Metabolic peptides are compounds that act on blood sugar, insulin, liver fat and energy use. The proven ones are GLP-1-based diabetes drugs such as semaglutide (Ozempic), tirzepatide (Mounjaro) and dulaglutide (Trulicity), which lower HbA1c and, in several cases, heart risk.[1][2][4] Mitochondrial compounds sold for metabolism, such as MOTS-c and NAD+, have little or no human evidence of benefit.[17][20]

What are metabolic peptides?

Metabolic peptides are short protein-like molecules that change how the body handles glucose, fat and energy. Most approved ones copy gut or pancreatic hormones released after meals, such as GLP-1 and amylin.[1][8]

The category also includes compounds that are not peptides at all. NAD+ is a coenzyme, orforglipron is a small-molecule pill, and SLU-PP-332 and 5-Amino-1MQ are lab-made small molecules tested only in animals.[21][22]

Browse all metabolic peptides

See all 21 metabolic peptides ↓

How metabolic peptides work

GLP-1 agonists boost insulin release when blood sugar is high, lower glucagon, slow stomach emptying and reduce appetite.[1][12] The first, exenatide, came from a peptide found in Gila monster venom.[7] Tirzepatide adds activity at the GIP receptor.[2]

Amylin analogs such as pramlintide copy a hormone released with insulin. Taken with mealtime insulin, pramlintide slows stomach emptying and blunts the rise in blood sugar after meals.[8][28]

Glucagon combinations, including retatrutide, survodutide, mazdutide and pemvidutide, add glucagon receptor activity, which acts strongly on the liver. That is why several are being tested for fatty liver disease.[13][14]

Mitochondrial compounds aim at the cell’s energy machinery. MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA that acted on metabolism in mice.[16] NAD+ is a coenzyme cells need to turn food into energy.[19] SLU-PP-332 switches on exercise-related genes in mice.[21]

Peptides for blood sugar and type 2 diabetes

This is where the evidence is strongest.

  • Tirzepatide: lowered HbA1c by 1.87 to 2.07 percentage points over 40 weeks in SURPASS-1, versus a slight rise on placebo.[3]
  • Heart outcomes: liraglutide cut heart attack, stroke or cardiovascular death to 13.0% versus 14.9% on placebo in LEADER, and dulaglutide to 12.0% versus 13.4% in REWIND.[5][4] Once-weekly exenatide was shown to be safe for the heart in EXSCEL but did not significantly lower risk.[6]
  • Pramlintide: added modest benefit to insulin in type 1 diabetes, lowering HbA1c by 0.29 to 0.34 points over a year versus 0.04 on placebo.[8] Brand-name Symlin, Byetta and Bydureon BCise are now discontinued in the US; see our pramlintide and exenatide profiles.
  • Pipeline drugs: retatrutide lowered HbA1c by 1.69 to 1.94 points versus 0.81 on placebo in TRANSCEND-T2D-1.[9] Mazdutide lowered weight more than dulaglutide in Chinese adults with type 2 diabetes.[10] Orforglipron lowered HbA1c more than oral semaglutide in ACHIEVE-3, though it is approved in the US only for weight management so far.[11]

Several approvals now reach beyond blood sugar. Ozempic is also approved to lower the risk of heart attack, stroke and cardiovascular death in adults with type 2 diabetes and heart disease, and to lower kidney and cardiovascular risk in adults with type 2 diabetes and chronic kidney disease.[1] Mounjaro is approved to lower cardiovascular risk in adults with type 2 diabetes at high risk.[2] These outcome results, rather than HbA1c alone, are what set the approved drugs apart from compounds promoted online for “metabolic health.”

Fatty liver, belly fat and mitochondria

Fatty liver (MASH): Wegovy received accelerated approval in 2025 for MASH with moderate to advanced liver fibrosis.[12] In a phase 2 trial, up to 62% of people on survodutide had MASH improvement without worse fibrosis, versus 14% on placebo.[13] Pemvidutide resolved MASH more often than placebo, but fibrosis did not improve significantly more.[14]

Visceral fat: tesamorelin is approved to reduce deep belly fat in adults with HIV-associated lipodystrophy. In its first phase 3 trial, visceral fat fell 15.2% versus a 5.0% rise on placebo.[15] It is not approved for general weight loss; see growth hormone peptides.

Mitochondrial and energy compounds: these are heavily marketed but thinly studied in people.

  • MOTS-c protected mice from diet-induced obesity and insulin resistance.[16] FDA says it has found no human exposure data by any route.[17]
  • NAD+ given by IV in a small pilot study did not change blood levels for two hours, then rose by about 400% by six hours.[19] In a trial of the precursor NMN in women with prediabetes, muscle insulin sensitivity improved, but blood sugar, blood pressure and body composition did not.[20]
  • SLU-PP-332 and 5-Amino-1MQ raised energy use or reduced fat in mice; neither has been tested in people.[21][22]

Metabolic vs weight loss peptides

The two categories overlap because most GLP-1 drugs lower both weight and blood sugar. The difference is the goal and how success is measured. Weight loss peptides are judged by percentage of body weight lost. Metabolic peptides are judged by HbA1c, liver fat, cholesterol and heart outcomes. Dulaglutide, for example, lowered heart risk in REWIND[4] and is approved for type 2 diabetes but not for weight loss (see our dulaglutide profile). Compounds promoted for “energy” or healthy aging, such as NAD+, overlap with longevity peptides.

Safety, legality and sports rules

Approved drugs: stomach side effects are the most common. Semaglutide and tirzepatide carry a boxed warning about thyroid C-cell tumors seen in rodents, and low blood sugar becomes more likely when they are combined with insulin or sulfonylureas.[1][2]

Compounded and online products: FDA warns against unapproved semaglutide, tirzepatide, retatrutide, survodutide and mazdutide sold “for research purposes,” whose quality is unknown.[25] The American Diabetes Association recommends against compounded GLP-1 products.[26] FDA lists MOTS-c among substances nominated for compounding and then withdrawn, noting it has no human exposure data.[23] In July 2026 an FDA advisory committee reportedly voted 7 to 5 to recommend MOTS-c for compounding; the vote is not binding.[18] FDA’s 503A nominations list includes NAD among substances still under evaluation.[24]

For compounds that act on energy and muscle in exercise, see performance peptides.