GLP-1 Medications Available Now

Receptors: GLP-1GIPglucagonamylinNPY2UCN2 −GIP = antagonistStage: filled = reached, dark = currentBeyond weight loss: ✓ benefit ~ early signal ⚠ harm · untested
semaglutide Ozempic (injectable, T2D), Wegovy (injectable, obesity, 2.4 mg), Wegovy HD (injectable, obesity, 7.2 mg), Wegovy pill (oral semaglutide, obesity), Rybelsus (oral, T2D)18.7% mean weight change72 wk · obesity, no T2D · treatment-policy · raw change
Stage✓ Approved
TargetsGLP-1 receptor agonist
Maker
Routeinjection (weekly); oral daily (Rybelsus for T2D, Wegovy pill for obesity)
Indicationsapproved for type 2 diabetes, obesity, cardiovascular risk reduction, chronic kidney disease in type 2 diabetes (Ozempic, Jan 2025), MASH (noncirrhotic, moderate-to-advanced fibrosis, Aug 2025)
Efficacy18.7% mean weight loss at 72 wks on Wegovy HD 7.2 mg vs 3.9% placebo (STEP UP, treatment-policy estimand — the coprimary endpoint as published). Novo's press release led with 20.7%, which is the trial-product estimand. The standard 2.4 mg injection gives ~15% (STEP 1). SELECT showed 20% lower MACE. source
  • Wegovy HD (injectable, obesity, 7.2 mg): 18.7% at 72 wks vs 3.9% placebo (treatment-policy estimand; 20.7% on the trial-product estimand). 13.2% in the type 2 diabetes population. FDA-approved 19 Mar 2026.
  • Wegovy (injectable, obesity, 2.4 mg): ~15% mean weight loss (STEP 1)
  • Wegovy pill (oral, obesity, 25 mg): 16.6% adherent / 13.6% overall (OASIS 4)
  • Ozempic (injectable, T2D): diabetes dose, meaningfully less weight loss than Wegovy
  • Rybelsus (oral, T2D, up to 14 mg): diabetes dose, ~3-4% (not a weight-loss dose)
Beyond weight loss
  • ✓ Cardiovascular: 20% lower MACE (CV death/MI/stroke) (SELECT, NEJM 2023 · source)
  • ✓ Heart failure (HFpEF): In obesity-related HFpEF (no diabetes, n=529), KCCQ symptom score +16.6 vs +8.7 placebo (diff +7.8), 6-min walk +20.3 m, win ratio 1.72 — symptom benefit beyond what diuretics alone deliver. (STEP-HFpEF, NEJM 2023 · source)
  • ~ Cancer (class-level signal): Across GLP-1 RA users (not semaglutide-specific): 41% lower incidence of obesity-associated cancers in obese, nondiabetic adults (HR 0.59, 95% CI 0.53-0.67; target trial emulation, n=161,798 matched). Observational — authors note prospective trials needed to confirm causality. (Hsu et al., Annals of Oncology 2026 (PMID 42252247) · source)
  • ✓ Knee osteoarthritis: WOMAC pain fell 41.7 points from a baseline of 70.9 vs 27.5 on placebo — a between-group difference of 14.1 points. Worth knowing that the placebo arm also got diet and activity counselling and captured about two thirds of the total pain relief, so this is not a drug-alone effect. (STEP 9, NEJM 2024, n=407, 68 wks · source)
  • ~ Alcohol use disorder: Reduced craving + heavy drinking at low dose (JAMA Psychiatry 2025 (Phase 2, n=48) · source)
  • ~ Bone: In a small phase 2 trial (n=64, mostly postmenopausal women) at the 1.0 mg DIABETES dose — not the 2.4 mg obesity dose — bone mineral density fell at the lumbar spine and total hip relative to placebo, with no difference at the femoral neck. Read it carefully: the trial's primary endpoint (a bone-formation marker) was negative, the BMD findings are secondary, and the authors themselves suggest the accompanying weight loss may explain it rather than the drug. (Phase 2, eClinicalMedicine 2024, n=64, negative primary endpoint · source)
  • ~ Bone / falls (older adults, real-world): In adults ≥65 with T2D + overweight/obesity (TriNetX retrospective cohort, 1:1 matched vs DPP-4 inhibitors, n=27,896), 1-yr femoral fracture was lower (0.3% vs 0.5%, HR 0.49) and falls were lower (3.6% vs 5.4%, HR 0.66); fracture benefit larger at BMI ≥30. Observational, and the comparator is another diabetes drug (DPP-4), not placebo — so this nuances but doesn't overturn the RCT-measured BMD/lean-mass loss. The mechanistic bone-density loss and the net fall/fracture outcome are measuring different things. (Chen et al., Osteoporos Int 2026 (PMID 42435064) · source)
Access & priceSelf-pay: NovoCare self-pay: $349/mo for Wegovy 0.25-2.4 mg, $399/mo for Wegovy HD 7.2 mg, $149/mo for the Wegovy pill (the 4 mg pill rises to $199 after 31 Aug 2026). · Medicare GLP-1 Bridge covers both the Wegovy pen and the pill at ~$50/mo from 1 Jul 2026 through 31 Dec 2027. Widely covered for type 2 diabetes; obesity coverage varies. · compare price (GoodRx)
Key trials
  • SELECT (Ph 3, CV outcomes (obesity, no diabetes)) — 20% reduction in CV death / MI / stroke across 17,600+ patients. source
  • STEP UP (Ph 3, obesity) — Pivotal trial for the 7.2 mg high dose: 18.7% mean weight loss at 72 wks vs 3.9% placebo on the treatment-policy estimand (20.7% vs 2.4% on the trial-product estimand, which is the figure Novo's press release led with). In the separate type 2 diabetes population the treatment-policy result was 13.2%. Basis for the 19 Mar 2026 FDA approval of Wegovy HD. source
Papers
On DSD
My takeThe OG that really kicked of the revolution. Not the most effective anymore, but most widely studied. Begining to come of patent in some countries.
