Nebivolol
Nebivolol lowers blood pressure through beta1 blockade and nitric-oxide-linked vasodilation. Compared with some older beta blockers, it can better preserve erectile function and metabolic measures. That is a useful clinical distinction; evidence for boosting healthy libido, testosterone or athletic performance is much weaker.
Racemic beta1-selective blocker with vasodilatory properties
- FDA approval covers hypertension. The US label has no heart-failure or enhancement indication.
- SENIORS improved a composite of death or cardiovascular hospitalization; mortality alone was not significant.
- Controlled comparisons found better erectile and metabolic tolerability than some older beta blockers; CYP2D6 changes exposure.
- Abrupt withdrawal and combinations with other rate-slowing drugs can be dangerous.
Is nebivolol an approved blood-pressure drug or an experimental nitric-oxide compound?
US approval covers hypertension, and the label says controlled nebivolol trials have not shown cardiovascular-risk reduction. The UK SmPC also covers stable mild or moderate heart failure in patients 70 or older, based on evidence that includes SENIORS.
US label · hypertension, CYP2D6 PK, and safety
FDA prescribing information
AvKARE, LLC. NEBIVOLOL tablets. DailyMed setid 1ce89dc5-018d-db40-e063-6294a90a9722. Updated January 16, 2026.
The current US label covers hypertension, states that controlled nebivolol trials have not demonstrated cardiovascular-risk reduction, describes beta1 blockade plus vasodilatory activity, and documents large CYP2D6 phenotype differences in exposure and half-life.
- Participants / model
- Adults with hypertension; pharmacokinetic studies included CYP2D6 extensive and poor metabolizers
- Treatment
- Oral racemic nebivolol hydrochloride tablets
- Follow-up
- Current product record; pharmacokinetic observations after single and repeated oral exposure
- Study design
- Regulatory prescribing information
This label establishes the U.S. indication. It does not create a U.S. heart-failure indication from trials or foreign product information.
Read the original sourceUK SmPC · hypertension and elderly heart failure
UK official product information
Ipca Laboratories UK Ltd. Nebivolol 5mg Tablets, Summary of Product Characteristics. Text revised June 10, 2025.
The UK SmPC lists essential hypertension and adjunctive treatment of stable mild or moderate chronic heart failure in patients aged 70 years or older.
- Participants / model
- Adults with essential hypertension; patients aged 70 or older with stable mild or moderate chronic heart failure
- Treatment
- Oral nebivolol tablets
- Follow-up
- Current product record
- Study design
- Regulatory product information
UK indications and contraindications cannot be assumed to be US indications.
Read the original sourcePubChem CID 71301 · nebivolol identity
Government substance database
National Library of Medicine. PubChem Compound Summary for CID 71301, Nebivolol.
Identifies nebivolol base as C22H25F2NO4, molecular weight 405.4 g/mol, CID 71301.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Living database record
- Study design
- Curated chemical identity record
The US tablet label supplies the racemic hydrochloride salt; the base and salt have different molecular weights.
Read the original sourceWhat exactly improved in the large heart-failure trial?
SENIORS enrolled 2,135 adults aged 70 or older with heart failure and analyzed 2,128. Over a mean 21 months, death or cardiovascular hospitalization occurred in 31.1% with nebivolol and 35.3% with placebo, an absolute difference of 4.2 percentage points (HR 0.86, 95% CI 0.74 to 0.99). Mortality alone was 15.8% versus 18.1% and was not significant.
| Outcome | Nebivolol | Placebo | Estimate |
|---|---|---|---|
| Death or cardiovascular hospitalization | 31.1% | 35.3% | HR 0.86, 95% CI 0.74 to 0.99; p=0.039 |
| All-cause death | 15.8% | 18.1% | HR 0.88; p=0.21 |
| Any adverse event | 85.4% | 84.8% | Bradycardia 11.1% vs 2.6%; adverse-event discontinuation 15.5% vs 12.8% |
SENIORS · 2,128 older heart-failure patients
Randomized double-blind placebo-controlled trial
Marcus D. Flather, Marcelo C. Shibata, Andrew J. S. Coats, et al.; SENIORS Investigators. European Heart Journal. 2005. PMID 15642700.
