Telmisartan-based monotherapy and combination regimens for blood pressure control in adults with hypertension: a systematic review, meta-analysis, and GRADE assessment

Abstract

Purpose

To evaluate the efficacy, safety, and certainty of evidence for telmisartan-based antihypertensive regimens in adults with hypertension.

Methods

This systematic review and meta-analysis followed PRISMA 2020. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL were searched from inception to 2026. Eligible studies enrolled adults with hypertension and compared telmisartan monotherapy or telmisartan-containing combinations with placebo, usual care, non-telmisartan antihypertensive agents, or alternative telmisartan-based regimens. Continuous outcomes were pooled as mean differences (MDs) and dichotomous outcomes as risk ratios (RRs), both with 95% confidence intervals (CIs), using random-effects models, with additional subgroup analyses conducted by comparator type. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated using GRADE.

Results

Twenty-five included reports (24 unique trials, since two reports present secondary outcomes from the same underlying trial) involving 6,521 participants were included, spanning placebo-controlled, usual-care-controlled, active-comparator, and telmisartan-combination-versus-telmisartan-monotherapy designs. Telmisartan-based therapy significantly reduced office systolic blood pressure (MD − 6.39 mm Hg; 95% CI − 7.86 to − 4.93; low certainty) and office diastolic blood pressure (MD − 4.88 mm Hg; 95% CI − 6.67 to − 3.09; low certainty), although the magnitude of effect was comparator-dependent. Based on only two trials, 24-h ambulatory systolic blood pressure (MD − 7.16 mm Hg; 95% CI − 10.61 to − 3.72) and ambulatory diastolic blood pressure (MD − 4.42 mm Hg; 95% CI − 6.36 to − 2.48) were reduced with moderate certainty. Telmisartan-based regimens improved blood pressure response (RR 1.68; 95% CI 1.31 to 2.16; moderate certainty) but not blood pressure control achievement (RR 1.44; 95% CI 0.92 to 2.24; very low certainty). Overall adverse events, dizziness, and headache were comparable (very low to low certainty), while edema was less frequent with telmisartan-based therapy (RR 0.33; 95% CI 0.15 to 0.73; moderate certainty).

Conclusion

Telmisartan-based regimens, particularly fixed-dose and multidrug combinations, effectively reduce office and ambulatory blood pressure and improve blood pressure response, with broadly comparable short-term safety and less edema. These effect sizes are comparator-dependent, and certainty of evidence for absolute blood pressure control achievement and for major adverse events is very low; heterogeneity, limited long-term data, and a predominance of Asian-population trials warrant cautious interpretation pending larger, higher-quality, and more geographically diverse confirmatory studies.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s12872-026-06488-z.

Introduction

Hypertension remains one of the leading modifiable contributors to cardiovascular, cerebrovascular, renal, and premature mortality worldwide. In 2024, an estimated 1.4 billion adults aged 30 to 79 years were living with hypertension globally, yet only approximately 320 million had their blood pressure adequately controlled [1]. Uncontrolled hypertension substantially increases the risk of stroke, myocardial infarction, heart failure, chronic kidney disease, vascular cognitive impairment, and premature death [1, 2], making effective, durable, and well-tolerated antihypertensive strategies central to reducing the global burden of cardiovascular disease.

Pharmacological therapy is a cornerstone of hypertension management, particularly among patients with confirmed hypertension or elevated cardiovascular risk. Contemporary guidelines recommend several first-line antihypertensive drug classes, including angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), calcium channel blockers, and thiazide or thiazide-like diuretics [2]. ARBs occupy an established role in blood pressure reduction through selective blockade of the renin–angiotensin–aldosterone system. They are widely used in clinical practice because they provide effective antihypertensive activity while avoiding tolerability problems associated with ACEi—particularly cough and the treatment discontinuation it drives [2, 3].

Telmisartan is a long-acting ARB indicated for hypertension, used as monotherapy or in combination [4]. Its terminal elimination half-life of approximately 24 h supports once-daily dosing and sustained antihypertensive activity across the full dosing interval [4]. That prolonged duration of action matters clinically: it may be particularly important for maintaining trough blood pressure control and improving 24-h ambulatory blood pressure profiles—outcomes increasingly recognized as more informative than isolated office readings [4, 5].

Earlier meta-analyses have evaluated telmisartan in selected comparative contexts. Against losartan, telmisartan appeared to offer better blood pressure control without increasing adverse events [6]; against candesartan, antihypertensive effects were broadly comparable [7]; and against valsartan, telmisartan was associated with greater reductions in both systolic and diastolic blood pressure in subgroup analyses, with no clear safety difference [8]. In comparisons with ACEi, telmisartan has consistently shown favorable tolerability, including fewer drug-related adverse events and lower cough burden [3].

The evidence base, however, remains fragmented. Prior reviews have largely focused on individual comparator classes, specific head-to-head comparisons, or ARB class-level rankings rather than a telmisartan-centered synthesis spanning placebo, no-treatment, and active-comparator trials [6–9]. More recent network meta-analyses have compared multiple ARBs or evaluated single-pill combination regimens, but these approaches can obscure direct pairwise estimates specific to telmisartan efficacy and safety across clinically distinct comparison groups [9, 10]. Uncertainties also persist around the influence of dose, regimen type, comparator class, follow-up duration, blood pressure measurement method, and the consistency of safety outcomes across trials.

An updated systematic review and pairwise meta-analysis is therefore warranted. This review synthesizes randomized evidence on changes in systolic and diastolic blood pressure, blood pressure response and control rates, ambulatory blood pressure outcomes, treatment discontinuation, and adverse events. Integrating efficacy and tolerability data across placebo and active comparators provides a clinically interpretable assessment of where telmisartan fits in contemporary hypertension management.

Methods

This systematic review and meta-analysis was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement [11]. The protocol was registered prospectively in PROSPERO under registration number CRD420261400208.

Eligibility criteria

Eligible studies were randomized controlled trials and comparative interventional studies enrolling adults aged 18 years or older with hypertension, defined using office, ambulatory, home, or guideline-based blood pressure criteria. Studies qualified if they assessed telmisartan monotherapy or telmisartan-containing dual or triple antihypertensive regimens, including fixed-dose or single-pill combinations with amlodipine, S-amlodipine, cilnidipine, azelnidipine, hydrochlorothiazide, chlorthalidone, or indapamide.

Eligible comparators included placebo, usual care, telmisartan monotherapy, non-telmisartan antihypertensive monotherapy or combination therapy, and alternative telmisartan-based combinations when the comparison assessed the effect of different partner drugs. Single-arm studies, case reports, case series, reviews, editorials, animal studies, pediatric studies, normotensive-only populations, and studies without extractable efficacy or safety data were excluded. Telmisartan chronotherapy studies were excluded from the main comparative synthesis unless the comparator was a different antihypertensive agent.

Information sources and search strategy

A systematic search of PubMed/MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL was performed from database inception to 5 May 2026. The strategy combined terms relating to telmisartan, hypertension, blood pressure, randomized trials, antihypertensive agents, and relevant comparators — including amlodipine, cilnidipine, azelnidipine, hydrochlorothiazide, chlorthalidone, indapamide, nebivolol, and ramipril — with no language restrictions. Reference lists of included studies and relevant reviews were screened for additional eligible records.

Study selection

Retrieved records were imported into reference-management software and deduplicated. Two reviewers independently screened titles and abstracts by using Rayyan software [12], then assessed potentially eligible articles at full text. Disagreements were resolved by discussion; unresolved conflicts were adjudicated by a third reviewer. Reasons for full-text exclusion were recorded, and the selection process was summarized in a PRISMA flow diagram.

Data extraction

Two reviewers independently extracted data using a standardized Excel sheet covering first author, publication year, country, study design, sample size, number of study arms, intervention and comparator arms, follow-up duration, and key findings. Baseline characteristics included age, sex, BMI, smoking status, diabetes mellitus, renal impairment, prior cardiovascular disease, and prior antihypertensive treatment. For continuous outcomes, mean change, standard deviation, and sample size were extracted per arm; for dichotomous outcomes, event counts and totals were recorded. Missing variance data were derived from available standard errors, confidence intervals, or p-values per standard meta-analytic guidance.

