Compound family

GLP-1 and incretin agonists

In one sentenceThe obesity and diabetes drugs. The best-evidenced compounds on this site, and the only family with cardiovascular-outcome trials behind it.
Compounds18
Best gradeA Semaglutide
Approved medicines9 of 18
Prohibited in sport8 of 18

What this family is

These compounds mimic gut hormones released after a meal — GLP-1 first, then GIP, glucagon and amylin in the newer molecules — to slow stomach emptying, reduce appetite and improve the insulin response. Exenatide, a copy of a lizard-venom peptide, opened the class in 2005; liraglutide made it a once-daily analogue of the human hormone; dulaglutide and semaglutide made it weekly; tirzepatide added a second receptor and beat semaglutide in a direct trial. The pipeline now holds triple agonists, GLP-1/glucagon dual agonists, amylin partners (CagriSema, eloralintide, amycretin, petrelintide), a once-monthly antibody conjugate that blocks GIP rather than activating it (maridebart cafraglutide), a Chinese biased agonist with a published phase 3 (ecnoglutide) and the first oral small molecule. The amylin idea is older than it looks: pramlintide, approved in the US in 2005, proved the pathway with three mealtime injections a day, twenty years before cagrilintide made it weekly.

The evidence runs from liraglutide's 8% weight loss at 56 weeks to semaglutide's roughly 15% at 68 weeks and tirzepatide's 20% or more at 72. The cardiovascular-outcome trials separate the members: liraglutide, semaglutide and dulaglutide each reduced major events in type 2 diabetes, exenatide and lixisenatide did not, and semaglutide is the only member with such a trial in obesity without diabetes — a 20% relative reduction across 17,604 people. Grades separate cleanly by stage — A for approved medicines with outcome data, B where a phase 3 exists but the drug is unapproved or the result unreplicated, C for early-phase results however large the number.

The side-effect profile is shared: nausea, diarrhoea, vomiting and constipation concentrated in the dose-escalation months, plus rare pancreatitis and gallbladder events and a rodent-derived thyroid warning. Every approved member is prescription-only. Vials sold outside that channel are unlicensed copies, and weight-loss injectables are the focus of active enforcement in the UK. Exenatide has one more result worth knowing: its phase 3 trial as a Parkinson's disease treatment was negative — while lixisenatide, a short-acting cousin, slowed motor decline in a 156-person phase 2.

Grade counts across the family: 9 × A · 6 × B · 3 × C · 0 × D. The best grade here, A, means established in humans. How LYO grades →

The compounds, graded

Every member with its best-supported outcome grade, human-trial count and regulatory status. Each opens the full evidence page.

Semaglutide

A

GLP-1 receptor agonist. Among the most-studied molecules of the decade; approved for diabetes and obesity.

Human trials30+ RCTs
StatusApproved (Rx)

Tirzepatide

A

Dual GIP / GLP-1 agonist. Approved; beat semaglutide in a direct head-to-head trial.

Human trials15+ RCTs
StatusApproved (Rx)

Liraglutide

A

First-generation daily GLP-1 receptor agonist. Approved for diabetes and obesity; generics arriving.

Human trials20+ RCTs
StatusApproved (Saxenda, Victoza)

Dulaglutide

A

Once-weekly GLP-1 medicine approved since 2014. A cardiovascular-outcomes trial in nearly 10,000 people; weight loss well below the newer drugs.

Human trialsREWIND (n=9,901) + AWARD programme
StatusApproved (Rx)

Exenatide

A

The first GLP-1 medicine, from lizard venom, approved in 2005. Neutral in its cardiovascular trial; negative as a Parkinson's treatment.

Human trialsEXSCEL (n=14,752) + DURATION programme + Parkinson's phase 3
StatusApproved (Rx)

Retatrutide

B

Triple GIP / GLP-1 / glucagon agonist. Two phase 3 obesity trials and a phase 3 diabetes trial are published; not approved anywhere.

Human trials3 phase 3 RCTs published (n=2,339; n=1,152; n=537); 2 phase 3 topline
StatusInvestigational

Mazdutide

A

GLP-1/glucagon dual agonist. Approved in China for obesity and type 2 diabetes; phase 2 elsewhere.

Human trials3 phase 3 RCTs
StatusApproved in China only

Survodutide

B

GLP-1/glucagon dual agonist. Phase 3 published for obesity and liver disease; not yet approved.

Human trials2 phase 3 RCTs published (n=725; n=752)
StatusInvestigational

Orforglipron

A

The first oral small-molecule GLP-1 agonist, approved in the US for weight management in April 2026. A pill, not an injection — and not a peptide.

