Vyleesi vs Addyi: differences, evidence and safety

Vyleesi (bremelanotide) is an on-demand peptide injection that raised sexual desire scores and cut related distress in two phase 3 trials of 1,267 premenopausal women (Kingsberg 2019). Addyi (flibanserin) is a nightly pill that added about half a satisfying sexual event a month in a meta-analysis of 5,914 women (Jaspers 2016). Both are FDA-approved for low sexual desire with distress (HSDD). Since December 2025 Addyi also covers postmenopausal women under 65; Vyleesi does not. They have never been compared head to head.

Item	Vyleesi (bremelanotide)	Addyi (flibanserin)
US FDA status	Approved 2019-06-21 for premenopausal women with acquired, generalized HSDD (Drugs@FDA, NDA 210557)	Approved 2015-08-18 (Drugs@FDA, NDA 022526); since 12/2025 for women under 65, pre- or postmenopausal (Addyi label)
Compounding	Not on FDA’s Category 2 list (checked 2026-10-27); “PT-141” sold online was called an unapproved new drug in an FDA warning letter (FDA, 2026-08-24)	Not on FDA’s Category 2 list (FDA, checked 2026-10-27)
WADA	Not named on the 2026 List; S0 covers only substances with no government approval (WADA 2026). Not named in the 2027 List advisory (USADA)	Not named on the 2026 List or in USADA’s 2027 advisory
Strongest evidence	Approved label; 2 phase 3 RCTs	Approved label; 4 label RCTs and meta-analyses
Human trials	10 registered, 3 of them phase 3 (ClinicalTrials.gov, 2026-10-27)	20 registered, 12 of them phase 3 (ClinicalTrials.gov, 2026-10-27)
Next regulatory step	None announced	None announced
Last checked	2026-10-27	2026-10-27

Vyleesi vs Addyi at a glance

Feature	Vyleesi	Addyi
What it is	Cyclic heptapeptide (also called PT-141; Diamond 2006)	Benzimidazolone small molecule
Class	Melanocortin receptor agonist	Serotonin 5-HT1A agonist, 5-HT2A antagonist
Main receptors	MC1R and MC4R	5-HT1A, 5-HT2A
Research focus	Acquired, generalized HSDD	Acquired, generalized HSDD
Human evidence	2 phase 3 RCTs, n=1,267 (Kingsberg 2019)	Meta-analysis, 8 studies, n=5,914 (Jaspers 2016)
Who it is approved for	Premenopausal women	Women under 65, pre- or postmenopausal
WADA	Not named	Not named
Route	Under-the-skin autoinjector, on demand	Oral tablet, every night at bedtime
Half-life	About 2.7 hours	About 11 hours
Main safety concerns	Nausea, flushing, blood pressure rise, skin darkening	Dizziness, sleepiness, fainting with alcohol
Controlled substance	No schedule in the label	No schedule in the label

What is Vyleesi?

Vyleesi is the brand name of bremelanotide, a synthetic cyclic peptide of seven amino acids that is self-injected under the skin with an autoinjector before expected sexual activity (Vyleesi label). The FDA approved it in 2019 for premenopausal women with acquired, generalized HSDD: low desire that causes marked distress and is not explained by another condition, a relationship problem or a medication. Its label states it is not indicated for postmenopausal women, for men, or to enhance sexual performance. In the phase 3 trials most women used it two to three times a month. Bremelanotide is compared with another libido peptide on our PT-141 vs kisspeptin comparison.

What is Addyi?

Addyi is the brand name of flibanserin, a pink oral tablet taken once a day at bedtime (Addyi label). The FDA first approved it in 2015 for premenopausal women with acquired, generalized HSDD, and a label change dated 12/2025 widened the indication to women under 65, which now includes naturally postmenopausal women. It is not a peptide and not a hormone. The label sets bedtime use because taking it while awake raises the risk of low blood pressure, fainting, injury and sedation. It is not indicated for men or to enhance sexual performance.

How they work differently

• Vyleesi: it activates several melanocortin receptors, and at the doses used, MC1R and MC4R matter most; MC4R is found on nerve cells across the brain [Approved label] (Vyleesi label).
• Addyi: it acts as an agonist at the serotonin 5-HT1A receptor and blocks 5-HT2A, with weaker blocking of 5-HT2B, 5-HT2C and dopamine D4 receptors [Lab, in vitro, per label] (Addyi label).
• Vyleesi: MC1R sits on the skin’s pigment cells, which explains its skin-darkening side effect. The label states that how it improves HSDD is unknown.
• Addyi: its label also states that how it works in HSDD is not known. It is built for steady daily use, with a half-life of about 11 hours, against about 2.7 hours for bremelanotide.

Evidence head-to-head: Vyleesi vs Addyi

No trial has compared bremelanotide with flibanserin directly (PubMed and ClinicalTrials.gov, searched 2026-10-27). The figures below come from separate trials with different scales and durations, so any comparison between the columns is cross-trial.