Outcomes

The primary outcome was change in office mean sitting systolic blood pressure from baseline to end of follow-up. When office measurements were unavailable, a predefined priority hierarchy applied: 24-h ambulatory, daytime, nighttime, home, and central systolic blood pressure, with central blood pressure analyzed separately where appropriate.

Secondary efficacy outcomes included change in diastolic blood pressure, blood pressure control and response rates, 24-h ambulatory blood pressure, daytime and nighttime blood pressure, home blood pressure, central systolic blood pressure, central pulse pressure, augmentation index, heart-rate-corrected augmentation index, and heart rate. Blood pressure response was defined per each trial's own protocol, generally as attainment of a prespecified reduction in systolic and/or diastolic blood pressure from baseline; blood pressure control was defined as attainment of a target office blood pressure threshold (typically < 140/90 mmHg, or a lower threshold in selected trials) at the end of follow-up. Because these definitions varied across trials, the two outcomes were analyzed separately and should not be treated as interchangeable. Safety outcomes covered any adverse events, treatment-emergent and treatment-related adverse events, serious adverse events, discontinuation due to adverse events, hypotension, dizziness, peripheral edema, hyperkalemia, increased serum creatinine, and acute kidney injury. Additional renal, metabolic, endothelial, inflammatory, and clinical outcomes were extracted when reported.

Risk-of-bias assessment

Risk of bias in randomized studies was assessed using the revised Cochrane Risk of Bias 2 tool across domains covering the randomization process, deviations from intended interventions, missing outcome data, outcome measurement, and selection of the reported result [13]. Each outcome was judged as low risk, some concerns, or high risk. Disagreements were resolved by consensus or third-reviewer adjudication. Although the eligibility criteria permitted non-randomized comparative interventional studies, all 25 included reports (24 unique trials) that ultimately met inclusion criteria were randomized trials; the ROBINS-I tool for non-randomized studies was therefore not required.

Statistical analysis

Meta-analyses were performed in R version 4.3.2 using the meta and/or metafor packages. Continuous outcomes were pooled as mean differences with 95% confidence intervals; dichotomous outcomes were pooled as risk ratios with 95% confidence intervals. Random-effects models were applied throughout, reflecting anticipated clinical and methodological heterogeneity across trials differing in telmisartan dose, combination regimen, comparator type, baseline cardiovascular risk, and follow-up duration. Statistical heterogeneity was quantified using I2, τ2, τ, and Cochran's Q. A two-sided p-value below 0.05 was considered statistically significant for pooled treatment effects.

Multi-arm studies were handled to avoid double-counting: intervention arms were combined, comparator groups split, or clinically distinct comparisons retained as appropriate. When multiple follow-up time points were available, the study-defined primary endpoint or the most clinically relevant time point was prioritized.

Subgroup, sensitivity, and publication-bias analyses

Because the eligible comparators spanned placebo, usual care, telmisartan monotherapy, non-telmisartan agents, and alternative telmisartan-based combinations, the overall pooled estimate for each efficacy outcome necessarily combines clinically distinct contrasts; comparator-defined subgroup estimates are therefore reported alongside the overall estimate and should be considered the primary basis for interpreting the magnitude of effect in a specific clinical context, consistent with the more granular subgroup analysis presented for systolic blood pressure change. Subgroup analyses were conducted by comparator type, intervention strategy, and blood pressure measurement method where sufficient data existed. Sensitivity analyses used leave-one-out procedures to assess the influence of individual studies on pooled estimates. Publication bias and small-study effects were evaluated with funnel plots and Egger's regression test when at least 10 comparisons were available; a contour-enhanced funnel plot was generated for systolic blood pressure change.

Certainty of evidence

The certainty of evidence for each major outcome was assessed using the GRADE approach, rated as high, moderate, low, or very low based on risk of bias, inconsistency, indirectness, imprecision, and publication bias [14]. Summary-of-findings tables covered the primary efficacy outcome, key secondary blood pressure outcomes, and major safety outcomes. Because the included evidence derives predominantly from randomized trials, initial certainty ratings started at high and were downgraded where important limitations were identified. For continuous outcomes, imprecision was downgraded when the 95% CI crossed a threshold of approximately 4–5 mmHg (a commonly used minimally important difference for office blood pressure change) or otherwise suggested a clinically ambiguous effect; for dichotomous outcomes, imprecision was downgraded when the 95% CI crossed the line of no effect and included both an appreciable benefit and an appreciable harm (approximating a doubling/halving convention), or when the total number of events or participants fell below the optimal information size.

Results

Study selection

Database searches retrieved 10,617 records across PubMed (1,471), Cochrane (1,052), Scopus (5,745), and Web of Science (2,349). Deduplication removed 3,537 records, leaving 7,080 for title and abstract screening. Of these, 7,046 were excluded. All 34 reports flagged for full-text review were retrieved; 9 were subsequently excluded (4 conference abstracts, 5 incomplete trials), yielding 25 included reports corresponding to 24 unique trials for the systematic review and meta-analysis — two reports (Gomaz 2025 and Gomaz 2026) present non-overlapping secondary outcomes from a single underlying trial rather than independent patient cohorts (Fig. 1).

Fig. 1.

PRISMA Flowchart

Study characteristics

The 25 included reports described 24 unique trials — Gomaz 2025 and Gomaz 2026 are companion secondary-outcome publications from the same underlying randomized trial (CTRI/2023/04/051878; telmisartan n = 34 vs. amlodipine/cilnidipine/ramipril n = 36), reporting non-overlapping outcome domains (inflammatory biomarkers and metabolic/vascular biomarkers, respectively) rather than independent patient cohorts — and enrolled 6,521 unique participants (counting this shared cohort once), published between 2021 and 2026, spanning settings in South Korea, India, Nigeria, Sri Lanka, and multinational trial networks. Designs varied across double-blind phase II/III trials, open-label randomized trials, active-controlled studies, placebo-controlled trials, and post-marketing comparative studies. Interventions included telmisartan monotherapy, telmisartan-based fixed-dose combinations, telmisartan-containing lipid-lowering combinations, and low-dose triple-pill regimens, compared against telmisartan monotherapy, other antihypertensives, alternative fixed-dose combinations, placebo, usual care, and standard-care protocols (Table 1).

Table 1.