Of 2,135 enrolled, 2,128 were analyzed. Death or cardiovascular hospitalization occurred in 31.1% with nebivolol and 35.3% with placebo (HR 0.86, 95% CI 0.74 to 0.99; p=0.039), an absolute difference of 4.2 percentage points. All-cause death was 15.8% versus 18.1% (HR 0.88; p=0.21).
- Participants / model
- 2,135 adults aged 70 or older with established heart failure enrolled; 2,128 analyzed
- Treatment
- Oral nebivolol, titrated in the trial, versus placebo
- Follow-up
- Mean follow-up 21 months
- Study design
- Randomized double-blind placebo-controlled multicenter trial
The benefit was driven by a composite; mortality alone was not significant. Adverse events were common in both groups, with more bradycardia and treatment discontinuation under nebivolol.
Read the original sourceUK SmPC · hypertension and elderly heart failure
UK official product information
Ipca Laboratories UK Ltd. Nebivolol 5mg Tablets, Summary of Product Characteristics. Text revised June 10, 2025.
The UK SmPC lists essential hypertension and adjunctive treatment of stable mild or moderate chronic heart failure in patients aged 70 years or older.
- Participants / model
- Adults with essential hypertension; patients aged 70 or older with stable mild or moderate chronic heart failure
- Treatment
- Oral nebivolol tablets
- Follow-up
- Current product record
- Study design
- Regulatory product information
UK indications and contraindications cannot be assumed to be US indications.
Read the original sourceDoes nebivolol have a proven endothelial advantage over other beta-blockers?
In 12 adults with essential hypertension, both nebivolol/diuretic and atenolol/diuretic lowered clinic pressure from about 154/97 to 132/82 to 83 mm Hg over eight weeks. Acetylcholine-stimulated forearm blood flow improved only during nebivolol and the response was blunted by nitric-oxide-synthase inhibition; nitroprusside responses were unchanged. This invasive physiology crossover had no clinical-event endpoint.
12 hypertensive patients · endothelial surrogate
Randomized double-blind crossover trial
N. Tzemos, P. O. Lim, and T. M. MacDonald. Circulation. 2001. PMID 11479245.
Both combinations lowered clinic pressure from about 154/97 to 132/82 to 83 mm Hg. Maximum acetylcholine-stimulated forearm blood flow improved to 435±27% during nebivolol, and L-NMMA reduced that response by 54±5%; nitroprusside responses did not differ.
- Participants / model
- 12 adults with essential hypertension
- Treatment
- Nebivolol plus bendrofluazide versus atenolol plus bendrofluazide
- Follow-up
- Two 8-week treatment periods after a 2-week placebo run-in
- Study design
- Randomized double-blind crossover physiologic study
Twelve-person, eight-week crossover measuring invasive vascular physiology. The comparison included the same diuretic in both arms and had no myocardial-infarction, hospitalization, or mortality endpoint.
Read the original sourceWhy does CYP2D6 status matter so much?
Nebivolol metabolism is highly phenotype sensitive. The US label reports about fivefold higher peak active d-nebivolol and tenfold higher exposure in poor metabolizers, with an active-enantiomer half-life around 19 hours instead of 12. Strong CYP2D6 inhibitors can push exposure in the same direction.
US label · hypertension, CYP2D6 PK, and safety
FDA prescribing information
AvKARE, LLC. NEBIVOLOL tablets. DailyMed setid 1ce89dc5-018d-db40-e063-6294a90a9722. Updated January 16, 2026.
The current US label covers hypertension, states that controlled nebivolol trials have not demonstrated cardiovascular-risk reduction, describes beta1 blockade plus vasodilatory activity, and documents large CYP2D6 phenotype differences in exposure and half-life.
- Participants / model
- Adults with hypertension; pharmacokinetic studies included CYP2D6 extensive and poor metabolizers
- Treatment
- Oral racemic nebivolol hydrochloride tablets
- Follow-up
- Current product record; pharmacokinetic observations after single and repeated oral exposure
- Study design
- Regulatory prescribing information
This label establishes the U.S. indication. It does not create a U.S. heart-failure indication from trials or foreign product information.
Read the original sourceDoes the Russian postmenopausal study change the clinical case?
The cited study reports 30 days of blood-pressure and cardiac-geometry subgroup outcomes. Its abstract says 62 women were examined, while the treatment arms total 45. That denominator mismatch and the small, short study keep the result secondary to larger trials.
