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Weight and metabolism

Medicines such as semaglutide and tirzepatide have changed the treatment of overweight, and retatrutide is on its way. Here you can see what the studies show, how the medicines work, and how to get them through your doctor.

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Peptides in this topic

All peptides
  • RetatrutideMedicine in clinical trials

    A weekly injection from Eli Lilly that acts on three gut hormones. Large studies show substantial weight loss, and the medicine is in the last phase of clinical trials.

    Large human trials
  • SemaglutideApproved medicine

    An approved prescription medicine for type 2 diabetes and overweight. One of the best-studied peptide medicines there is.

    Large human trials
  • TirzepatideApproved medicine

    An approved prescription medicine that acts on two gut hormones. Large studies show substantial weight loss and better blood sugar.

    Large human trials
  • MOTS-cResearch compound

    A small peptide the body makes in its mitochondria. Promising in mice for metabolism and fitness, with the first studies in humans under way.

    Lab and animal studies

Why peptides matter for weight and metabolism

The body uses its own peptide hormones to control hunger, fullness and blood sugar. After a meal, the gut releases hormones such as GLP-1 and GIP, which raise insulin when blood sugar rises and help you feel full.[1] The new weight-loss medicines mimic these hormones and work for longer than the body's own. This is why peptides have become one of the most important fields in the treatment of obesity and type 2 diabetes. Read how the hormones work.

One, two or three hormones

  • Semaglutide acts on one hormone, GLP-1. In the STEP 1 study, participants lost on average 14.9 per cent of their body weight over 68 weeks, against 2.4 per cent with placebo.[2]
  • Tirzepatide acts on two hormones, GLP-1 and GIP. In SURMOUNT-1, participants lost between 15.0 and 20.9 per cent over 72 weeks, depending on the dose.[3] In a head-to-head comparison, those on tirzepatide lost 20.2 per cent, against 13.7 per cent with semaglutide.[4]
  • Retatrutide acts on three hormones, GLP-1, GIP and glucagon. In TRIUMPH-1, participants in the highest dose group lost 25.0 per cent over 80 weeks.[5]

More than weight loss

The studies also show health gains beyond weight. With semaglutide, fewer people had a heart attack or stroke or died of cardiovascular disease in the SELECT study, which followed more than 17,000 people for over three years.[6] In people with type 2 diabetes, both semaglutide and tirzepatide clearly improved long-term blood sugar.[7][8] With retatrutide, knee pain in knee osteoarthritis and breathing pauses in sleep apnoea went down, and liver fat fell markedly.[5][9]

The studies also show that continuing treatment pays off. In SURMOUNT-4, those who stayed on tirzepatide kept their weight down.[10]

A peptide the body makes itself

MOTS-c is a small peptide made in the mitochondria, the power plants of the cell. In mice, it prevented insulin resistance and weight gain on a high-fat diet.[11] In humans, the body's own production of MOTS-c rises during exercise.[12] The first studies in humans are under way.

How do I get one of these medicines?

Semaglutide and tirzepatide are approved medicines. Talk to your doctor, who will decide whether the treatment suits you. If you get a prescription, you collect the medicine from a pharmacy or order it from an approved Norwegian online pharmacy.

Questions and answers

What is the difference between semaglutide and tirzepatide?

Semaglutide acts on one gut hormone, GLP-1. Tirzepatide acts on two, GLP-1 and GIP. Both are approved and available on prescription, and in a head-to-head comparison tirzepatide gave the greater weight loss.

When will retatrutide be available?

Retatrutide is in the final phase of clinical trials, with large studies in humans. Once the studies are complete, the manufacturer can apply for approval.

How do I get one of these medicines?

Talk to your doctor. If you get a prescription, you collect the medicine from a pharmacy or order it from an approved Norwegian online pharmacy.

Sources

  1. [1]

    Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007.

    PMID 17498508DOIReview

  2. [2]

    Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021.

    PMID 33567185DOIRCT · n = 1,961 · Funding or ties: Novo Nordisk.

  3. [3]

    Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022.

    PMID 35658024DOIRCT · n = 2,539 · Funding or ties: Eli Lilly.

  4. [4]

    Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025.

    PMID 40353578DOIRCT · n = 751 · Funding or ties: Eli Lilly.

  5. [5]

    Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. 2026.

    PMID 42814954DOIRCT · n = 2,339 · Funding or ties: Eli Lilly.

  6. [6]

    Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023.

    PMID 37952131DOIRCT · n = 17,604 · Funding or ties: Novo Nordisk.

  7. [7]

    Sorli C, Harashima SI, Tsoukas GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol. 2017.

    PMID 28110911DOIRCT · n = 388 · Funding or ties: Novo Nordisk.

  8. [8]

    Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021.

    PMID 34170647DOIRCT · n = 1,879 · Funding or ties: Eli Lilly.

  9. [9]

    Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024.

    PMID 38858523DOIRCT · n = 98 · Funding or ties: Eli Lilly.

  10. [10]

    Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024.

    PMID 38078870DOIRCT · n = 670 · Funding or ties: Eli Lilly.

  11. [11]

    Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015.

    PMID 25738459DOIAnimal study

  12. [12]

    Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021.

    PMID 33473109DOIAnimal study · Funding or ties: CohBar.