Which pipeline drug shows the most weight loss?

Retatrutide, with 28.3% at 80 weeks on 12 mg in TRIUMPH-1 and up to 30.3% at 104 weeks in a higher-BMI extension. It is not approved by any major regulator, so there is no way to obtain it outside a clinical trial.

Can these percentages be ranked directly?

Not reliably. Trial durations run from 48 to 104 weeks, populations differ substantially, placebo arms lost between 0.5% and 3.9%, and some figures are efficacy estimands while others are treatment-regimen estimands. Ranking them as if they were one experiment overstates what is known.

When will the unapproved ones become available?

Approval timing is a regulatory decision and cannot be predicted from trial results. This board states current status only, as verified on 23 August 2026.

The Next-Generation GLP-1 Pipeline

What this page establishes

Retatrutide (GIP/GLP-1/glucagon, Lilly): up to 28.3% at 80 weeks, TRIUMPH-1; 30.3% at 104 weeks in a higher-BMI extension. Not approved.
CagriSema (amylin + GLP-1, Novo Nordisk): 22.7% at 68 weeks, REDEFINE-1, n=3,417.
Survodutide (GLP-1/glucagon, Boehringer Ingelheim): 16.6% at 76 weeks, SYNCHRONIZE-1, n=725.
Orforglipron (Foundayo, oral small-molecule GLP-1, Lilly): FDA-approved 1 April 2026; 12.4% at 72 weeks on the efficacy estimand.

Quick answers

Which pipeline drug shows the most weight loss?
Retatrutide, with 28.3% at 80 weeks on 12 mg in TRIUMPH-1 and up to 30.3% at 104 weeks in a higher-BMI extension.
Read the full answer
It is not approved by any major regulator, so there is no way to obtain it outside a clinical trial.
Can these percentages be ranked directly?
Not reliably. Trial durations run from 48 to 104 weeks, populations differ substantially, placebo arms lost between 0.5% and 3.9%, and some figures are efficacy estimands while others are treatment-regimen estimands.
Read the full answer
Ranking them as if they were one experiment overstates what is known.
When will the unapproved ones become available?
Approval timing is a regulatory decision and cannot be predicted from trial results. This board states current status only, as verified on 23 August 2026.
Read the full answer

This page is a board, not an argument. Each candidate gets its mechanism, sponsor, best published phase 3 number with the trial and duration attached, and its regulatory position by jurisdiction. It exists so that the compound pages do not each have to carry a status paragraph that goes stale. Last reviewed 23 August 2026. Anything on this page can change within a quarter, and three of the statuses below are the kind that do.

How to read this board

Every number carries a trial name, a dose where relevant and a duration. A percentage without those is not checkable and does not belong here.

Approved always carries a jurisdiction. A drug approved in China is not approved in the United States, and neither status implies anything about the other. Phase 3 with reported results means the trial finished and the numbers are public, which is not the same as available.

Approved, by jurisdiction

Semaglutide (GLP-1, Novo Nordisk). FDA and EMA approved for weight management and type 2 diabetes. 14.9% at 68 weeks on 2.4 mg in STEP 1 (n=1,961). Oral 25 mg approved 22 December 2025, 16.6% at 64 weeks under adherence in OASIS 4 (n=307).
Tirzepatide (GIP/GLP-1, Eli Lilly). FDA approved as Mounjaro and Zepbound. 22.5% at 72 weeks on 15 mg in SURMOUNT-1 (n=2,539) versus 2.4% placebo.
Orforglipron (Foundayo, oral small-molecule GLP-1, Eli Lilly). FDA approved 1 April 2026. 12.4% at 72 weeks on 36 mg, efficacy estimand, in ATTAIN-1; 9.6% on the treatment-regimen estimand.
Mazdutide (GLP-1/glucagon, Innovent Biologics). Approved by China's NMPA for weight management and for type 2 diabetes. Not FDA- or EMA-approved. About 14.8% at 48 weeks on 6 mg in GLORY-1 (n=610), about 20% on 9 mg in a further phase 3.
Tesamorelin (GHRH analogue). FDA approved 10 November 2010, for excess visceral abdominal fat in adults with HIV and lipodystrophy only. Not an obesity drug and not studied as one.

Phase 3 with reported results, not approved

Retatrutide (GIP/GLP-1/glucagon, Eli Lilly). 28.3% at 80 weeks on 12 mg in TRIUMPH-1 (n=2,339), 45.3% losing 30% or more. Up to 30.3% at 104 weeks in a BMI 35+ extension. TRIUMPH-2 and TRIUMPH-3 reported up to 22.6%.
CagriSema (amylin + GLP-1, Novo Nordisk). 22.7% at 68 weeks in REDEFINE-1 (n=3,417), 20.4% on the treatment-policy estimand. Also studied in type 2 diabetes in REDEFINE-2. Published in NEJM.
Cagrilintide monotherapy (amylin, Novo Nordisk). 11.8% at 68 weeks in the REDEFINE-1 monotherapy arm, below semaglutide in the same trial.
Survodutide (GLP-1/glucagon, Boehringer Ingelheim). Up to 16.6% at 76 weeks in SYNCHRONIZE-1 (n=725) versus 3.2% placebo. Up to 84.2% achieved a 30% or greater relative reduction in liver fat. Separate SYNCHRONIZE-MASLD programme.