Russian study · 45 treated postmenopausal women
Russian clinical comparative study
V. R. Veber, M. P. Rubanova, M. A. Ivanova, and S. V. Zhmaylova. Кардиоваскулярная терапия и профилактика. 2004;3(6), part II:15 to 19.
The Russian paper reports short-term blood-pressure changes across left-ventricular geometry subgroups after nebivolol or amlodipine. Its abstract says 62 women were examined, whereas the treatment groups in the methods total 45 (24 nebivolol, 21 amlodipine).
- Participants / model
- Postmenopausal women with arterial hypertension; abstract n=62 examined, methods n=45 allocated to treatment
- Treatment
- Nebivolol or amlodipine
- Follow-up
- 30 days
- Study design
- Comparative allocation described as double-blind; reporting of randomization and denominators is incomplete
The report contains an inconsistent denominator, very short follow-up, subgrouping, and surrogate outcomes that sharply limit inference.
Read the original sourceDo Russian hypertensive-rat findings prove a special human remodeling benefit?
In rats, chronic nebivolol affected blood pressure, endothelial relaxation, cardiac mass, and vascular remodeling more broadly than metoprolol, supporting the proposed nitric-oxide biology. Clinical-event questions still require human trials such as SENIORS.
Russian study · hypertensive rat remodeling
Russian preclinical animal study
V. I. Buvaltsev, S. Yu. Mashina, D. A. Pokidyshev, B. V. Smirin, L. A. Baida, I. Yu. Malyshev, E. B. Manukhina. Российский кардиологический журнал. 2002;(5/37):74 to 81.
In male stroke-prone spontaneously hypertensive and Wistar-Kyoto rats, chronic nebivolol and metoprolol were compared for blood pressure, cardiac mass, nitric-oxide biology, endothelial relaxation, and vascular remodeling; nebivolol showed broader nitric-oxide and remodeling effects in this model.
- Participants / model
- Male SHRSP and Wistar-Kyoto rats, at least 9 per experimental group
- Treatment
- Nebivolol or metoprolol versus untreated controls
- Follow-up
- 5 or 10 weeks
- Study design
- Controlled preclinical hypertension experiment
A rat nitric-oxide and remodeling experiment cannot establish human event reduction or a unique clinical advantage.
Read the original sourceSENIORS · 2,128 older heart-failure patients
Randomized double-blind placebo-controlled trial
Marcus D. Flather, Marcelo C. Shibata, Andrew J. S. Coats, et al.; SENIORS Investigators. European Heart Journal. 2005. PMID 15642700.
Of 2,135 enrolled, 2,128 were analyzed. Death or cardiovascular hospitalization occurred in 31.1% with nebivolol and 35.3% with placebo (HR 0.86, 95% CI 0.74 to 0.99; p=0.039), an absolute difference of 4.2 percentage points. All-cause death was 15.8% versus 18.1% (HR 0.88; p=0.21).
- Participants / model
- 2,135 adults aged 70 or older with established heart failure enrolled; 2,128 analyzed
- Treatment
- Oral nebivolol, titrated in the trial, versus placebo
- Follow-up
- Mean follow-up 21 months
- Study design
- Randomized double-blind placebo-controlled multicenter trial
The benefit was driven by a composite; mortality alone was not significant. Adverse events were common in both groups, with more bradycardia and treatment discontinuation under nebivolol.
Read the original sourceWhich hazards and interactions are easy to miss?
Abrupt beta-blocker withdrawal can precipitate ischemia or infarction. Excess exposure can cause bradycardia, hypotension, heart block, bronchospasm, or worsening heart failure. Verapamil, diltiazem, digitalis glycosides, other beta-blockers, and CYP2D6 inhibitors need clinical review; beta blockade can also mask hypoglycemia and warning signs of hyperthyroidism.
US label · hypertension, CYP2D6 PK, and safety
FDA prescribing information
AvKARE, LLC. NEBIVOLOL tablets. DailyMed setid 1ce89dc5-018d-db40-e063-6294a90a9722. Updated January 16, 2026.
The current US label covers hypertension, states that controlled nebivolol trials have not demonstrated cardiovascular-risk reduction, describes beta1 blockade plus vasodilatory activity, and documents large CYP2D6 phenotype differences in exposure and half-life.