Summary of the studies included

Study ID	Country	Study Design	Total no. of participants	Number of arms	Intervention arms	Comparator arms	Key findings
Ahn 2026	South Korea	Randomized, double-blind, phase III clinical trial	314	2	Telmisartan/amlodipine/chlorthalidone 20/2.5/6.25 mg once daily for 8 weeks	Telmisartan 40 mg once daily for 8 weeks	The low-dose triple single-pill combination was noninferior and superior to telmisartan monotherapy for mean sitting SBP reduction. Mean sitting DBP, BP normalization, and response rates also favored the combination, with comparable safety and no serious drug-related adverse events
Gomaz 2026	India	Prospective, randomized, active-controlled, parallel-group, open-label clinical trial	70	2	Telmisartan 40 mg once daily for 12 weeks	Other antihypertensives: amlodipine 5 mg, cilnidipine 10 mg, or ramipril 2.5 mg once daily	Telmisartan significantly improved insulin sensitivity (HOMA-IR) compared with other antihypertensive agents. ET-1 levels decreased similarly across groups, suggesting comparable vascular endothelial effects; no serious adverse events were reported
Jadhav 2026	India	Randomized, open-label, multicenter, post-marketing, parallel-arm study	188	2	Telmisartan 40/80 mg plus amlodipine 5 mg fixed-dose combination once daily for 12 months	Telmisartan 40/80 mg plus cilnidipine 10 mg fixed-dose combination once daily for 12 months	Both groups had significant UACR reductions and comparable eGFR and serum creatinine changes. SBP reduction was greater with telmisartan-amlodipine at 9 and 12 months, while DBP and safety outcomes were broadly similar
Lee 2026	South Korea	Randomized, double-blind, multicenter, therapeutic confirmatory, phase III clinical trial	235	3	Telmisartan 20 mg plus S-amlodipine 1.25 mg once daily for 8 weeks	Telmisartan 20 mg alone; S-amlodipine 1.25 mg alone	Telmisartan/S-amlodipine produced greater mean sitting SBP reductions than either monotherapy. Adverse-event rates were similar across groups, and no serious adverse events occurred
Lim 2026	South Korea	Prospective, randomized, multicenter, open-label, active-controlled trial	98	2	Nebivolol-based antihypertensive regimen for 12 weeks	Telmisartan-based antihypertensive regimen for 12 weeks	Both treatments reduced central SBP, but reduction was greater with telmisartan than nebivolol. Central pulse pressure decreased in both groups without a significant between-group difference; augmentation index improved more with telmisartan
Trident Research Group 2026	Multinational (12 countries)	Multinational, randomized, double-blind, placebo-controlled trial	1670	2	Low-dose triple single pill: telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg, in addition to standard care	Matching placebo, in addition to standard care	The triple pill reduced recurrent stroke after intracerebral hemorrhage versus placebo (4.6% vs 7.4%; HR, 0.61) and lowered mean follow-up SBP (127 vs 138 mm Hg). Major cardiovascular events were also lower, while treatment discontinuation because of adverse events was higher with the triple pill
Bafna 2025	India	Prospective, randomized, open-label, 12-week trial	225	2	Azelnidipine 16 mg plus telmisartan 40 mg fixed-dose combination	Amlodipine 5 mg plus telmisartan 40 mg fixed-dose combination	Both combinations significantly reduced SBP and DBP with no significant between-group BP difference. Azelnidipine-telmisartan produced a more favorable pulse-rate effect and less pedal edema, while UACR changes were small and comparable
Dixit 2025	India	Prospective, randomized, open-label, real-world, single-center study	327	3	Telmisartan 40 mg plus hydrochlorothiazide 12.5 mg	Amlodipine 5 mg plus hydrochlorothiazide 12.5 mg; ramipril 5 mg plus hydrochlorothiazide 12.5 mg	Telmisartan-hydrochlorothiazide was most effective for SBP reduction, while DBP reduction was comparable across groups. Reported ADRs were lowest in the telmisartan-hydrochlorothiazide group
Gomaz 2025	India	Randomized, open-label, parallel-group, active-controlled trial	70	2	Telmisartan 40 mg once daily for 12 weeks	Other antihypertensives: amlodipine, cilnidipine, or ramipril	Telmisartan showed numerical reductions in hsCRP, IL-6, and TNF-alpha, but between-group differences at 12 weeks were not statistically significant. The findings suggest a possible anti-inflammatory trend requiring larger confirmation
Lee 2024	South Korea	Randomized, double-blind, multicenter, therapeutic confirmatory, phase III clinical trial	100	3	Telmisartan 80 mg plus rosuvastatin 20 mg plus ezetimibe 10 mg for 8 weeks	Rosuvastatin 20 mg plus ezetimibe 10 mg; telmisartan 80 mg	Triple therapy significantly reduced mean sitting SBP versus rosuvastatin/ezetimibe and reduced LDL-C versus telmisartan alone. No serious adverse events occurred, and overall safety was comparable
Ojji 2024	Nigeria	Randomized, parallel-group, open-label, multicenter clinical trial	300	2	Low-dose triple-pill protocol: telmisartan/amlodipine/indapamide in quarter-, half-, and standard-dose options with accelerated up-titration	Standard-care Nigeria hypertension protocol starting with amlodipine 5 mg	The triple-pill protocol achieved greater home SBP reduction and higher home and clinic BP-control rates than standard care. No participants discontinued trial treatment because of adverse events
Park 2024	South Korea	Multicenter, randomized, double-blind, phase IV trial	252	2	Telmisartan 40 mg plus amlodipine 5 mg plus rosuvastatin 10 mg fixed-dose combination	Amlodipine 5 mg plus atorvastatin 10 mg fixed-dose combination	Telmisartan/amlodipine/rosuvastatin produced greater mean sitting SBP and LDL-C reductions than amlodipine/atorvastatin. No severe adverse events were observed
Rodgers 2024	International: Australia, Nigeria, Sri Lanka, United States, United Kingdom	International, randomized, double-blind, placebo-controlled, parallel-group trial	295	3	GMRx2 quarter dose: telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg; GMRx2 half dose: telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg	Placebo	Both low-dose triple single-pill combinations produced clinically relevant home and clinic BP reductions versus placebo and improved clinic BP control at week 4. Tolerability was generally good, although discontinuations were numerically higher with the half-dose formulation
Wander 2024	India	Multicenter, randomized, double-blind, parallel-group, comparative, prospective phase III clinical study	264	2	Telmisartan 40 mg plus bisoprolol 5 mg fixed-dose combination for 12 weeks	Telmisartan 40 mg plus metoprolol succinate ER 50 mg fixed-dose combination for 12 weeks	Both fixed-dose combinations reduced seated SBP and DBP and had comparable efficacy, safety, and tolerability. SBP reduction was numerically and statistically greater with telmisartan-bisoprolol, and no serious adverse events or deaths were reported
Cho 2023	South Korea	Multicenter, double-blind, active-controlled, randomized, phase III trial	374	2	Telmisartan/amlodipine/chlorthalidone, up-titrated from 40/5/12.5 mg to 80/5/25 mg	Telmisartan/amlodipine, up-titrated from 40/5 mg to 80/5 mg	Triple therapy reduced mean sitting SBP more than dual therapy and achieved higher target BP and responder rates. No serious adverse events or adverse-event discontinuations were reported
Dash 2023	India	Prospective, randomized, active-controlled, open-label, parallel-group clinical trial	50	2	Azilsartan 40 mg plus amlodipine 5 mg once daily for 12 weeks	Telmisartan 40 mg plus amlodipine 5 mg once daily for 12 weeks	Azilsartan-amlodipine was noninferior to telmisartan-amlodipine for BP response. Both groups had significant reductions in SBP, DBP, and hsTnI, with similar tolerability
Sawant 2023	India	Prospective, randomized, open-label, single-center study using ambulatory BP monitoring	40	2	Telmisartan 40 mg once daily for 56 days (80 mg if needed)	Cilnidipine 10 mg once daily for 56 days (20 mg if needed)	Both telmisartan and cilnidipine were effective and well tolerated in newly diagnosed stage I hypertension. Telmisartan provided more sustained 24-h BP control, with advantages in the last 6 h of the dosing interval and early morning BP reduction
Song 2023	South Korea	Multicenter, randomized, three-arm, double-blind, placebo-controlled phase III trial	181	3	Ezetimibe 10 mg/rosuvastatin 20 mg plus telmisartan 80 mg once daily for 8 weeks	Ezetimibe 10 mg/rosuvastatin 20 mg; telmisartan 80 mg	The coadministered ezetimibe-rosuvastatin plus telmisartan regimen significantly reduced mean sitting SBP versus ezetimibe-rosuvastatin and significantly reduced LDL-C versus telmisartan. No serious adverse events were observed
Gnanenthiran 2022	Sri Lanka	Post-hoc/secondary analysis of an open-label randomized controlled trial (TRIUMPH)	700	2	Low-dose triple pill: telmisartan 20 mg, amlodipine 2.5 mg, chlorthalidone 12.5 mg; up-titration available	Usual care	Participants with diabetes had smaller observed BP reductions than those without diabetes in both triple-pill and usual-care groups. The triple pill still achieved greater BP reduction than usual care overall
Kim 2022	South Korea	Multicenter, randomized, parallel-group comparative phase IV clinical trial with open-label extension	217	2	Telmisartan 40 mg plus S-amlodipine 2.5 mg for 8 weeks	Telmisartan 80 mg for 8 weeks	Telmisartan/S-amlodipine achieved greater reductions in 24-h mean ambulatory SBP and DBP and improved daytime, nighttime, morning, and clinic BP outcomes compared with telmisartan 80 mg. Safety was comparable
Lee 2022	South Korea	24-week randomized, open-label, parallel, multicenter trial	99	2	Telmisartan 40/80 mg plus rosuvastatin 20 mg	Amlodipine 5/10 mg plus rosuvastatin 20 mg	Telmisartan did not significantly reduce HOMA-IR compared with amlodipine. However, fasting glucose, regression from impaired fasting glucose to euglycemia, and new-onset diabetes outcomes favored telmisartan
Meher 2022	India	Prospective, randomized, active-controlled, open-label, parallel-group clinical trial	50	2	Azilsartan 40 mg once daily for 12 weeks	Telmisartan 40 mg once daily for 12 weeks	Azilsartan and telmisartan had comparable effects on insulin resistance, leptin, adiponectin, and BP reduction. No significant between-group differences were observed; adverse effects were mild and comparable
Ram 2022	India	Investigator-initiated, prospective, randomized, open-label clinical study	96	2	Telmisartan 40 mg plus amlodipine 5 mg daily for 8 weeks	Telmisartan 40 mg plus cilnidipine 10 mg daily for 8 weeks	Both combinations significantly reduced office BP to below the < 130/80 mm Hg target. Telmisartan-amlodipine improved central aortic BP and pulse wave velocity, whereas telmisartan-cilnidipine improved augmentation index
Sung 2022	South Korea	Randomized, double-blind, parallel, phase II clinical trial	176	7	Low-dose triple combinations of telmisartan/amlodipine/chlorthalidone: quarter dose (10/1.25/3.125 mg), third dose (13.333/1.667/4.167 mg), and half dose (20/2.5/6.25 mg) for 8 weeks	Placebo; amlodipine 5 mg; amlodipine 10 mg; telmisartan 80 mg	Low-dose triple combinations improved BP-lowering efficacy versus placebo, with quarter- and half-dose regimens also outperforming amlodipine 5 mg and showing effects comparable to amlodipine 10 mg and telmisartan 80 mg. No specific safety concerns were identified
Bhardwaj 2021	India	Open-label, randomized, comparative, intention-to-treat, prospective study	200	4	Amlodipine 2.5–10 mg/day; ramipril 2.5–10 mg/day; telmisartan 40–80 mg/day; ramipril 1.25–5 mg/day plus telmisartan 20–40 mg/day	Not applicable; four active treatment arms	All regimens significantly reduced SBP and DBP and improved diabetes-related quality-of-life scores, with no significant between-group efficacy differences. Amlodipine and telmisartan were better tolerated than ramipril-containing therapy because of less dry cough