Human trialsPhase 3 programme published
StatusApproved (Rx) — United States

Cagrilintide

B

Long-acting amylin analogue. Strong phase 3 data in combination with semaglutide; not yet approved.

Human trialsPhase 3 published
StatusInvestigational

CagriSema

B

Cagrilintide and semaglutide in one pen. Two published phase 3 trials: 20.4% weight loss at 68 weeks — less than the company had hoped, more than either drug alone.

Human trials2 phase 3 RCTs published (n=3,417; n=1,206); 2 further phase 3 topline (Sep 2026)
StatusInvestigational (filed)

Amycretin

C

A GLP-1 and amylin agonist in one molecule, now named zenagamtide. The largest early-phase weight loss yet reported — in 125 people; two phase 2 diabetes trials published since.

Human trials1 phase 1b/2a RCT (n=125); 2 phase 2 RCTs in type 2 diabetes
StatusInvestigational (early phase)

Eloralintide

C

Lilly's selective amylin agonist. A published 48-week phase 2 found up to 20% weight loss with fatigue, not nausea, as the signature side effect.

Human trials1 phase 2 RCT published (n=263); 1 phase 2b topline with tirzepatide (n=367); phase 3 running
StatusInvestigational (phase 3)

Maridebart cafraglutide

B

Amgen's once-monthly antibody with two GLP-1 peptides attached. Up to 16% weight loss at 52 weeks in a published phase 2, with a GIP-blocking twist.

Human trials1 phase 2 RCT (n=592); phase 3 running
StatusInvestigational (phase 3)

Ecnoglutide

B

A Chinese once-weekly GLP-1 analogue with a published phase 3: 13.2% weight loss at 40 weeks. Approved nowhere outside China's review process.

Human trials3 phase 3 RCTs published (obesity n=664; two in diabetes)
StatusInvestigational (phase 3 published)

Petrelintide

C

Zealand and Roche's weekly amylin analogue. A published phase 2: 8–10% weight loss at 28 weeks in 493 adults, with nausea in one in five. Phase 3 started in September 2026.

Human trials1 phase 2 RCT (n=493) and 2 phase 1 RCTs published; phase 3 running
StatusInvestigational (phase 3)

Lixisenatide

A

A once-daily GLP-1 medicine with a neutral heart trial and one unexpected result: slower motor decline in early Parkinson's disease, in a 156-person phase 2.

Human trialsGetGoal programme; ELIXA (n=6,068); LIXIPARK (n=156)
StatusApproved (Rx)

Pramlintide

A

The first amylin drug, approved in the US in 2005 for diabetes. Modest weight loss in trials — and the ancestor of cagrilintide.

Human trialsApproval programme + 12-month obesity RCT (n=411)
StatusApproved (Rx, US only)

Comparisons

Questions

Is tirzepatide a GLP-1 agonist?
It activates both the GIP and the GLP-1 receptor, so strictly it is a dual incretin agonist. It is grouped with the class because it is prescribed for the same indications and shares the side-effect profile — and because it beat semaglutide head-to-head, which is the comparison people ask about.
Which of these has the strongest evidence?
Semaglutide, on volume and range: 30-plus randomised trials and the SELECT cardiovascular-outcomes trial. Tirzepatide is close on weight loss, with larger effect sizes, and has a completed outcomes trial in type 2 diabetes. Dulaglutide's REWIND trial covered the broadest population — nearly 10,000 people, most without prior heart disease.
Which GLP-1 drug came first?
Exenatide, in 2005 — a synthetic copy of exendin-4 from Gila-monster venom. Liraglutide followed in 2009 as the first analogue of the human hormone. Both are still approved and both have been overtaken by the weekly drugs.
Are all of these peptides?
All but one. Orforglipron is a small molecule — that is why it survives digestion and works as a tablet. It is included because it acts on the same receptor and competes for the same use.
What is CagriSema?
A combination of cagrilintide, an amylin analogue, with semaglutide. In the published 3,417-person REDEFINE 1 trial it produced 20.4% weight loss at 68 weeks on the intention-to-treat analysis (22.7% in the company's on-treatment figure). It is not yet approved.
Why is pramlintide in this family?
It is an amylin analogue, not a GLP-1 drug, but amylin is the other satiety hormone released with a meal and the family covers both. Pramlintide is the original; cagrilintide, eloralintide and amycretin are its weekly descendants.
Is MariTide a peptide?
Partly — two GLP-1 peptides attached to an antibody that blocks the GIP receptor, injected monthly. It is grouped here because the pharmacology is incretin and because it is one of the most-searched names in the category.

Written and maintained by LYO Research — how pages are written and checked. Reviewed 23 September 2026. Grades count human evidence only. Not medical advice. Correct this page →