- Participants / model
- Adults with hypertension; pharmacokinetic studies included CYP2D6 extensive and poor metabolizers
- Treatment
- Oral racemic nebivolol hydrochloride tablets
- Follow-up
- Current product record; pharmacokinetic observations after single and repeated oral exposure
- Study design
- Regulatory prescribing information
This label establishes the U.S. indication. It does not create a U.S. heart-failure indication from trials or foreign product information.
Read the original sourceUK SmPC · hypertension and elderly heart failure
UK official product information
Ipca Laboratories UK Ltd. Nebivolol 5mg Tablets, Summary of Product Characteristics. Text revised June 10, 2025.
The UK SmPC lists essential hypertension and adjunctive treatment of stable mild or moderate chronic heart failure in patients aged 70 years or older.
- Participants / model
- Adults with essential hypertension; patients aged 70 or older with stable mild or moderate chronic heart failure
- Treatment
- Oral nebivolol tablets
- Follow-up
- Current product record
- Study design
- Regulatory product information
UK indications and contraindications cannot be assumed to be US indications.
Read the original sourceIs it better for erections than other beta blockers?
Several controlled comparisons favor nebivolol over metoprolol or atenolol. Most show preservation of sexual function when blood-pressure treatment is needed, rather than an increase above baseline.
In a blinded 131-person trial, successful intercourse episodes per month stayed roughly stable with nebivolol (6.4 to 6.0), while they fell with atenolol (7.0 to 3.7) and atenolol plus chlorthalidone (6.4 to 2.8). Participants had hypertension and no ED at entry.
MR NOED and later crossover comparisons also generally favored nebivolol. Results varied by baseline ED, and a coronary-bypass study reported within-group changes that cannot by themselves establish a between-group protective effect.
An uncontrolled switch study found improvement in 20 of 29 men who had ED on another beta blocker. Stopping the previous drug, expectation and regression to the mean could contribute. Isolated human erectile tissue and diabetic-rat experiments support an NO/cGMP mechanism, but are not oral-human treatment trials.
MR NOED: randomized blinded crossover
Randomized controlled human trial
Brixius K, Middeke M, Lichtenthal A, Jahn E, Schwinger RH. Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men. Clinical and experimental pharmacology & physiology. 2007. DOI 10.1111/j.1440-1681.2007.04551.x.
Hypertensive men without prior sexual dysfunction received 12-week periods of nebivolol and metoprolol with a placebo washout. BP lowering was similar. Metoprolol reduced the IIEF erectile subscore by 0.92 during the initial eight weeks; nebivolol did not, and some secondary sexual scores favored it. This is comparative tolerability in a selected population, not a large placebo-controlled ED-treatment effect.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
The abstract does not report the allocation method.
Read the original sourceBoydak et al., 131-person randomized sexual-function comparison
Primary human study
Boydak B, Nalbantgil S, Fici F, Nalbantgil I, Zoghi M, Ozerkan F, Tengiz I, Ercan E, Yilmaz H, Yoket U, Onder R. A Randomised Comparison of the Effects of Nebivolol and Atenolol with and without Chlorthalidone on the Sexual Function of Hypertensive Men. Clinical drug investigation. 2005. DOI 10.2165/00044011-200525060-00006.
Previously untreated hypertensive men without ED were randomized double-blind to nebivolol, atenolol, or atenolol plus chlorthalidone for 12 weeks. Successful intercourse episodes per month remained approximately stable with nebivolol (6.4 to 6.0) and fell with atenolol (7.0 to 3.7) and its diuretic combination (6.4 to 2.8). BP and heart rate fell in all arms. Questionnaire outcomes and selected heterosexual partnered men limit generalization; the data support preservation, not increased baseline libido.
Read the original sourceDoumas et al., switching beta blockers to nebivolol
Primary human study
Doumas M, Tsakiris A, Douma S, Grigorakis A, Papadopoulos A, Hounta A, Tsiodras S, Dimitriou D, Giamarellou H. Beneficial effects of switching from beta-blockers to nebivolol on the erectile function of hypertensive patients. Asian journal of andrology. 2006. DOI 10.1111/j.1745-7262.2006.00076.x.
Forty-four men were switched from another beta blocker; 29 had ED. At three months, 20 of those 29 improved and 11 normalized by the study measure. There was no randomized concurrent control. Withdrawal of the prior drug, expectation and regression to the mean cannot be separated from nebivolol's effect.