Abbreviations: ADR adverse drug reaction, AE adverse event, BP blood pressure, DBP diastolic blood pressure, ER extended release, ET-1 endothelin-1, FDC fixed-dose combination, HOMA-IR homeostatic model assessment for insulin resistance, HR hazard ratio, IL-6 interleukin-6, LDL-C low-density lipoprotein cholesterol, MACE major adverse cardiovascular events, SBP systolic blood pressure, SPC single-pill combination, UACR urine albumin-creatinine ratio

Participants were generally middle-aged to older adults (mean ages ranging from the early 40 s to late 60 s), with a predominantly male distribution, though sex ratios varied across arms. BMI, smoking status, diabetes, renal impairment, prior cardiovascular disease, and previous antihypertensive treatment were inconsistently reported. Several trials specifically enrolled high-risk populations — patients with diabetes, chronic kidney disease, coronary artery disease, prior intracerebral hemorrhage, or established antihypertensive treatment histories (Table 2).

Table 2.

Baseline characteristics of the included studies

Study ID	Group	Sample size	Age, mean (SD)	Male n (%)	BMI, mean (SD)	Current smokers n (%)	Diabetes mellitus n (%)	Renal impairment n (%)	Prior CVD n (%)	Prior antihypertensive treatment n (%)
Ahn 2026	TEL/AML/CHTD 20/2.5/6.25 mg	151	57 (14)	106 (70)	26 (4)	29 (19)	NA	NA	NA	127 (84)
	TEL 40 mg	155	60 (12)	109 (70)	26 (3)	37 (24)	NA	NA	NA	129 (83)
Gomaz 2026	Telmisartan	34	56 (8)	15 (44.1)	NA	NA	34 (100)	NA	NA	NA
	Other antihypertensives	36	53 (9)	17 (47.2)	NA	NA	36 (100)	NA	NA	NA
Jadhav 2026	Telmisartan + amlodipine FDC	94	52.5 (10.85)	52 (55.3)	27.1 (4.07)	NA	NA	94 (100)	NA	94 (100)
	Telmisartan + cilnidipine FDC	94	54.7 (10.36)	51 (54.3)	27.1 (5.13)	NA	NA	94 (100)	NA	94 (100)
Lee 2026	Tel/S-Amlo	77	57.09 (11.80)	47 (61.04)	NA	NA	NA	NA	NA	NA
	Tel	78	57.55 (13.45)	43 (55.13)	NA	NA	NA	NA	NA	NA
	S-Amlo	79	56.15 (13.76)	45 (56.96)	NA	NA	NA	NA	NA	NA
Lim 2026	Nebivolol	49	63.7 (8)	23 (46.9)	NA	3 (6.1)	6 (12.2)	NA	NA	NA
	Telmisartan	49	60.3 (12)	28 (57.1)	NA	10 (20.4)	13 (26.5)	NA	NA	NA
TRG 2026	Triple pill	833	57.5 (11.2)	558 (67.0)	NA	43 (5.2)	181 (21.7)	0	ICH 833 (100); CAD 47 (5.6)	740 (88.8)
	Placebo	837	58.0 (11.5)	549 (65.6)	NA	47 (5.6)	188 (22.5)	0	ICH 837 (100); CAD 55 (6.6)	740 (88.4)
Bafna 2025	Azelnidipine + telmisartan	115	53.5 (12.2)	63 (54.8)	27.9 (4.40)	NA	NA	NA	NA	NA
	Amlodipine + telmisartan	110	54.7 (11.2)	59 (53.6)	27.6 (3.88)	NA	NA	NA	NA	NA
Dixit 2025	Amlodipine + HCTZ	109	56.11 (12.54)	53 (48.6)	NA	NA	0 (excluded)	0 (excluded)	0 (significant CVD excluded)	0 (0)
	Telmisartan + HCTZ	111	56.81 (12.94)	51 (45.9)	NA	NA	0 (excluded)	0 (excluded)	0 (significant CVD excluded)	0 (0)
	Ramipril + HCTZ	107	62.19 (12.91)	51 (47.7)	NA	NA	0 (excluded)	0 (excluded)	0 (significant CVD excluded)	0 (0)
Gomaz 2025	Telmisartan	34	56 (8)	15 (44.1)	NA	NA	34 (100)	NA	NA	NA
	Other antihypertensives	36	53 (9)	17 (47.2)	NA	NA	36 (100)	NA	NA	NA
Lee 2024	TRE	33	63.64 (10.65)	26 (78.79)	26.19 (2.76)	NA	NA	NA	NA	28 (84.85)
	RE	31	62.58 (10.76)	24 (77.42)	26.50 (3.50)	NA	NA	NA	NA	24 (77.42)
	T	32	60.75 (9.73)	22 (68.75)	25.73 (2.51)	NA	NA	NA	NA	27 (84.38)
Ojji 2024	Triple-pill protocol	150	52 (10)	69 (46)	28 (5)	1 (1)	2 (1.3)	0	NA	58 (39)
	Standard-care protocol	150	51 (9)	69 (46)	29 (6)	1 (1)	6 (4)	0	NA	57 (38)
Park 2024	Telmisartan/amlodipine/rosuvastatin	125	67.4 (11.3)	77 (61.6)	26.2 (2.8)	18 (14.4)	53 (42.4)	NA	CAD 98 (78.4)	NA
	Amlodipine/atorvastatin	127	68.2 (10.6)	73 (57.5)	26.3 (3.1)	20 (15.7)	57 (44.9)	NA	CAD 105 (82.7)	NA
Rodgers 2024	GMRx2 1/4	113	50 (12)	45 (40)	30.9 (6.0)	8 (7)	8 (7)	NA	NA	44 (39)
	GMRx2 1/2	119	51 (10)	58 (49)	30.4 (6.7)	12 (10)	10 (8)	NA	NA	61 (51)
	Placebo	63	51 (13)	27 (43)	30.0 (5.7)	4 (6)	3 (5)	NA	NA	33 (52)
Wander 2024	Telmisartan + metoprolol succinate ER	128	50.26 (8.98)	94 (71.21)	NA	NA	NA	0 (chronic renal failure excluded)	NA	128 (100)
	Telmisartan + bisoprolol	128	49.27 (10.35)	97 (73.48)	NA	NA	NA	0 (chronic renal failure excluded)	NA	128 (100)
Cho 2023	TEL/AML/CHTD	186	61.5 (10.6)	144 (77.4)	26.2 (3.5)	NA	39 (21.0)	CKD 26 (14.0)	NA	186 (100)
	TEL/AML	188	60.3 (10.8)	149 (79.3)	26.7 (3.5)	NA	51 (27.1)	CKD 28 (14.9)	NA	188 (100)
Dash 2023	Azilsartan + amlodipine	25	53.68 (8.86)	9 (36)	NA	NA	6 (20)	0 (excluded)	0 (serious CVD excluded)	25 (100)
