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REFLECTIONS
Hypertension
Hypertension Global Newsletter #8 2025

Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, Hypertension
amlodipine and indapamide, compared with dual combinations for treatment of

hypertension: a randomised, double-blind, active-controlled, international clinical trial.
Rodgers A, et al. Lancet. 2024 Oct 18:404(10462):1536-1546

Recent hypertension guidelines recommend combinations of two blood pressure-lowering drugs as an initial treatment and earlier
use of triple-drug antihypertensive therapy, ideally as a single-pill combination (SPC). However, currently available triple-drug
SPCs are only indicated for individuals already taking all the three component drugs, or among those with inadequate blood
pressure control on two of the component drugs, and there are no existing SPC products with low doses of an angiotensin II
receptor blocker (ARB), a calcium channel blocker (CCB), and a thiazide-like diuretic. A new triple SPC of telmisartan, amlodipine,
and indapamide, named GMRx2, was developed to address this need. However, one of the key issues for any combination
product is the contribution of each component to the efficacy and tolerability.

This international, randomised trial was conducted among adults with hypertension to compare GMRx2 with each of the three dual
combinations for blood pressure-lowering efficacy and safety.

The primary efficacy outcome was a mean change
in home SBP from baseline to Week 12, and
the primary safety outcome was withdrawal of
treatment due to an adverse event from baseline
to Week 12. Secondary efficacy outcomes
included differences in clinic and home BP levels
and control rates.

Following a 4-week, single-blind, active run-in,
eligible participants were randomly allocated
to one of four 12-week treatments: GMRx2,
telmisartan-indapamide, telmisartan-amlodipine,
amlodipine-indapamide. A total of 1385 randomly
assigned participants were analysed (551 to
GMRx2 group, 276 to telmisartan-indapamide, 282
to telmisartan-amlodipine, and 276 to amlodipine-
indapamide). The average age across all four
groups was 59 years, with the percentage of male
participants at 48.6%. The mean baseline clinic
blood pressure for participants was 142/85 mmHg.

Looking at the primary efficacy outcome, home
SBP was lower in the GMRx2 group than in the
dual therapy groups. The least-squares differences
in change in home-seated mean SBP mmHg from
randomisation to Week 12 was –2.5 (95% CI –3.7
to –1.3, P < 0.0001) for GMRx2 versus telmisartan-
indapamide, –5.4 (–6.8 to –4.1,
P < 0.0001) versus telmisartan-amlodipine
and –4.4 (–5.8 to –3.1, P < 0.0001) versus
amlodipine-indapamide.

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