FDA Approves First, Only Single-Pill Triple Combination for Treatment of Hypertension

A novel single-pill combination of telmisartan, amlodipine, and indapamide (GMRx2, Widaplik; George Medicines) has been approved by the FDA for the treatment of adult patients with hypertension, including as an initial treatment and to lower blood pressure. The decision, based on 2 international phase 3 trials, represents the first and only FDA-approved triplet combination therapy.

Doctor measuring patient's blood pressure | Image Credit: © grinny - stock.adobe.com

“I am very excited and pleased to have [GMRx2] approved for the treatment of hypertension in the US. Single-pill combination antihypertensive therapy has great potential to improve hypertension control in the United States and worldwide,” Paul Whelton, MD, show Chwan chair of Global Public Health at Tulane University, New Orleans, Louisiana, and past president of the World Hypertension League, said in a press release. “Most patients with hypertension need multiple therapies to achieve their blood pressure goals. The new dose options available with [GMRx2] offer a treatment regimen that could benefit a broad range of patients, including those just starting treatment.”¹

GMRx2 is comprised of telmisartan, an angiotensin II receptor blocker; amlodipine, a dihydropyridine calcium channel blocker; and indapamide, a thiazide-like diuretic. In the GMRx2_ACT (NCT04518293) and GMRx2_PCT (NCT04518306) trials, telmisartan, amlodipine, and indapamide showed superior capabilities in reducing blood pressure (BP) and improved BP control rates when compared with dual therapy and placebo.^1-3

In GMRx2_ACT, GMRx2 was compared with the dual combinations of 20 mg of telmisartan with 2.5 mg of amlodipine, 20 mg of telmisartan with 1.25 mg of indapamide, or 2.5 mg of amlodipine with 1.25 mg of indapamide. At week 6, doses were doubled in all groups. The primary end point was mean change in home systolic BP (SBP) from baseline to week 12, and the primary safety outcome was treatment discontinuation due to an adverse event (AE) from baseline to week 12, with secondary end points including differences in clinic and home blood pressure levels and control rates.³

At week 12, patients receiving GMRx2 achieved a mean home SBP of 126 mm Hg, which was lower compared with each of the dual combinations: –2·5 (95% CI –3.7 to –1.3, P < .0001) versus telmisartan–indapamide; –5.4 (–6.8 to –4.1, P < .0001) versus telmisartan–amlodipine; and –4.4 (–5·8 to –3·1, P < .0001) versus amlodipine–indapamide. Clinical BP was also superior in the GMRx2 group (74%) compared with the other dual combinations (range 53% to 61%).³

In the GMRx2_PCT trial, investigators assessed 295 patients with hypertension who were randomized 2:2:1 to receive either GMRx2 ¼ dose (telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg), GMRx2 ½ dose (telmisartan 20 mg; amlodipine 2.5 mg; indapamide 1.25 mg), or placebo. The primary end point was change in SBP from randomization to week 4. Safety was also a key outcome measured.⁴

At week 4, BP control (less than 140/90 mm Hg) in the GMRx2 ¼ dose group was 37%, compared with 65% in the GMRx2 ½ dose group and 70% for placebo (both doses P < 0.001 vs placebo). The safety profile of GMRx2 at both the ¼ and ½ doses was favorable, with few reports of treatment discontinuation due to an adverse event (AE). There were no reported AEs in the GMRx2 ¼ dose arm and 6 (5.1%) in the ½ dose arm, compared with 1 in the placebo group.⁴

“Data show that most patients with hypertension will require 2 or more medicines to bring their blood pressure under control,” Mark Mallon, chief executive officer of George Medicines, said in a press release. “[GMRx2] can provide patients with hypertension, including those who are starting treatment, with a different approach to control their blood pressure. With its triple combination efficacy, established safety profile, good tolerability, and its availability in a single pill, [GMRx2] has the potential to address key challenges in current hypertension treatment approaches.”¹

REFERENCES

1. George Medicines announces FDA approval of WIDAPLIK™ (telmisartan, amlodipine and indapamide), a new single pill combination treatment for hypertension in adults, including initial treatment. Globe Newswire. June 9, 2025. Accessed June 9, 2025. https://www.globenewswire.com/news-release/2025/06/09/3095734/0/en/George-Medicines-announces-FDA-approval-of-WIDAPLIK-telmisartan-amlodipine-and-indapamide-a-new-single-pill-combination-treatment-for-hypertension-in-adults-including-initial-treat.html

2. Efficacy and safety of GMRx2 compared to dual combinations for the treatment of hypertension (GMRx2_ACT). Updated June 3, 2025. Accessed June 9, 2025. https://clinicaltrials.gov/study/NCT04518293

3. Efficacy and safety of GMRx2 compared to placebo for the treatment of hypertension (GMRx2_PCT). Updated June 3, 2025. Accessed June 9, 2025. https://clinicaltrials.gov/study/NCT04518306?term=NCT04518306&rank=1

4. Rodgers A, Salam A, Schutte A, et al. Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, amlodipine and indapamide, compared with dual combinations for treatment of hypertension: a randomised, double-blind, active-controlled, international clinical trial. The Lancet. October 19, 2024. doi: 10.1016/S0140-6736(24)01744-6

5. Rodgers A, Salam A, Schutte A, et al. Efficacy and safety of a novel low-dose triple single-pill combination compared with placebo for initial treatment of hypertension. JACC. December 2024. doi: 10.1016/j.jacc.2024.08.025