	Telmisartan + amlodipine	25	52 (9.85)	15 (60)	NA	NA	6 (24)	0 (excluded)	0 (serious CVD excluded)	25 (100)
Sawant 2023	Telmisartan 40 mg	17	41.88 (11.16)	10 (58.8)	26.84 (5.15)	NA	NA	0 (chronic renal failure excluded)	0 (CAD excluded)	0 (newly diagnosed)
	Cilnidipine 10 mg	19	41.47 (12.69)	8 (42.1)	25.78 (4.41)	NA	NA	0 (chronic renal failure excluded)	0 (CAD excluded)	0 (newly diagnosed)
Song 2023	Eze/Ros 10/20 mg + Tel 80 mg	60	64.82 (10.07)	40 (66.67)	25.96 (3.18)	12 (20.00)	23 (38.33)	NA	CAD 11 (18.33)	NA
	Eze/Ros 10/20 mg	60	62.92 (8.72)	40 (66.67)	25.91 (3.36)	11 (18.33)	25 (41.67)	NA	CAD 15 (25.00)	NA
	Tel 80 mg	60	65.52 (10.63)	41 (68.33)	25.98 (2.70)	7 (11.67)	18 (30.00)	NA	CAD 9 (15.00)	NA
Gnanenthiran 2022	Usual care—no DM	243	55.0 (11.3)	108 (44.4)	26.1 (4.6)	14 (5.8)	0 (0)	CKD 1 (0.4)	CAD 13 (5.3)	NA
	Usual care—DM	108	58.2 (9.0)	47 (43.5)	26.2 (4.0)	5 (4.6)	108 (100)	CKD 2 (1.9)	CAD 9 (8.3)	NA
	Triple pill—no DM	237	55.0 (11.5)	103 (43.5)	25.9 (4.7)	15 (6.3)	0 (0)	CKD 3 (1.3)	CAD 13 (5.5)	NA
	Triple pill—DM	112	59.5 (10.2)	39 (34.8)	25.8 (4.2)	5 (4.5)	112 (100)	CKD 4 (3.6)	CAD 17 (15.2)	NA
Kim 2022	Telmisartan 40/S-amlodipine 2.5	96	63.5 (12.5)	59 (61.5)	NA	NA	33 (34.4)	CKD 18 (18.8)	NA	> = 2 drugs 85 (88.5)
	Telmisartan 80	88	62.7 (10.9)	46 (52.3)	NA	NA	32 (36.4)	CKD 16 (18.2)	NA	> = 2 drugs 79 (89.8)
Lee 2022	Telmisartan-statin	48	61.0 (8.8)	39 (81.2)	25.7 (2.9)	11 (22.9)	0 (0)	NA	CAD 48 (100)	NA
	Amlodipine-statin	51	59.3 (8.8)	38 (74.5)	26.0 (3.1)	16 (31.4)	0 (0)	NA	CAD 51 (100)	NA
Meher 2022	Telmisartan 40 mg	24	54.42 (7.83)	14 (58.3)	NA	NA	24 (100)	0 (excluded)	0 (serious CVD excluded)	NA
	Azilsartan 40 mg	23	53.09 (8.02)	13 (56.5)	NA	NA	23 (100)	0 (excluded)	0 (serious CVD excluded)	NA
Ram 2022	Telmisartan + amlodipine	48	48.3 (10.95)	20 (41.7)	29.4 (5.14)	NA	NA	NA	NA	27 (56.3)
	Telmisartan + cilnidipine	46	50.5 (9.71)	19 (41.3)	28.6 (4.58)	NA	NA	NA	NA	31 (67.4)
Sung 2022	Placebo	25	59.96 (13.19)	18 (72.00)	25.71 (3.29)	4 (16.00)	4 (16.00)	NA	NA	24 (96.00)
	TEL/AML/CHTD 10/1.25/3.125 mg	25	63.88 (8.45)	10 (40.00)	24.82 (3.07)	3 (12.00)	5 (20.00)	NA	NA	22 (88.00)
	TEL/AML/CHTD 13.333/1.667/4.167 mg	25	58.84 (10.15)	20 (80.00)	26.65 (3.50)	4 (16.00)	9 (36.00)	NA	NA	24 (96.00)
	TEL/AML/CHTD 20/2.5/6.25 mg	25	64.16 (6.68)	15 (60.00)	25.80 (4.18)	6 (24.00)	7 (28.00)	NA	NA	23 (92.00)
	Amlodipine 5 mg	26	61.65 (9.67)	18 (69.23)	25.55 (3.28)	7 (26.92)	7 (26.92)	NA	NA	22 (84.62)
	Amlodipine 10 mg	25	59.88 (10.82)	17 (68.00)	27.02 (3.62)	1 (4.00)	5 (20.00)	NA	NA	20 (80.00)
	Telmisartan 80 mg	25	58.12 (9.12)	17 (68.00)	25.97 (3.95)	8 (32.00)	3 (12.00)	NA	NA	23 (92.00)
Bhardwaj 2021	Amlodipine	50	51.75 (6.7)	31 (62)	NA	2 (4)	50 (100)	NA	NA	NA
	Ramipril	50	55.9 (11.2)	28 (56)	NA	2 (4)	50 (100)	NA	NA	NA
	Telmisartan	50	52 (10.3)	30 (60)	NA	2 (4)	50 (100)	NA	NA	NA
	Ramipril + telmisartan	50	51.1 (12)	28 (56)	NA	4 (8)	50 (100)	NA	NA	NA

Abbreviations: AML amlodipine, BMI body mass index, CAD coronary artery disease, CHTD chlorthalidone, CKD chronic kidney disease, CVD cardiovascular disease, DBP diastolic blood pressure, DM diabetes mellitus, FDC fixed-dose combination, HCTZ hydrochlorothiazide, NA not reported, RE rosuvastatin/ezetimibe, SBP systolic blood pressure, S-Amlo S-amlodipine, TEL/Tel telmisartan, TRE telmisartan/rosuvastatin/ezetimibe

Note: Gomaz 2025 and Gomaz 2026 are companion secondary-outcome reports of the same underlying randomized trial (CTRI/2023/04/051878; telmisartan n = 34 vs. amlodipine/cilnidipine/ramipril n = 36), reporting inflammatory biomarkers (hsCRP, IL-6, TNF-α) and metabolic/vascular biomarkers (HOMA-IR, endothelin-1), respectively, in the same 70 participants. Both are listed as separate rows for transparency and traceability to their respective publications, but the trial’s 70 participants are counted once in all participant totals reported in this review (24 unique trials across 25 included reports; 6,521 total participants)

Risk of bias assessment

Four studies were low risk overall, 19 showed some concerns, and 2 were high risk. The most common concerns involved the randomization process, deviations from intended interventions, missing outcome data, and selective reporting. Outcome measurement bias was less problematic, with most studies rated low risk in that domain. The two high-risk studies were flagged primarily for outcome measurement or selective reporting deficiencies (Fig. 2).