Read the original sourceAldemir et al., 60-person CABG randomized comparison
Randomized controlled human trial
Aldemir M, Keleş İ, Karalar M, Tecer E, Adalı F, Pektaş MB, Parlar Aİ, Darçın OT. Nebivolol compared with metoprolol for erectile function in males undergoing coronary artery bypass graft. Anatolian journal of cardiology. 2016. DOI 10.5152/akd.2015.5936.
Nebivolol or metoprolol was given around coronary bypass surgery. IIEF-5 declined from 15.2 to 12.9 with metoprolol and from 12.9 to 12.4 with nebivolol. These reported within-group tests are not sufficient by themselves to quantify a between-group protective effect; baseline scores differed and surgery is a strong cointervention. The finding adds context, not healthy-person enhancement proof.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Gungor et al., 2022 crossover across ED subtypes
Randomized controlled human trial
Gungor G, Perk H, Soyupek S, Baykal B, Demir M, Sezer MT. Nebivolol protects erectile functions compared to Metoprolol in hypertensive men with atherogenic, venogenic, psychogenic erectile dysfunction: A prospective, randomized, cross-over, clinical trial. European journal of internal medicine. 2022. DOI 10.1016/j.ejim.2022.06.013.
One-month treatment periods with a drug-free crossover interval compared nebivolol and metoprolol in hypertensive men. Nebivolol generally preserved IIEF-5 in ED subgroups while metoprolol worsened it. In men without ED, both lowered the score, although metoprolol did more. The abstract does not report the sample count or all between-arm estimates, so those are not invented. Increased NO and a modest correlation with IIEF do not prove the causal mechanism.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Human penile tissue and diabetic-rat NO/cGMP experiment
Primary preclinical study
Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, Sáenz de Tejada I. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling. The journal of sexual medicine. 2010. DOI 10.1111/j.1743-6109.2010.01710.x.
Nebivolol enhanced NO/cGMP responses in isolated human erectile tissues and improved erectile responses in diabetic rats. Human tissue in a bath is not a treated human cohort. The study supplies a plausible mechanism for comparative sexual tolerability, but not oral-human ED efficacy or a safe combination protocol with PDE5 inhibitors.
Read the original sourceDoes it improve insulin sensitivity or testosterone?
The better-supported metabolic result is neutrality versus deterioration on metoprolol. The testosterone claim rests on a small Russian study with reporting problems.
A randomized 46-person metabolic-syndrome study found similar blood-pressure and heart-rate reductions. Insulin sensitivity declined on metoprolol and changed little on nebivolol; the difference in change was significant (p=.03). Beta-cell function and the other insulin-response measures did not improve.
In a Russian 40-person nebivolol-versus-valsartan report, IIEF rose from 15.3 to 16.4 with nebivolol, and testosterone from 11.38 to 11.74 nmol/L. The abstract calls the study blinded, but the methods call it open. Small arms, multiple endpoints and unclear concealment make this exploratory evidence, not reliable testosterone restoration.
Ayers et al., nebivolol and metoprolol in metabolic syndrome
Randomized controlled human trial
Ayers K, Byrne LM, DeMatteo A, Brown NJ. Differential effects of nebivolol and metoprolol on insulin sensitivity and plasminogen activator inhibitor in the metabolic syndrome. Hypertension (Dallas, Tex. : 1979). 2012. DOI 10.1161/hypertensionaha.111.189589.
Forty-six participants underwent glucose-tolerance phenotyping before and after 12 weeks of randomized treatment. Both drugs lowered BP and heart rate similarly. Insulin sensitivity declined with metoprolol and changed little with nebivolol; the difference in change was significant (p=.03). Beta-cell function, disposition index and acute insulin response did not change. The correct conclusion is comparative metabolic neutrality, not direct insulin sensitization.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Nedogoda et al., Russian 40-person nebivolol-versus-valsartan report
Primary human study
Nedogoda et al., Russian 40-person nebivolol-versus-valsartan report. https://medi.ru/info/8918/
Men with hypertension, metabolic syndrome and ED were assigned by envelopes to 20-person arms for 12 weeks. The abstract calls the trial blinded, but the methods explicitly call it open. IIEF rose from 15.3 to 16.4 with nebivolol versus 14.55 to 14.6 with valsartan; total testosterone rose only from 11.38 to 11.74 nmol/L. The paper reports favorable subgroup/surrogate changes and no adverse events. Multiple testing, unclear concealment, the blinding contradiction, unusual hormone-sampling choices and inconsistent table labels reduce confidence. This is relevant regional evidence, not grounds to market nebivolol as testosterone therapy.