Reported results is not availability Retatrutide, CagriSema, cagrilintide and survodutide have no legal human-use route in the US or EU as of 23 August 2026. All four are sold online as research chemicals. Those products are not the trial drug and are not covered by any regulator.

The mechanism classes, briefly

Mono-agonist. GLP-1 receptor only. Semaglutide, orforglipron. Appetite suppression and slowed gastric emptying.
Dual incretin. GIP plus GLP-1. Tirzepatide. Adding GIP raised the ceiling on weight loss relative to GLP-1 alone.
GLP-1 plus glucagon. Survodutide, mazdutide. Glucagon-receptor agonism is associated with increased energy expenditure and with liver-fat effects.
Triple agonist. GIP plus GLP-1 plus glucagon. Retatrutide. Currently the largest published weight-loss numbers of any obesity drug.
Amylin. Cagrilintide, and CagriSema as an amylin-GLP-1 combination. A satiety pathway separate from the incretins, which is the argument for combining rather than escalating.

What these numbers do not let you do

They do not let you rank the drugs. Trial durations on this page run from 48 to 104 weeks. Populations differ, with GLORY-1 enrolling Chinese adults only and most obesity trials excluding people with type 2 diabetes. Placebo arms lost anywhere from 0.5% to 3.9%, and the placebo response alone can shift an apparent effect size by three percentage points.

Estimands differ too, and the same trial arm can legitimately produce two numbers several points apart. Reading a table of headline percentages as a league table produces a confident ranking the evidence does not support. Only head-to-head randomised trials answer which drug is better, and most of these pairs have never been tested against each other.

Last reviewed

Reviewed 23 August 2026. Three items on this board carry the highest chance of moving: CagriSema's approval status, orforglipron's label scope following its April 2026 approval, and any first regulatory submission for retatrutide. Regulatory status should be confirmed against FDA, EMA or the relevant national regulator rather than taken from this page if the decision matters.

Not medical advice This board is educational. It contains no dosing guidance and is not a recommendation to seek or take any of these drugs. Investigational compounds have no legal human-use route. Treatment decisions belong with a licensed prescriber.

The evidence, one row per claim

Claim	Tier	Source
Retatrutide (GIP/GLP-1/glucagon, Lilly): up to 28.3% at 80 weeks, TRIUMPH-1; 30.3% at 104 weeks in a higher-BMI extension. Not approved.	established	AJMC
CagriSema (amylin + GLP-1, Novo Nordisk): 22.7% at 68 weeks, REDEFINE-1, n=3,417.	established	Novo Nordisk / NEJM
Survodutide (GLP-1/glucagon, Boehringer Ingelheim): 16.6% at 76 weeks, SYNCHRONIZE-1, n=725.	established	Boehringer Ingelheim SYNCHRONIZE-1 topline press release, 28 April 2026 (Internet Archive snapshot)
Mazdutide (GLP-1/glucagon, Innovent): approved in China; reported ~14.8% at 48 weeks on 6 mg in GLORY-1, ~20% on 9 mg in a further phase 3.	weak evidence	Patient Care Online (not confirmed against a primary source, 2026-08-23)
Orforglipron (Foundayo, oral small-molecule GLP-1, Lilly): FDA-approved 1 April 2026; 12.4% at 72 weeks on the efficacy estimand.	established	ClinicalTrials.gov posted results for ATTAIN-1 (NCT05869903), first posted 14 August 2026
Cross-trial comparison is unsafe: durations range 48-104 weeks, populations differ (Chinese-only in GLORY-1, non-diabetic in most obesity trials), and placebo responses range 0.5-3.9%.	established	The Cardiology Advisor
Semaglutide injectable: 0.25 / 0.5 / 1.0 / 1.7 / 2.4 mg weekly, 4 weeks per step, 2.4 mg maintenance; 14.9% mean loss at 68 weeks (STEP 1).	established	STEP 1
Tirzepatide: 2.5 mg initiation then 5 / 10 / 15 mg weekly maintenance; 16.0% / (10 mg intermediate) / 22.5% mean loss at 72 weeks (SURMOUNT-1).	established	Eli Lilly / NEJM
Orforglipron 36 mg gave 12.4% (efficacy estimand) / 9.6% (treatment-regimen estimand) at 72 weeks in ATTAIN-1.	established	ClinicalTrials.gov posted results for ATTAIN-1 (NCT05869903), first posted 14 August 2026

Questions people ask

Why is tesamorelin on a board of obesity drugs?

Because it is routinely marketed as one. Its actual FDA approval, from 10 November 2010, covers reduction of excess visceral abdominal fat in adults with HIV and lipodystrophy. It was not developed or studied as a treatment for obesity.

Sources

Where this comes from

Researched and edited by Thomas Prommer — biohacker, performance athlete, data enthusiast and health coach.

Every number on this page traces to a named source. There are 9 sourced claims below the fold, each with the document it came from.

Sources consulted: AJMC, Novo Nordisk / NEJM, Boehringer Ingelheim SYNCHRONIZE-1 topline press release, Patient Care Online, ClinicalTrials.gov posted results for ATTAIN-1 and 3 more.

Not clinically reviewed. This page was researched and written against primary regulatory and trial sources, and no clinician has checked it.

Sources last read 2026-08-23.

Keep reading

Educational content, reviewed 2026-08-23. Not medical advice, not a prescription, and not a substitute for a clinician who knows your history. Doses named here are label schedules or doses used in named trials, never a recommendation to you.

The Next-Generation Obesity Drug Pipeline: Who Is Where