Fig. 2.

Quality assessment of the included studies according to the ROB-2 tool

Systolic blood pressure change

Telmisartan-based interventions reduced systolic blood pressure by a pooled mean difference of − 6.25 mm Hg (95% CI, − 7.75 to − 4.74; p < 0.0001; k = 24 comparisons across 18 trials), with moderate-to-substantial heterogeneity (I² = 63.6%).

Subgroup analysis demonstrated superiority of telmisartan combinations over telmisartan monotherapy (MD, − 4.68; 95% CI, − 7.08 to − 2.29) and over different telmisartan-based comparator combinations (MD, − 3.70; 95% CI, − 5.81 to − 1.58). Telmisartan monotherapy versus non-telmisartan monotherapy showed a nonsignificant trend favoring telmisartan (MD, − 2.64; 95% CI, − 5.63 to 0.34). Larger effects emerged from triple-pill and multidrug regimens, particularly against usual care, placebo, or non-telmisartan comparators. The subgroup differences test was significant, implicating treatment context and comparator type as drivers of heterogeneity (Fig. 3).

Fig. 3.

Subgroup forest plot of mean difference in systolic blood pressure change

Comparator-stratified sensitivity analysis

Because the overall pooled estimate for systolic blood pressure change combines clinically distinct treatment intensities, the 24 comparisons contributing to the primary analysis were additionally analyzed in two mutually exclusive groups: comparisons in which both arms were single-agent regimens (“telmisartan monotherapy vs. non-telmisartan monotherapy”), and comparisons in which at least one arm was a multidrug telmisartan-based combination (“telmisartan-based combination regimens vs. comparator regimens,” encompassing combination-vs-combination, add-on/intensification, and combination-vs-placebo/usual-care contrasts). Only four comparisons (Bhardwaj 2021 TEL vs. amlodipine; Bhardwaj 2021 TEL vs. ramipril; Meher 2022; Sawant 2023) met the strict monotherapy-vs-monotherapy definition; pooling these reproduced the monotherapy subgroup result reported above (MD − 2.65; 95% CI − 5.64 to 0.34; I² = 0%). The remaining 20 combination-involving comparisons pooled to a larger effect (MD − 6.92; 95% CI − 8.45 to − 5.38; I² = 64.7%), and a formal test for subgroup difference between the two groups reached statistical significance (p = 0.0499), supporting a genuine difference in effect size by treatment intensity (Figure S6, Figure S7). The same exercise could not be performed for diastolic blood pressure, because none of the 11 comparisons contributing to the diastolic blood pressure synthesis are monotherapy-vs-monotherapy contrasts; all 11 involve at least one combination arm, and their pooled estimate (MD − 4.88; 95% CI − 6.67 to − 3.09; I² = 82.9%) should therefore be interpreted as reflecting combination-level, not monotherapy-level, diastolic blood pressure effects (Figure S8). These comparator-stratified estimates, rather than the single overall pooled figure, are the recommended reference point for judging the expected effect size of a specific telmisartan-based treatment strategy.

Blood pressure measurement method contributing to the primary outcome

Of the 18 unique trials contributing to the primary systolic blood pressure synthesis, 15 used an office/clinic-based measurement (mean sitting or seated SBP), two used 24-h ambulatory blood pressure monitoring as the primary measure (Kim 2022, Sawant 2023), and one used home blood pressure (Ojji 2024), consistent with the predefined measurement-method hierarchy described in Methods 3.5.

Diastolic blood pressure change

The pooled mean difference for diastolic blood pressure was − 4.91 mm Hg (95% CI, − 6.89 to − 2.92; p < 0.0001; k = 11 comparisons across 7 trials), with substantial heterogeneity (I² = 82.9%) (Fig. 4). Leave-one-out sensitivity analysis confirmed robustness — sequentially removing each study produced recalculated estimates ranging from approximately − 4.03 to − 5.38 mm Hg, with the direction and significance preserved throughout (Figure S1).

Fig. 4.

Forest plot of mean difference in diastolic blood pressure change

Twenty-four-hour ambulatory blood pressure

Two studies reported ambulatory data. Telmisartan-based interventions reduced 24-h systolic blood pressure by − 7.16 mm Hg (95% CI, − 10.61 to − 3.72; p < 0.0001; I² = 0%) (Fig. 5A) and 24-h diastolic blood pressure by − 4.42 mm Hg (95% CI, − 6.36 to − 2.48; p < 0.0001; I² = 0%) (Fig. 5B). The absence of heterogeneity in both estimates is reassuring but should be interpreted cautiously: with only two contributing trials, an I² of 0% mainly reflects the limited number of comparisons available to detect between-study variability rather than a robust demonstration of consistency, and these ambulatory findings should not be weighted as heavily as outcomes supported by a larger evidence base.

Fig. 5.

Forest plots of 24-h ambulatory blood pressure changes. A 24-h SBP change B 24-h DBP change

Blood pressure response and control

Blood pressure response rates were significantly higher with telmisartan-based therapy (RR, 1.68; 95% CI, 1.31 to 2.16; p < 0.0001; I² = 0%) (Fig. 6A). Blood pressure control achievement did not reach significance (RR, 1.44; 95% CI, 0.92 to 2.24; p = 0.1096) (Fig. 6B), and heterogeneity was extreme (I² = 95.7%), likely reflecting divergent control definitions, follow-up durations, baseline risk profiles, and comparator regimens. Response and control are distinct constructs: response reflects attainment of a prespecified within-patient blood pressure reduction, whereas control reflects attainment of a fixed target threshold irrespective of baseline severity; the two outcomes are therefore not interchangeable, and the higher heterogeneity for control achievement partly reflects the wider range of control thresholds and baseline risk profiles used across the contributing trials.

Fig. 6.

Forest plots of blood pressure response and control A BP response rate B BP control achievement

A post hoc leave-one-out sensitivity analysis was performed for BP control achievement to identify the source of its extreme heterogeneity (I² = 95.7%). Omitting TRIDENT 2026 — a secondary-prevention trial in post-intracerebral-hemorrhage patients using a markedly lower target threshold (SBP < 130 mmHg) than the other three comparisons — reduced heterogeneity from I² = 93.2% to I² = 59.3% in the re-derived four-study model (RR 1.22; 95% CI 0.96 to 1.55). Conversely, omitting Wander 2024, whose near-null result (RR 1.02) pulls the pooled estimate toward the null, shifted the remaining estimate to a significant effect favoring telmisartan-based therapy (RR 1.58; 95% CI 1.20 to 2.07; I² = 65.7%). These two trials — differing from the others in population risk, target threshold, and comparator composition — jointly account for most of the inconsistency in this outcome (Figure S9).

Safety outcomes

Any adverse event rates were comparable between groups (RR, 1.00; 95% CI, 0.70 to 1.42; p = 0.9995), though heterogeneity was substantial (I² = 89.4%) (Fig. 7A); leave-one-out sensitivity analysis showed that this finding was not robust to the exclusion of a single trial — omitting Wander 2024 not only eliminated between-study heterogeneity (I² falling from 89.4% to 0%) but also shifted the pooled point estimate from RR 1.00 to RR 1.12 (95% CI, 1.00 to 1.25; p = 0.051), a borderline signal toward more adverse events with telmisartan-based therapy (Figure S2). Treatment-related adverse events trended nonsignificantly higher with telmisartan-based interventions (RR, 1.35; 95% CI, 0.97 to 1.87; p = 0.0708; I² = 0%) (Fig. 7B). Serious adverse events (RR, 0.70; 95% CI, 0.33 to 1.49; p = 0.3540) (Fig. 7C) and discontinuation due to adverse events (RR, 0.72; 95% CI, 0.39 to 1.33; p = 0.2878) were similarly nonsignificant (Fig. 7D).

