Metabolic peptides

GLP Peptides

GLP stands for glucagon-like peptide. GLP-1 and GLP-2 are hormones made by L-cells in your gut lining when you eat[1][2]. Drug developers have built longer-lasting versions that copy these signals. Some of them have large effects on blood sugar, appetite, and body weight[3][4].

  1. You eatfood reaches the gut
  2. L-cells release GLP-1 and GLP-2gut hormones[1][2]
  3. GLP-1 → pancreas: more insulin, less glucagon[1]brain: you feel full sooner and eat less[1]stomach: food leaves the stomach more slowly[1]
    GLP-2 → gut lining: growth and upkeep of the lining[5][2]

What GLP-1 does

GLP-1 is released by L-cells in your intestine after you eat[1]. It has two main jobs. First, it helps the pancreas release insulin and hold back glucagon, which keeps blood sugar from spiking after meals. Second, it signals fullness, so you eat less[1]. It also slows how fast food leaves your stomach, which helps you feel full longer[1].

Natural GLP-1 doesn't last long. An enzyme called DPP-4 breaks it down, and its half-life in the blood is only about 1.5 to 2 minutes in people[2][1]. Drug versions are built to resist this breakdown. Semaglutide and tirzepatide last long enough to be injected once a week[6][7].

The GLP-2 layer

GLP-2 is released along with GLP-1, but it acts mainly on the gut. It helps the intestinal lining grow and stay intact[5][2]. A longer-lasting GLP-2 drug, teduglutide, is FDA approved for short bowel syndrome, a condition in which the gut can't absorb enough nutrients[2]. It was also tested in a small trial in Crohn's disease, with mixed results[8].

GLP peptide comparison

Drugs and research compounds

Semaglutide and tirzepatide are FDA approved as prescription drugs[9][7]. Compounded versions and products sold "for research purposes" are not FDA approved[10].

GLP-1 only

Semaglutide
FDA approved

It acts on one target: GLP-1. It is a long-acting GLP-1 drug[9][6].

Main research areas
Type 2 diabetes, obesity, heart attack and stroke risk, MASH (a fatty liver disease once called NASH)[9][6]
Key point
Cardiovascular outcome data; once-weekly dosing[6]; a higher 7.2 mg weekly dose was approved in 2026[11]
What studies have used (not a recommendation)
0.25 to 2.4 mg/week subcutaneous[3][6]

GLP-1 plus one target

Tirzepatide, often called GLP-2
FDA approved

It isn't the gut hormone GLP-2. It acts on two targets: GLP-1 and GIP[12][7].

Main research areas
Type 2 diabetes, obesity, obstructive sleep apnea[12][7]
Key point
In a 72-week head-to-head trial, people lost about 20% of body weight on tirzepatide vs. about 14% on semaglutide[13]; in a 72-week obesity trial, every planned heart and metabolic measure improved[4]
What studies have used (not a recommendation)
2.5 to 15 mg/week subcutaneous[7][4]

GLP-1 plus two targets

Retatrutide, often called GLP-3
In clinical trials, not FDA approved

There's no GLP-3 hormone. It acts on three targets at once: GLP-1, GIP, and glucagon. It is still in clinical trials and is not FDA approved[14][10].

Main research areas
Obesity, fatty liver disease, knee arthritis pain, sleep apnea[15][16]
Key point
The glucagon part raised energy use in animal studies[17]; average weight loss was about 24% at 48 weeks in phase 2 and 25% at 80 weeks in phase 3 on the 12 mg dose[14][15]; not FDA approved[10]
What studies have used (not a recommendation)
1 to 12 mg/week subcutaneous (Phase 2/3 trials)[14][15][18]

For education only

Why a second or third target matters

Each added receptor works on a different part of metabolism. GLP-1 action lowers appetite and helps insulin release[1]. GIP (glucose-dependent insulinotropic polypeptide) is another gut hormone that boosts insulin release after meals[2]. In a head-to-head trial, tirzepatide (GLP-1 plus one target, GIP) led to more weight loss than semaglutide (GLP-1 only)[13]. Glucagon receptor action raised energy use in animal studies[17]. Retatrutide (GLP-1 plus two targets, GIP and glucagon) is being studied because it combines all three[14]. In mice, its weight loss came from eating less (the GLP-1 and GIP effects) plus burning more energy (the glucagon effect)[17]. In people, phase 3 results are still coming in, and it is not approved[15][10].

Sources

The numbers in brackets on this page point to the sources below. Each one links to the original study, drug label, or government page.

  1. 1.

    Holst JJ (2007). The physiology of glucagon-like peptide 1 (opens in a new tab). Physiological Reviews. Back to citation

  2. 2.

    Drucker DJ, et al. (2017). Discovery, characterization, and clinical development of the glucagon-like peptides (opens in a new tab). The Journal of Clinical Investigation. Back to citation

  3. 3.

    Wilding JPH, et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity (opens in a new tab). The New England Journal of Medicine. Back to citation

  4. 4.

    Jastreboff AM, et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity (opens in a new tab). The New England Journal of Medicine. Back to citation

  5. 5.

    Estall JL, Drucker DJ (2006). Glucagon-like Peptide-2 (opens in a new tab). Annual Review of Nutrition. Back to citation

  6. 6.

    U.S. Food and Drug Administration (2026). Semaglutide injection and tablets for weight management: prescribing information (opens in a new tab). Drugs@FDA. Back to citation

  7. 7.

    U.S. Food and Drug Administration (2025). Tirzepatide injection for weight reduction and sleep apnea: prescribing information (opens in a new tab). Drugs@FDA. Back to citation

  8. 8.

    Buchman AL, et al. (2010). Teduglutide, a novel mucosally active analog of glucagon-like peptide-2 (GLP-2) for the treatment of moderate to severe Crohn's disease (opens in a new tab). Inflammatory Bowel Diseases. Back to citation

  9. 9.

    U.S. Food and Drug Administration (2026). Semaglutide injection for type 2 diabetes: prescribing information (opens in a new tab). Drugs@FDA. Back to citation

  10. 10.

    U.S. Food and Drug Administration (2026). FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss (opens in a new tab). U.S. Food and Drug Administration. Back to citation

  11. 11.

    U.S. Food and Drug Administration (2026). FDA Approves Fourth Product Under National Priority Voucher Program, Higher Dose Semaglutide (opens in a new tab). U.S. Food and Drug Administration. Back to citation

  12. 12.

    U.S. Food and Drug Administration (2026). Tirzepatide injection for type 2 diabetes: prescribing information (opens in a new tab). Drugs@FDA. Back to citation

  13. 13.

    Aronne LJ, et al. (2025). Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (opens in a new tab). The New England Journal of Medicine. Back to citation

  14. 14.

    Jastreboff AM, et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial (opens in a new tab). The New England Journal of Medicine. Back to citation

  15. 15.

    Jastreboff AM, et al. (2026). Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (opens in a new tab). The New England Journal of Medicine. Back to citation

  16. 16.

    Sanyal AJ, et al. (2024). Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial (opens in a new tab). Nature Medicine. Back to citation

  17. 17.

    Coskun T, et al. (2022). LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept (opens in a new tab). Cell Metabolism. Back to citation

  18. 18.

    U.S. National Library of Medicine (2026). A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight (TRIUMPH-1) (opens in a new tab). ClinicalTrials.gov. Back to citation