Network meta-analysis of 83 RCTs finds sildenafil 100mg has the highest odds ratio (9.06) vs placebo — funded by sildenafil's manufacturer
Journal: The Journal of Sexual Medicine | Published: 2026-06-05 | Type: Systematic Review, Network Meta-Analysis | PMID: 42296271 Authors: Salonia A (Vita-Salute San Raffaele University, Milan), Burnett A (Johns Hopkins), Mulhall JP (Memorial Sloan Kettering), Hassan T (Viatris Inc., NY), Vignesh SO (Viatris, Bengaluru), and others Funding/COI: Funded by Viatris Inc. and the Italian Ministry of University. Two co-authors (Hassan, Vignesh) are Viatris employees. COI not formally declared in available data.
This network meta-analysis pooled 83 double-blind, placebo-controlled RCTs to rank four FDA/EMA-approved PDE5 inhibitors by dose-specific efficacy, using rate of achieving an IIEF erectile function domain score >26 as the primary outcome. Sildenafil ranked highest at both approved on-demand doses, followed by vardenafil 10mg, tadalafil 20mg, and avanafil. The problem is impossible to ignore: Viatris — a major manufacturer of generic sildenafil — funded the study and placed two of its medical affairs employees in the author list. The conclusion that sildenafil is the superior drug is not independently produced.
The methodological skeleton here is solid: restricting inclusion to double-blind, placebo-controlled RCTs minimizes performance and detection bias, and a network meta-analysis is the appropriate design when direct head-to-head comparisons between all agents and doses don't exist at scale. The threshold analysis — testing how much the data would have to shift to change the rankings — adds a useful robustness check rarely seen in NMAs of this type. Dose-specific analysis genuinely fills a gap; prior meta-analyses typically collapsed all doses of a drug together.
That said, 83 studies yielding 6,029 participants means an average of ~73 participants per trial — most of the underlying studies are small. The primary endpoint (IIEF EF >26) is one reasonable threshold but not the only one; results could look different under other definitions of "response." The avanafil arm has notably fewer trials and participants than sildenafil or tadalafil, which likely explains its wide CIs. Indirect comparisons through a network are also inherently weaker than direct head-to-head RCTs, and the authors' own caveat about "wide CI" and "potential uncertainty" appears to be underplayed in the conclusion.
On its technical merits, this is a well-constructed NMA: the inclusion criteria are tight, the threshold analysis is a genuine plus, and dose-specific comparisons fill a real gap in the literature. The finding that sildenafil 100mg and 50mg have the highest odds ratios versus placebo may even be correct. But "may be correct" is the operative phrase — because Viatris paid for this, employs two of the authors, and manufactures the drug that wins. That funding structure doesn't automatically invalidate the math, but it means the NMA rankings should be treated as a hypothesis worth independent replication, not a settled comparative verdict. Read the methodology; don't swallow the conclusion.