Comparison of 3 Dual Single-Pill Combinations for Blood Pressure Lowering: A Secondary Analysis of an International Randomized Trial
Aletta E. SchutteAbdul SalamWilliam C. CushmanAsita de SilvaGian Luca Di TannaDiederick E. GrobbeeKrzysztof NarkiewiczDike OjjiNeil R PoulterMarkus P. SchlaichWilko SpieringBryan WilliamsJackson T. WrightT. KumananPeter HayGamini GalappatthyTanya PereiraFaslur RahumanArjuna P. De SilvaGodwin ConstantineChristopher GianacasStephen Vander HoornMathangi ShanthakumarXiaoqiu LiuNelson WangSonali R. GnanenthiranPaul K. WheltonAnthony Rodgersfor the GMRx2 Investigators
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Why the study?
Does dual single-pill combination therapy with telmisartan-indapamide reduce home systolic blood pressure more effectively than telmisartan-amlodipine or amlodipine-indapamide in adults with hypertension?
Key Points
- To compare the blood pressure-lowering efficacy and safety of three dual single-pill combinations containing telmisartan, amlodipine, or indapamide.
- Secondary analysis of an international, double-blind randomized trial conducted across 7 countries (NCT04518293).
- Following a 4-week single-blind run-in with low-dose triple therapy, N=834 participants with systolic blood pressure 110 to 154 mm Hg were randomized to telmisartan-indapamide (TI), telmisartan-amlodipine (TA), or amlodipine-indapamide (AI) for 12 weeks with dose doubling at 6 weeks.
- The primary outcome was change in mean home systolic blood pressure from randomization to week 12, evaluated using hierarchical linear modeling.
- Least-squares mean difference in home systolic blood pressure change to week 12 was −3.1 mm Hg (95% CI, −4.4 to −1.8; P <0.001) for TI versus TA and −2.1 mm Hg (95% CI, −3.4 to −0.7; P =0.003) for TI versus AI.
- Mean home systolic blood pressure at week 12 was 127 mm Hg (95% CI, 126–128) for TI, 130 mm Hg (95% CI, 129–131) for TA, and 129 mm Hg (95% CI, 128–130) for AI, with home blood pressure control (<130/80 mm Hg) achieved in 44%, 39%, and 33%, respectively.
- Discontinuation due to adverse events was 1.4% with TI, 1.1% with TA, and 1.4% with AI, while hypokalemia (<3.5 mmol/L) occurred in 4.7%, 0%, and 12.7% of participants, respectively.
Study Design
Type
RCT (n=834)
Blinding
Double-blind
Randomization
Randomized
Multicenter
Yes
Structured PICO
Does dual single-pill combination therapy with telmisartan-indapamide reduce home systolic blood pressure more effectively than telmisartan-amlodipine or amlodipine-indapamide in adults with hypertension?
P
Population
834 adults with hypertension (mean age 59 years, 52% female) and a baseline systolic blood pressure of 110 to 154 mm Hg after a run-in period, followed for 12 weeks.
I
Intervention
Dual single-pill combination of telmisartan-indapamide (TI) (telmisartan 20 mg and indapamide 1.25 mg, doubled after 6 weeks unless contraindicated) administered for 12 weeks.
C
Comparator
Alternative dual single-pill combinations: telmisartan-amlodipine (TA) (20 mg/2.5 mg) or amlodipine-indapamide (AI) (2.5 mg/1.25 mg), with doses similarly doubled after 6 weeks.
O
Outcome
Change in mean home systolic blood pressure (BP) from randomization to week 12.surrogate
Main Result
Mean Difference: -3.1 (95% CI -4.4–-1.8)
Absolute Event Rate: 127% vs 130%
p-value: p=<0.001
Telmisartan-indapamide dual therapy provided a modest but statistically significant greater reduction in home systolic blood pressure compared to telmisartan-amlodipine or amlodipine-indapamide, though all combinations were effective and well tolerated.
Limitations
- Secondary analysis of a trial not specifically powered for comparisons between dual combinations
- Antihypertensive dose levels were limited
- Analyses were not prespecified with potential type I error inflation attributable to multiple comparisons
- Run-in phase may have selected participants more tolerant of combination therapy, limiting generalizability and underestimating adverse events
- Clinic BP comparisons were less precise than home BP measurements
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“GMRx2 reduced BP quickly in mild-to-moderate hypertension and more effectively than dual therapy in a broad, large hypertensive population, without safety concerns. The availability of an SPC could help to reduce current therapeutic inertia, helping patients achieve BP control quickly in a small number of steps, with potential benefits for improved adherence.”
Implication
Telmisartan-indapamide may be considered first among these dual single-pill combinations; extends randomized comparative data on dual antihypertensive regimens.
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Cite This Study
Schutte et al. (2026) conducted an RCT in Hypertension (n=834). Telmisartan-indapamide (TI) vs. Telmisartan-amlodipine (TA) and amlodipine-indapamide (AI) was evaluated on Change in mean home systolic blood pressure from randomization to week 12 (MD -3.1 mm Hg, 95% CI -4.4 to -1.8, p=<0.001).