 trials for obesity are expected to begin in early 2026.
MariTidePhase 22025
MariTide achieves up to 20% weight loss at 52 weeks — once-monthly injection
Amgen's MariTide (maridebart cafraglutide), a once-monthly GIP receptor antagonist and GLP-1 agonist, showed up to 20% weight loss at 52 weeks in a Phase 2 trial — with weight loss still declining (no plateau). Phase 3 trials have been initiated for chronic weight management with 72-week endpoints.
OrforglipronPhase 3February 2026
ACHIEVE-3: Orforglipron showed greater weight loss than oral semaglutide in a head-to-head diabetes trial
In the ACHIEVE-3 trial (1,698 adults with type 2 diabetes), orforglipron 36mg showed greater weight loss (9.2% vs 5.3%) and blood sugar control than oral semaglutide 14mg. However, this used the diabetes dose of semaglutide (14mg), not the higher 25mg obesity dose. Discontinuation from side effects was higher with orforglipron (9.7% vs 4.9%).
FDA ApprovedOrforglipronApril 2026
FDA approves Foundayo (orforglipron) — Lilly's oral GLP-1 pill with no food restrictions
The FDA approved Foundayo (orforglipron) on April 1, 2026 — the first oral GLP-1 weight loss pill with no food or water timing restrictions. Available via LillyDirect starting April 6, priced by dose from $149/month self-pay up to $349/month, or $25/month with commercial insurance. In the ATTAIN-1 trial, participants lost an average of 12.4% body weight at the highest dose. Unlike oral Wegovy, Foundayo can be taken any time of day without fasting.
FDA ApprovedSemaglutideDecember 2025
FDA approves Wegovy pill — the first oral GLP-1 for weight loss
The FDA approved oral semaglutide 25mg (Wegovy pill) on December 22, 2025 — the first oral GLP-1 drug approved for weight loss. It launched in the US in January 2026 at ~$149/month self-pay for the starting dose, dramatically cheaper than the weekly injection (~$1,350/month list price). In the OASIS 4 trial (307 adults, 64 weeks), participants lost an average of 13.6% of body weight (16.6% with full adherence). The pill requires a 30-minute fasting window before eating.
TirzepatidePhase 32025
Tirzepatide beats semaglutide in first head-to-head trial
The SURMOUNT-5 trial — the first direct head-to-head comparison of tirzepatide and semaglutide in people with obesity — found tirzepatide superior on body weight reduction and waist circumference at 72 weeks.
CagriSemaPhase 32025
CagriSema achieves 20.4% weight loss in REDEFINE 1
The REDEFINE 1 phase 3 trial of CagriSema (cagrilintide + semaglutide) in 3,417 adults without type 2 diabetes showed 20.4% average weight loss and 22.7% with full adherence. 50.7% of participants reached a healthy BMI.
OrforglipronPhase 32025
Orforglipron: oral GLP-1 pill achieves 12.4% weight loss in Phase 3
The ATTAIN-1 trial of orforglipron — the first oral small-molecule GLP-1 agonist to complete Phase 3 — showed 12.4% mean weight loss at the highest dose (36 mg) over 72 weeks. An FDA NDA was submitted in 2025.
SemaglutideCardiovascular2023
Semaglutide reduces heart attacks and strokes by 20% — SELECT trial
The SELECT trial (n=17,604) demonstrated that semaglutide 2.4 mg reduced major adverse cardiovascular events by 20% vs. placebo in adults with established CVD and obesity without diabetes — the first weight loss drug to show this effect.
RetatrutidePhase 22023
Retatrutide Phase 2: 24.2% average weight loss at 48 weeks
Phase 2 results for retatrutide (triple GIP + GLP-1 + glucagon agonist) showed up to 24.2% mean weight loss at 48 weeks — without plateau. All participants at 8 mg and 12 mg achieved ≥5% weight loss. Phase 3 (TRIUMPH) now underway.
TirzepatideWeight regain2024
Stopping tirzepatide leads to significant weight regain — SURMOUNT-4
In the SURMOUNT-4 trial, participants who switched from tirzepatide to placebo regained an average of 14% body weight over 52 weeks. Only 16.6% maintained 80%+ of their prior weight loss, vs. 89.5% who continued tirzepatide. Confirms that obesity requires chronic treatment.
AmycretinPhase 12024
Amycretin oral pill shows 13.1% weight loss in 12 weeks — beating oral semaglutide
Early Phase 1 data for Novo Nordisk's amycretin (GLP-1 + amylin single molecule) in oral form showed 13.1% weight loss in 12 weeks vs. 1.1% placebo — outperforming oral semaglutide at the same timepoint. Phase 3 planned for Q1 2026.
OrforglipronPhase 32025
Patients switching from injections to orforglipron pill maintain their weight loss
The ATTAIN-MAINTAIN trial showed that patients switching from injectable GLP-1 drugs (Wegovy or Zepbound) to orforglipron maintained their weight loss — average difference of only 0.9 kg. Supports orforglipron as a viable transition from injection to pill.