Outcome	Vyleesi best evidence	Addyi best evidence
Sexual desire (FSFI desire score)	Human RCT, n=1,267: +0.35 vs placebo, integrated (Kingsberg 2019)	Meta-analysis, n=5,914: +0.27 vs placebo (Jaspers 2016)
Distress about low desire	Human RCT: -0.33 vs placebo, integrated (Kingsberg 2019)	Human RCT, n=1,087: lower distress, P ≤ 0.0001 (Katz 2013)
Satisfying sexual events a month	Not among the efficacy results in its label (label)	Meta-analysis: +0.49 a month vs placebo (Jaspers 2016)
Postmenopausal women	Not indicated; no postmenopausal efficacy data in label	Human RCT, n=949: desire and events improved, P < 0.01 (Simon 2014)
Arousal	Meta-analysis: improved FSFI arousal subscale (Toledo 2026)	Same meta-analysis: improved desire and total FSFI; no arousal gain reported

Vyleesi’s most promising result is its consistency: both RECONNECT trials met both main goals, with desire up 0.30 and 0.42 points over placebo and distress down 0.37 and 0.29 (Kingsberg 2019), and a prespecified analysis found the benefit held across age, weight and testosterone subgroups with few exceptions (Simon 2022). An independent re-analysis of the FDA data was far less positive: the odds of quitting for side effects were about 12 times higher on bremelanotide, and fewer completed the trial and went on to the open-label phase than on placebo (Spielmans 2021).

Addyi’s most promising result is the 24-week BEGONIA trial, where satisfying sexual events rose by 2.5 a month against 1.5 on placebo, with desire and distress also improved (Katz 2013). The limits are plain in its own label: two of its three premenopausal trials missed their daily-diary desire endpoint, and the postmenopausal trial added 0.4 events a month over placebo (Addyi label). The JAMA Internal Medicine meta-analysis graded the overall evidence quality as very low (Jaspers 2016).

Is Vyleesi or Addyi better? Which fits which goal?

Neither has been shown to be better, because no trial has put them side by side (searched 2026-10-27). For postmenopausal women under 65, Addyi has more evidence: a 949-woman trial in naturally postmenopausal women (Simon 2014) and an FDA indication, while Vyleesi’s label excludes them (Vyleesi label). Other options studied after menopause are covered in our guide to peptides for women over 40 and menopause. For a count of satisfying sexual events, Addyi again has more evidence, because that was a main endpoint of its trials (Jaspers 2016).

For on-demand use, Vyleesi is the only one of the two studied that way, and it carries no alcohol warning; its label reports that alcohol did not change bremelanotide levels in a study of a nasal form, while Addyi’s boxed warning restricts drinking around each dose (Addyi label). For desire together with arousal, a 2026 meta-analysis reported improvement in both with bremelanotide, and in desire, with no arousal gain reported, for flibanserin (Toledo 2026). These are evidence statements, not a pick: which drug suits a given woman, if either, is a decision for her clinician. The wider field is laid out on our ranking of libido peptides by evidence.

Can Vyleesi and Addyi be taken together?

No controlled human study of bremelanotide combined with flibanserin was found on PubMed or ClinicalTrials.gov (searched 2026-10-27). The 10 bremelanotide and 20 flibanserin records on ClinicalTrials.gov list no shared trial (bremelanotide; flibanserin). Neither label addresses the other drug. Both labels do flag blood pressure effects in opposite directions: Vyleesi raises it briefly after each dose, while Addyi can lower it (Vyleesi label). How the two would interact is unstudied, and any combination is a decision for a prescribing clinician.

Safety and regulatory status

Addyi’s main risks are in a boxed warning: using it with alcohol close in time, with moderate or strong CYP3A4 inhibitors (examples in the label include ketoconazole, clarithromycin, ritonavir and grapefruit juice) or in liver impairment raises the risk of severe low blood pressure and fainting (Addyi label). The label tells women to wait at least two hours after one or two drinks before the bedtime dose, and to skip the dose after three or more. In the premenopausal trials, dizziness affected 11.4% on Addyi against 2.2% on placebo, and sleepiness 11.2% against 2.9%; the label advises against driving for at least 6 hours after a dose. In a 96-woman alcohol study, no one fainted, but dizziness reached 39.8% at the highest alcohol level, against 31.1% on flibanserin alone (Simon 2020).

Vyleesi’s main risks are tolerability and blood pressure. Nausea hit 40% of users against 1% on placebo, mostly after the first dose; 13% needed anti-nausea medicine and 8% left the trials because of it (Vyleesi label). Flushing affected 20.3% and headache 11.3%. Blood pressure rose by up to 6/3 mmHg after each dose, usually back to baseline within 12 hours, so it is contraindicated with uncontrolled hypertension or known heart disease. Dark patches on the face, gums or breasts appeared in 1% at the labeled frequency and in 38% with eight daily doses, more often in women with dark skin, and did not always fade. It can lower levels of oral naltrexone. Across 43 studies in 3,500 people there were no deaths (Clayton 2022).

Where	Vyleesi	Addyi
US FDA	Approved 2019, premenopausal only (label)	Approved 2015; under 65 since 12/2025 (label)
Online “PT-141”	Called an unapproved new drug by FDA (2026 letter)	Not applicable
Sport (WADA)	Not named (WADA 2026)	Not named
Pregnancy	Animal data suggest possible fetal harm; contraception advised	No human pregnancy studies (label)

For athletes, the non-approved class S0 covers substances “not approved by any government regulatory authority” (USADA), which an FDA-approved Vyleesi or Addyi is not; a research-chemical “PT-141” product is a different matter, and athletes can check any product with their anti-doping agency. Anyone who suspects a side effect from Vyleesi, Addyi or any other drug or product can report it to the FDA through MedWatch.

How long do effects take in studies?

Both drugs were judged over 24 weeks in their main trials, and both labels say to stop after 8 weeks if there is no improvement (Addyi label; Vyleesi label). Vyleesi is used per occasion, but its label states that how long each dose works is unknown. Addyi is taken every night, and its effect was measured as a change over weeks rather than per dose. Its effect on weight was measured at week 24: in a post hoc analysis, 21.0% of premenopausal completers lost at least 5% of body weight by week 24, against 7.8% on placebo (Kornstein 2017).