Fig. 7.

Forest plots of safety outcomes. A Any adverse events B Treatment-related adverse events C Serious adverse events D Discontinuation due to adverse events E Edema

Edema was significantly less frequent with telmisartan-based regimens (RR, 0.33; 95% CI, 0.15 to 0.73; p = 0.0062; I² = 0%) (Fig. 7E). Dizziness (RR, 0.70; 95% CI, 0.30 to 1.63; p = 0.4038; I² = 0%) and headache (RR, 0.62; 95% CI, 0.23 to 1.68; p = 0.3455; I² = 0%) did not differ between arms (Figure S4 and Figure S5).

Publication bias

Funnel plot inspection for systolic blood pressure change revealed no strong evidence of small-study effects. Egger's regression test was nonsignificant (p = 0.686) (Figure S3). Given the clinical heterogeneity across comparisons, however, funnel plot interpretation warrants caution.

Certainty of evidence

GRADE assessment across efficacy and safety outcomes revealed considerable variation in evidence quality. For office systolic blood pressure change, certainty was low, driven by methodological concerns and moderate-to-substantial heterogeneity. Office diastolic blood pressure was similarly rated low, primarily due to risk-of-bias concerns and substantial heterogeneity. Both 24-h ambulatory outcomes — systolic and diastolic — were rated moderate; effects were consistent, but only two studies contributed data. Blood pressure response carried moderate certainty, supporting a reasonably reliable treatment benefit. Blood pressure control achievement was rated very low, undermined by risk-of-bias concerns, extreme heterogeneity, and imprecision, and should be interpreted with corresponding caution.

Safety outcome certainty was generally poor. Any adverse events, serious adverse events, and discontinuation due to adverse events were all rated very low, reflecting methodological concerns, sparse events, imprecision, and inconsistent adverse-event reporting across trials. Treatment-related adverse events, dizziness, and headache were supported by low-certainty evidence. Edema was the exception, rated moderate, indicating a more reliable reduction with telmisartan-based interventions. Taken together, the evidence is most robust for blood pressure response, 24-h ambulatory blood pressure reduction, and edema. Confidence in blood pressure control achievement and major safety endpoints remains substantially limited (Table S1).

Discussion

Telmisartan-based therapy provides a clinically meaningful antihypertensive benefit in adults with hypertension. Across 24 unique trials (25 included reports) involving 6,521 participants, telmisartan-based regimens significantly reduced office systolic blood pressure (SBP) and diastolic blood pressure (DBP), improved 24-h ambulatory SBP and DBP, and increased the likelihood of blood pressure response. Benefit was more consistent for blood pressure response and ambulatory blood pressure than for absolute blood pressure control, which did not reach statistical significance and showed substantial heterogeneity. Safety outcomes were broadly comparable between groups, while edema was significantly less frequent with telmisartan-based regimens. These findings support telmisartan-containing strategies as effective and generally well-tolerated options for hypertension management, particularly when used as fixed-dose or multidrug combinations.

The observed SBP reduction carries direct clinical weight. Data from the Blood Pressure Lowering Treatment Trialists' Collaboration show that each 5 mmHg reduction in SBP cuts major cardiovascular event risk by approximately 10%, regardless of baseline cardiovascular disease status [15]. Because this and most other evidence cited here relates to short-term surrogate blood pressure change rather than adjudicated long-term cardiovascular events, this extrapolation should be treated as supportive rather than definitive, and over-interpretation of surrogate BP reductions as guaranteed event reduction should be avoided. A related line of evidence, independent of telmisartan specifically, shows that intensive blood pressure lowering also reduces left ventricular hypertrophy, a structural marker of end-organ damage, lending broader plausibility to the idea that clinically meaningful BP reductions of the magnitude seen here can translate into structural as well as event-based benefit [16]. The pooled SBP reduction in this analysis is therefore likely clinically relevant, even accounting for variation in study design, comparator type, and baseline risk. Current WHO and ESC recommendations reinforce this by endorsing combination therapy—preferably single-pill combinations—to improve adherence, accelerate BP control, and reduce therapeutic inertia [2, 17].

The subgroup findings clarify where the benefit originates. Telmisartan monotherapy showed only a nonsignificant trend against non-telmisartan monotherapy, whereas telmisartan-based combinations produced clearer reductions against telmisartan monotherapy, non-telmisartan comparators, usual care, and placebo. This is biologically and clinically plausible: pairing renin–angiotensin system blockade with calcium-channel blockade and thiazide-like diuresis achieves greater BP reduction than dose escalation of a single agent. The low-dose triple-combination evidence within this review was particularly supportive. Sung et al. found that low-dose amlodipine/telmisartan/chlorthalidone improved BP lowering over 8 weeks compared with monotherapy without additional safety concerns [18], and Rodgers et al. (GMRx2 trial) showed that low-dose telmisartan/amlodipine/indapamide significantly reduced home and clinic SBP versus placebo with acceptable tolerability; this trial's office SBP and DBP data (half-dose arm) are included in the primary and secondary blood pressure syntheses above [19].

Further triple-pill data reinforce this interpretation. In the Nigerian trial by Ojji et al., a telmisartan/amlodipine/indapamide protocol achieved greater home SBP reduction and higher home BP control than standard care, with no treatment discontinuations due to adverse events [20]. TRIDENT extended the clinical relevance of this strategy to secondary stroke prevention after intracerebral hemorrhage: low-dose telmisartan/amlodipine/indapamide added to standard care reduced recurrent stroke and major cardiovascular events, though discontinuation was more frequent because of renal-function-related adverse events [21]. These data suggest that telmisartan-based low-dose multidrug therapy may not only improve BP metrics but may also translate into outcome benefits in high-risk populations. TRIDENT enrolled a high-risk secondary-prevention population with recent intracerebral hemorrhage, and its event-reduction findings should not be broadly extrapolated to primary hypertension management in lower-risk patients; it is presented here as supportive mechanistic and safety context rather than as direct evidence for the general hypertensive population studied in the remainder of this review. Because most studies in this meta-analysis reported short-term BP outcomes rather than long-term cardiovascular events, that conclusion warrants caution.

The ambulatory blood pressure findings add important nuance. Only two studies contributed to the 24-h ambulatory outcomes, yet both 24-h SBP and DBP were significantly reduced with no observed heterogeneity. Sawant et al. directly supports this: telmisartan was superior to cilnidipine for BP reduction during the final 6 h of the dosing interval and during early morning hours, while both drugs were well tolerated [22]. Morning BP surge and inadequate trough control are independently associated with increased cardiovascular risk, making telmisartan's approximately 24-h half-life a pharmacokinetically meaningful advantage.

Telmisartan-based therapy in patients with combined hypertension and dyslipidemia also showed benefit. Song et al. found that ezetimibe–rosuvastatin plus telmisartan significantly reduced mean seated SBP versus ezetimibe–rosuvastatin alone and significantly improved lipid parameters versus telmisartan alone, without a clear increase in serious adverse events [23]. Lee et al. similarly reported that telmisartan/rosuvastatin/ezetimibe improved both BP and lipid profiles compared with either rosuvastatin/ezetimibe or telmisartan alone [24]. These findings are particularly relevant for patients with clustered cardiometabolic risk factors, where BP control, lipid lowering, adherence, and pill burden must be managed simultaneously.

Not all comparator contexts produced large differences, and this matters for interpretation. Wander et al. compared telmisartan/bisoprolol with telmisartan/metoprolol in stage 1 and 2 hypertension and found comparable efficacy, tolerability, and safety between both combinations, with high target BP achievement in both arms [25]. When telmisartan-based therapy is compared with placebo, usual care, or monotherapy, the benefit is larger; when compared with another active telmisartan-based combination, the incremental difference is predictably smaller. This likely explains a substantial portion of the heterogeneity observed in SBP, DBP, and BP-control outcomes.