Read the original sourceStudies and sources
US label · hypertension, CYP2D6 PK, and safety
FDA prescribing information
AvKARE, LLC. NEBIVOLOL tablets. DailyMed setid 1ce89dc5-018d-db40-e063-6294a90a9722. Updated January 16, 2026.
The current US label covers hypertension, states that controlled nebivolol trials have not demonstrated cardiovascular-risk reduction, describes beta1 blockade plus vasodilatory activity, and documents large CYP2D6 phenotype differences in exposure and half-life.
- Participants / model
- Adults with hypertension; pharmacokinetic studies included CYP2D6 extensive and poor metabolizers
- Treatment
- Oral racemic nebivolol hydrochloride tablets
- Follow-up
- Current product record; pharmacokinetic observations after single and repeated oral exposure
- Study design
- Regulatory prescribing information
This label establishes the U.S. indication. It does not create a U.S. heart-failure indication from trials or foreign product information.
Read the original sourceUK SmPC · hypertension and elderly heart failure
UK official product information
Ipca Laboratories UK Ltd. Nebivolol 5mg Tablets, Summary of Product Characteristics. Text revised June 10, 2025.
The UK SmPC lists essential hypertension and adjunctive treatment of stable mild or moderate chronic heart failure in patients aged 70 years or older.
- Participants / model
- Adults with essential hypertension; patients aged 70 or older with stable mild or moderate chronic heart failure
- Treatment
- Oral nebivolol tablets
- Follow-up
- Current product record
- Study design
- Regulatory product information
UK indications and contraindications cannot be assumed to be US indications.
Read the original sourceSENIORS · 2,128 older heart-failure patients
Randomized double-blind placebo-controlled trial
Marcus D. Flather, Marcelo C. Shibata, Andrew J. S. Coats, et al.; SENIORS Investigators. European Heart Journal. 2005. PMID 15642700.
Of 2,135 enrolled, 2,128 were analyzed. Death or cardiovascular hospitalization occurred in 31.1% with nebivolol and 35.3% with placebo (HR 0.86, 95% CI 0.74 to 0.99; p=0.039), an absolute difference of 4.2 percentage points. All-cause death was 15.8% versus 18.1% (HR 0.88; p=0.21).
- Participants / model
- 2,135 adults aged 70 or older with established heart failure enrolled; 2,128 analyzed
- Treatment
- Oral nebivolol, titrated in the trial, versus placebo
- Follow-up
- Mean follow-up 21 months
- Study design
- Randomized double-blind placebo-controlled multicenter trial
The benefit was driven by a composite; mortality alone was not significant. Adverse events were common in both groups, with more bradycardia and treatment discontinuation under nebivolol.
Read the original source12 hypertensive patients · endothelial surrogate
Randomized double-blind crossover trial
N. Tzemos, P. O. Lim, and T. M. MacDonald. Circulation. 2001. PMID 11479245.
Both combinations lowered clinic pressure from about 154/97 to 132/82 to 83 mm Hg. Maximum acetylcholine-stimulated forearm blood flow improved to 435±27% during nebivolol, and L-NMMA reduced that response by 54±5%; nitroprusside responses did not differ.
- Participants / model
- 12 adults with essential hypertension
- Treatment
- Nebivolol plus bendrofluazide versus atenolol plus bendrofluazide
- Follow-up
- Two 8-week treatment periods after a 2-week placebo run-in
- Study design
- Randomized double-blind crossover physiologic study
Twelve-person, eight-week crossover measuring invasive vascular physiology. The comparison included the same diuretic in both arms and had no myocardial-infarction, hospitalization, or mortality endpoint.
Read the original sourceRussian study · 45 treated postmenopausal women
Russian clinical comparative study
V. R. Veber, M. P. Rubanova, M. A. Ivanova, and S. V. Zhmaylova. Кардиоваскулярная терапия и профилактика. 2004;3(6), part II:15 to 19.
The Russian paper reports short-term blood-pressure changes across left-ventricular geometry subgroups after nebivolol or amlodipine. Its abstract says 62 women were examined, whereas the treatment groups in the methods total 45 (24 nebivolol, 21 amlodipine).