tirzepatide Mounjaro (T2D), Zepbound (obesity, OSA)20.9% mean weight change72 wk · obesity, no T2D · treatment-regimen · raw change
Stage✓ Approved
TargetsGIPGLP-1 dual agonist
Maker
Routeinjection (weekly)
Indicationsapproved for type 2 diabetes, obesity, obstructive sleep apnea; investigating type 1 diabetes with obesity
Efficacy20.9% mean weight loss at 72 wks on 15 mg vs 3.1% placebo (SURMOUNT-1, treatment-regimen estimand; 22.5% vs 2.4% on the efficacy estimand) source
Beyond weight loss
  • ✓ Sleep apnea: Up to 51.5% met OSA disease-resolution criteria — FDA-approved for OSA (SURMOUNT-OSA, NEJM 2024 · source)
  • ✓ Diabetes (A1c): Stronger glycemic control than semaglutide head-to-head (SURPASS-2)
  • ~ Heart failure (HFpEF): In HFpEF with obesity (n=731, median follow-up 104 wks) tirzepatide reduced the composite of cardiovascular death or worsening heart-failure events. KCCQ symptom score at 52 wks improved 19.5 points vs 12.7 on placebo, a difference of 6.9. The regulatory path stalled: Lilly submitted for HFpEF with obesity in Nov 2024 then withdrew the US application, disclosed in its Q1 2025 filing on 1 May 2025, after the FDA asked for a confirmatory trial. Tirzepatide is not approved for heart failure and no confirmatory trial is registered. (SUMMIT, NEJM 2025 · source)
  • ⚠ Bone: ~25% of weight lost is lean mass; retrospective signal of higher fracture risk vs other GLP-1s (RCT + retrospective cohort)
  • ~ Bone / falls (older adults, real-world): In adults ≥65 with T2D + overweight/obesity (TriNetX retrospective cohort, 1:1 matched vs DPP-4 inhibitors, n=12,808), 1-yr femoral fracture was lower (0.2% vs 0.4%, HR 0.45) and falls were lower (3.6% vs 5.7%, HR 0.66). Observational, comparator is DPP-4 not placebo. Sits alongside the lean-mass loss and the earlier retrospective higher-fracture signal — the fracture picture is genuinely mixed, and weight loss itself lowers fall/joint load. (Chen et al., Osteoporos Int 2026 (PMID 42435064) · source)
Access & priceSelf-pay: LillyDirect self-pay: $299/mo at 2.5 mg, $399 at 5 mg and $449 at 7.5-15 mg (Feb 2026). The Zepbound KwikPen is now available self-pay alongside the single-dose vials. · Medicare GLP-1 Bridge covers the Zepbound KwikPen at ~$50/mo from Jul 2026. Covered for type 2 diabetes; obesity and sleep-apnea coverage varies. · compare price (GoodRx)
Key trials
  • SURMOUNT-OSA (Ph 3, obstructive sleep apnea) — Up to 51.5% of participants met criteria for OSA disease resolution. source
  • SURMOUNT-MAINTAIN (Ph 3, weight maintenance) — Published in The Lancet 12 May 2026. After 60 wks of open-label tirzepatide, 378 adults were randomised for 52 more: at week 112, -21.9% staying at max tolerated dose, -16.6% stepping down to 5 mg, -9.9% on placebo. Regain of half the lost weight: 8% vs 25% vs 67%. source
Papers
On DSD
My takeThe current king of appetite suppression. I have been on this since November 2024 and lost 170lbs. My personal favorite.
