GLP-1 Medications Available Now

Receptors: GLP-1GIPglucagonamylin −GIP = antagonistStage: filled = reached, dark = currentBeyond weight loss: ✓ benefit ~ early signal ⚠ harm · untested
semaglutide Ozempic (injectable, T2D), Wegovy (injectable, obesity), Wegovy pill (oral semaglutide, obesity), Rybelsus (oral, T2D)15% weight loss
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; investigating MASH, oral obesity dose
Efficacy~15% mean weight loss (STEP 1, Wegovy 2.4 mg); 20% lower MACE in SELECT source
  • 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 −59% vs −39%; benefit exceeded what weight loss alone predicts (STEP-9, NEJM 2024)
  • ~ Alcohol use disorder: Reduced craving + heavy drinking at low dose (JAMA Psychiatry 2025 (Phase 2, n=48) · source)
  • ⚠ Bone: Hip BMD −2.6% / spine −2.1% over 52 wks; lean-mass loss (RCT in high-fracture-risk adults)
  • ~ 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 program · Widely covered for T2D; 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
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)21% weight loss
Stage✓ Approved
TargetsGIPGLP-1 dual agonist
Maker
Routeinjection (weekly)
Indicationsapproved for type 2 diabetes, obesity, obstructive sleep apnea; investigating dose maintenance (SURMOUNT-MAINTAIN)
Efficacy~21% mean weight loss (SURMOUNT-1, 15 mg) 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 + obesity (n=731), reduced the composite of CV death or worsening heart-failure events and improved KCCQ symptom score (+24.8 vs +15.0 placebo), 6-min walk, and hsCRP over 1 yr. (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 vials · Covered for T2D; obesity/OSA 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
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% weight loss
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 (ATTAIN-1, 36 mg, 72 wks) — more modest than injectable GLP-1s 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 a post-hoc analysis of >1,500 women across ATTAIN-1 and ATTAIN-2 (highest dose): pre-menopausal -12.8% (-28.0 lb), peri-menopausal -14.4% (-30.4 lb), post-menopausal -14.1% (-28.2 lb). Up to 51.5% of ATTAIN-1 women reached >=15% weight loss; waist circumference down up to 4.9 in (12.5 cm) at 72 wks. (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 (~$149-299/mo self-pay) · Medicare GLP-1 Bridge from Jul 1, 2026 (~$50/mo, eligibility applies) · 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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