- Participants / model
- Postmenopausal women with arterial hypertension; abstract n=62 examined, methods n=45 allocated to treatment
- Treatment
- Nebivolol or amlodipine
- Follow-up
- 30 days
- Study design
- Comparative allocation described as double-blind; reporting of randomization and denominators is incomplete
The report contains an inconsistent denominator, very short follow-up, subgrouping, and surrogate outcomes that sharply limit inference.
Read the original sourceRussian study · hypertensive rat remodeling
Russian preclinical animal study
V. I. Buvaltsev, S. Yu. Mashina, D. A. Pokidyshev, B. V. Smirin, L. A. Baida, I. Yu. Malyshev, E. B. Manukhina. Российский кардиологический журнал. 2002;(5/37):74 to 81.
In male stroke-prone spontaneously hypertensive and Wistar-Kyoto rats, chronic nebivolol and metoprolol were compared for blood pressure, cardiac mass, nitric-oxide biology, endothelial relaxation, and vascular remodeling; nebivolol showed broader nitric-oxide and remodeling effects in this model.
- Participants / model
- Male SHRSP and Wistar-Kyoto rats, at least 9 per experimental group
- Treatment
- Nebivolol or metoprolol versus untreated controls
- Follow-up
- 5 or 10 weeks
- Study design
- Controlled preclinical hypertension experiment
A rat nitric-oxide and remodeling experiment cannot establish human event reduction or a unique clinical advantage.
Read the original sourcePubChem CID 71301 · nebivolol identity
Government substance database
National Library of Medicine. PubChem Compound Summary for CID 71301, Nebivolol.
Identifies nebivolol base as C22H25F2NO4, molecular weight 405.4 g/mol, CID 71301.
- Participants / model
- Not applicable
- Treatment
- Not applicable
- Follow-up
- Living database record
- Study design
- Curated chemical identity record
The US tablet label supplies the racemic hydrochloride salt; the base and salt have different molecular weights.
Read the original sourceAyers et al., nebivolol and metoprolol in metabolic syndrome
Randomized controlled human trial
Ayers K, Byrne LM, DeMatteo A, Brown NJ. Differential effects of nebivolol and metoprolol on insulin sensitivity and plasminogen activator inhibitor in the metabolic syndrome. Hypertension (Dallas, Tex. : 1979). 2012. DOI 10.1161/hypertensionaha.111.189589.
Forty-six participants underwent glucose-tolerance phenotyping before and after 12 weeks of randomized treatment. Both drugs lowered BP and heart rate similarly. Insulin sensitivity declined with metoprolol and changed little with nebivolol; the difference in change was significant (p=.03). Beta-cell function, disposition index and acute insulin response did not change. The correct conclusion is comparative metabolic neutrality, not direct insulin sensitization.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
MR NOED: randomized blinded crossover
Randomized controlled human trial
Brixius K, Middeke M, Lichtenthal A, Jahn E, Schwinger RH. Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men. Clinical and experimental pharmacology & physiology. 2007. DOI 10.1111/j.1440-1681.2007.04551.x.
Hypertensive men without prior sexual dysfunction received 12-week periods of nebivolol and metoprolol with a placebo washout. BP lowering was similar. Metoprolol reduced the IIEF erectile subscore by 0.92 during the initial eight weeks; nebivolol did not, and some secondary sexual scores favored it. This is comparative tolerability in a selected population, not a large placebo-controlled ED-treatment effect.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
The abstract does not report the allocation method.
Read the original sourceBoydak et al., 131-person randomized sexual-function comparison
Primary human study
Boydak B, Nalbantgil S, Fici F, Nalbantgil I, Zoghi M, Ozerkan F, Tengiz I, Ercan E, Yilmaz H, Yoket U, Onder R. A Randomised Comparison of the Effects of Nebivolol and Atenolol with and without Chlorthalidone on the Sexual Function of Hypertensive Men. Clinical drug investigation. 2005. DOI 10.2165/00044011-200525060-00006.
Previously untreated hypertensive men without ED were randomized double-blind to nebivolol, atenolol, or atenolol plus chlorthalidone for 12 weeks. Successful intercourse episodes per month remained approximately stable with nebivolol (6.4 to 6.0) and fell with atenolol (7.0 to 3.7) and its diuretic combination (6.4 to 2.8). BP and heart rate fell in all arms. Questionnaire outcomes and selected heterosexual partnered men limit generalization; the data support preservation, not increased baseline libido.