orforglipron Foundayo11.2% mean weight change72 wk · obesity, no T2D · treatment-regimen · raw change
Stage✓ Approved
TargetsGLP-1 receptor agonist (oral, non-peptide small molecule)
Maker
Routeoral (daily, no food/water restriction)
Indicationsapproved for obesity / weight management; investigating type 2 diabetes
Efficacy~11.2% mean weight loss at 72 wks (ATTAIN-1, treatment-regimen estimand; 12.4% efficacy estimand) — more modest than injectable GLP-1s. Approved dose is 17.2 mg once daily; the 36 mg figure quoted from the trial is the equivalent capsule, not the tablet you are prescribed. source
Beyond weight loss
  • ✓ Type 2 diabetes: ACHIEVE-3 head-to-head (Lancet 2026, n=1,698): superior to oral semaglutide — 9.2% vs 5.3% weight loss at top doses (~73.6% greater relative loss) and greater A1C reduction over 52 wks. Broader ACHIEVE program (incl. ACHIEVE-2 vs dapagliflozin, ACHIEVE-5 on insulin) supports a T2D filing. ACHIEVE-5 (insulin add-on) published in JAMA and ACHIEVE-2 (vs dapagliflozin) in The Lancet, June 2026. (ACHIEVE-3, Lancet 2026 (ADA 2026) · source)
  • ✓ Menopause (women): Worked at every menopausal stage. In ATTAIN-1 (obesity without diabetes, highest dose): pre-menopausal -12.8% (-28.0 lb), peri-menopausal -14.4% (-30.4 lb), post-menopausal -14.1%. ATTAIN-2 (the type 2 diabetes population) ran lower and in a different order: pre -11.3%, peri -8.9%, post -13.6%. More than 1,500 women across both trials. (ATTAIN-1/ATTAIN-2 post-hoc, presented ADA 2026 (7 Jun 2026) · source)
  • · Everything else: Largely untested — newest molecule; CV / OSA / OA / addiction effects not yet studied. Do NOT assume semaglutide's benefits transfer. (no data yet)
Access & priceSelf-pay: LillyDirect self-pay on the Foundayo Self Pay Journey Program: $149/mo at the 0.8 mg starting dose, $199 at 2.5 mg, and $299 at 5.5 mg and above — the top two doses hold that $299 as long as you refill within 45 days. With commercial insurance that covers Foundayo, as little as $25/mo. · Medicare GLP-1 Bridge since 1 Jul 2026 (~$50/mo, eligibility applies); commercial coverage varies, with a $25/mo copay program for those covered. · UK: launched 24 Aug 2026 — first European market, two weeks after MHRA authorisation (10 Aug, first GLP-1 tablet approved in Europe for weight management; the UK label also covers type 2 diabetes, an indication still pending in the US). Private prescription only, running £129–£179/mo depending on dose at launch. NICE's NHS-funding decision is expected November 2026, so NHS prescribing is unlikely before 2027. · compare price (GoodRx)
Key trials
  • ATTAIN-MAINTAIN (Ph 3, weight maintenance after injectable) — Maintained weight loss after switching from Wegovy/Zepbound to oral orforglipron. source
  • ACHIEVE-3 (Ph 3, type 2 diabetes (head-to-head vs oral semaglutide)) — n=1,698; orforglipron superior to oral semaglutide on A1C and weight (9.2% vs 5.3% at top doses, ~73.6% greater relative weight loss) over 52 wks. Published in The Lancet. source
  • ACHIEVE-2 (Ph 3, type 2 diabetes (head-to-head vs dapagliflozin)) — Open-label non-inferiority vs dapagliflozin in T2D on metformin: A1C lowered by up to 1.7% vs 0.8% with dapagliflozin at 40 wks. Published in The Lancet (8 Jun 2026). source
  • ACHIEVE-5 (Ph 3, type 2 diabetes (add-on to insulin glargine)) — n=546, 40 wks, add-on to titrated insulin glargine (+/- metformin/SGLT2i): HbA1c -1.88% (12 mg) / -1.82% (36 mg) / -1.58% (3 mg) vs -0.79% placebo (difference up to -1.08%). Up to 70.5% reached HbA1c <7% vs 24.7% placebo. Weight -5.4% (36 mg) vs +0.2% placebo. No increase in hypoglycemia. Published in JAMA. source
  • ACHIEVE-4 (Ph 3, type 2 diabetes (longest orforglipron study)) — Longest Phase 3 orforglipron study to date; reaffirmed cardiovascular and overall safety profile with consistent cardiometabolic improvements. source
Papers
On DSD
My takeVery interesting entry because it avoids the needles and the onerous Wegovy pill protocol.
The pipeline moves fast. I keep this current.
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