Read the original sourceDoumas et al., switching beta blockers to nebivolol
Primary human study
Doumas M, Tsakiris A, Douma S, Grigorakis A, Papadopoulos A, Hounta A, Tsiodras S, Dimitriou D, Giamarellou H. Beneficial effects of switching from beta-blockers to nebivolol on the erectile function of hypertensive patients. Asian journal of andrology. 2006. DOI 10.1111/j.1745-7262.2006.00076.x.
Forty-four men were switched from another beta blocker; 29 had ED. At three months, 20 of those 29 improved and 11 normalized by the study measure. There was no randomized concurrent control. Withdrawal of the prior drug, expectation and regression to the mean cannot be separated from nebivolol's effect.
Read the original sourceAldemir et al., 60-person CABG randomized comparison
Randomized controlled human trial
Aldemir M, Keleş İ, Karalar M, Tecer E, Adalı F, Pektaş MB, Parlar Aİ, Darçın OT. Nebivolol compared with metoprolol for erectile function in males undergoing coronary artery bypass graft. Anatolian journal of cardiology. 2016. DOI 10.5152/akd.2015.5936.
Nebivolol or metoprolol was given around coronary bypass surgery. IIEF-5 declined from 15.2 to 12.9 with metoprolol and from 12.9 to 12.4 with nebivolol. These reported within-group tests are not sufficient by themselves to quantify a between-group protective effect; baseline scores differed and surgery is a strong cointervention. The finding adds context, not healthy-person enhancement proof.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Gungor et al., 2022 crossover across ED subtypes
Randomized controlled human trial
Gungor G, Perk H, Soyupek S, Baykal B, Demir M, Sezer MT. Nebivolol protects erectile functions compared to Metoprolol in hypertensive men with atherogenic, venogenic, psychogenic erectile dysfunction: A prospective, randomized, cross-over, clinical trial. European journal of internal medicine. 2022. DOI 10.1016/j.ejim.2022.06.013.
One-month treatment periods with a drug-free crossover interval compared nebivolol and metoprolol in hypertensive men. Nebivolol generally preserved IIEF-5 in ED subgroups while metoprolol worsened it. In men without ED, both lowered the score, although metoprolol did more. The abstract does not report the sample count or all between-arm estimates, so those are not invented. Increased NO and a modest correlation with IIEF do not prove the causal mechanism.
- Study design
- Randomized controlled trial; blinding and comparator details are stated in the source result.
Nedogoda et al., Russian 40-person nebivolol-versus-valsartan report
Primary human study
Nedogoda et al., Russian 40-person nebivolol-versus-valsartan report. https://medi.ru/info/8918/
Men with hypertension, metabolic syndrome and ED were assigned by envelopes to 20-person arms for 12 weeks. The abstract calls the trial blinded, but the methods explicitly call it open. IIEF rose from 15.3 to 16.4 with nebivolol versus 14.55 to 14.6 with valsartan; total testosterone rose only from 11.38 to 11.74 nmol/L. The paper reports favorable subgroup/surrogate changes and no adverse events. Multiple testing, unclear concealment, the blinding contradiction, unusual hormone-sampling choices and inconsistent table labels reduce confidence. This is relevant regional evidence, not grounds to market nebivolol as testosterone therapy.
Read the original sourceHuman penile tissue and diabetic-rat NO/cGMP experiment
Primary preclinical study
Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, Sáenz de Tejada I. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling. The journal of sexual medicine. 2010. DOI 10.1111/j.1743-6109.2010.01710.x.
Nebivolol enhanced NO/cGMP responses in isolated human erectile tissues and improved erectile responses in diabetic rats. Human tissue in a bath is not a treated human cohort. The study supplies a plausible mechanism for comparative sexual tolerability, but not oral-human ED efficacy or a safe combination protocol with PDE5 inhibitors.
Read the original sourceWhy is Nebivolol in A tier?
A for cardiovascular use. It often preserves erections and insulin sensitivity better than older beta blockers. That does not establish a libido or metabolic boost above a healthy baseline. SENIORS improved a combined endpoint; mortality alone was nonsignificant.