The safety profile was reassuring but should not be overstated. Overall adverse events, serious adverse events, treatment-related adverse events, and discontinuations due to adverse events were not significantly different between groups; however, nonsignificant differences with wide confidence intervals and low-to-very-low certainty evidence indicate only that no clear difference was detected, not that telmisartan-based regimens have been shown to be as safe as their comparators — a clinically important benefit or harm cannot be excluded for these outcomes. The "any adverse events" estimate in particular was not robust to the exclusion of a single trial: omitting Wander et al. eliminated essentially all between-study heterogeneity and shifted the pooled estimate toward a borderline signal of more adverse events with telmisartan-based therapy (RR 1.12; 95% CI, 1.00 to 1.25; p = 0.051). Wander et al. compared two beta-blocker-containing telmisartan combinations (telmisartan/bisoprolol versus telmisartan/metoprolol), the only beta-blocker-based comparison in this review; beta-blockers carry an adverse-event profile (e.g., bradycardia, fatigue) distinct from the calcium-channel-blocker- and diuretic-based regimens that dominate the other contributing trials, which may plausibly explain both its outlier contribution to heterogeneity and its influence on the pooled direction of effect. The overall "any adverse events" conclusion should therefore be regarded as sensitive to this single trial rather than as a settled finding. Edema was the clearest safety advantage, occurring significantly less often with telmisartan-based regimens—consistent with the known capacity of renin–angiotensin system blockade to mitigate calcium-channel blocker–related peripheral edema; this advantage is most directly interpretable in the context of the calcium-channel-blocker-containing comparator regimens from which it was largely derived, rather than as a generic property of telmisartan versus all comparators. GRADE certainty for most safety outcomes was low or very low because of sparse events, short follow-up, and inconsistent reporting. Edema was the exception, supported by moderate-certainty evidence. The most defensible safety conclusion is that no clear difference in overall tolerability was detected in the short term, with a probable reduction in edema in calcium-channel-blocker-containing comparisons, but stronger long-term data remain necessary before broader safety equivalence can be claimed.

Telmisartan's metabolic effects also warrant mention. Gomaz et al. (2026) reported that telmisartan significantly improved HOMA-IR versus other antihypertensive agents in patients with diabetes and hypertension, while endothelin-1 reduction was comparable between groups [26]. This supports the hypothesis that telmisartan may carry favorable metabolic effects beyond BP lowering, potentially linked to partial PPAR-γ agonist activity. A companion secondary-outcome report from the same trial (CTRI/2023/04/051878), Gomaz et al. (2025), additionally found numerically lower hsCRP, IL-6, and TNF-α with telmisartan versus other antihypertensive agents, although between-group differences did not reach statistical significance [27]; because this report and the HOMA-IR/ET-1 findings above derive from the same 70 participants rather than an independent cohort, we treat them as complementary readouts of a single trial rather than corroborating evidence from two studies, and have counted this trial's participants only once in the totals reported throughout this review (see Table 1 note). Together, the two reports are mechanistically coherent with telmisartan's partial PPAR-γ agonism, which has been linked to both insulin-sensitizing and anti-inflammatory activity, and offers a plausible unifying explanation for the cardiometabolic signals observed across the telmisartan/statin combination trials discussed above. This should be treated as exploratory: many included trials were not designed to evaluate hard metabolic, renal, or cardiovascular outcomes, and several used surrogate markers, small samples, or short follow-up.

This review included recent randomized and comparative evidence across diverse settings, evaluated both office and ambulatory BP outcomes, assessed clinically relevant safety endpoints, and incorporated GRADE certainty assessment. The inclusion of low-dose triple-pill trials, cardiometabolic fixed-dose combination trials, and active comparator studies provides a broad picture of telmisartan-based therapy across real-world therapeutic contexts. The breadth of included interventions is also a limitation. Telmisartan monotherapy, telmisartan/CCB combinations, triple therapy with a diuretic, beta-blocker combinations, and telmisartan/lipid-lowering combinations were pooled under the wider category of telmisartan-based therapy. The overall pooled estimates reported for each efficacy outcome therefore largely reflect differences in treatment intensity and co-administered drugs rather than a single common effect of telmisartan itself, and should not be interpreted as a unified telmisartan-specific effect size; readers seeking the effect for a specific clinical contrast (e.g., telmisartan-based combination versus telmisartan monotherapy, or triple-pill versus usual care) should instead refer to the corresponding comparator-defined subgroup estimate in Fig. 3. The results should therefore not be interpreted as proving telmisartan alone superior to all antihypertensives—rather, that telmisartan-containing regimens, particularly fixed-dose and multidrug combinations, are effective BP-lowering strategies. A comparator-stratified analysis of the primary and secondary blood pressure outcomes, separating strict monotherapy-vs-monotherapy comparisons from all combination-involving comparisons, is reported above and supports this interpretation: the monotherapy-only estimate was smaller and nonsignificant (MD − 2.65; 95% CI − 5.64 to 0.34), while the combination-involving estimate was larger and significant (MD − 6.92; 95% CI − 8.45 to − 5.38), and the formal test for subgroup difference reached statistical significance (p = 0.0499). A fully comparator-stratified restructuring of every remaining outcome (safety endpoints, BP response and control) was beyond the scope of the present analysis but is a priority for future updates of this review.

Several additional limitations apply. Heterogeneity was substantial for office BP and BP-control outcomes, likely reflecting differences in baseline BP, treatment duration, comparator intensity, control definitions, and patient risk profiles. Many studies had open-label designs or raised concerns in risk-of-bias domains, which lowered certainty. Follow-up was generally short, limiting inference about long-term cardiovascular, renal, or metabolic outcomes; the predominance of short-follow-up trials also made it impossible to evaluate mortality or hard cardiovascular events within this review. The literature search covered PubMed/MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL but did not include a trial registry (e.g., ClinicalTrials.gov) or other gray-literature search; for a widely used generic drug such as telmisartan, unpublished or registry-only trials, including null or negative results, represent a real publication-bias risk that Egger's test alone cannot fully address. Telmisartan chronotherapy studies were excluded from the main comparative synthesis unless the comparator was a different antihypertensive agent, consistent with evidence that dosing-time itself has limited independent effect on cardiovascular outcomes [28]. Safety outcomes were inconsistently reported and often underpowered; in particular, although Rodgers et al. (GMRx2) reports complete safety data (treatment discontinuation, adverse events of special interest, serious adverse events, and electrolyte abnormalities for both dose arms), these were not extracted into the safety synthesis and are not reflected in the pooled safety estimates above; incorporating them is a priority for a future update. Finally, many studies were conducted in Asian populations, with fewer data from African, European, or multinational settings; this, combined with the generally short follow-up, limits generalizability and precludes conclusions about mortality or major cardiovascular events, though the inclusion of Nigerian and multinational triple-pill trials improves generalizability.

Conclusion

Telmisartan-based therapy significantly improves systolic and diastolic blood pressure, 24-h ambulatory blood pressure, and blood pressure response in adults with hypertension, with broadly comparable short-term safety and a lower risk of edema. The strongest evidence supports benefits in BP response, ambulatory BP reduction, and edema reduction. The nonsignificant effect on absolute BP control should be interpreted cautiously given extreme heterogeneity and variable control definitions. Telmisartan-based regimens appear most useful when delivered as fixed-dose or low-dose multidrug combinations, particularly in patients requiring sustained 24-h BP control or management of multiple cardiometabolic risk factors. Future large, longer-term trials should clarify whether these BP improvements translate into fewer cardiovascular and renal events and identify which patient subgroups derive the greatest net benefit.

Abbreviations

ACEi

Angiotensin-converting enzyme inhibitor

ADR

Adverse drug reaction

AE

Adverse event

AKI

Acute kidney injury

RB

Angiotensin II receptor blocker

BP

Blood pressure

CCB

Calcium channel blocker

CENTRAL

Cochrane Central Register of Controlled Trials

CI

Confidence interval

CKD

Chronic kidney disease

CVD

Cardiovascular disease

DBP

Diastolic blood pressure

eGFR

Estimated glomerular filtration rate

ESC

European Society of Cardiology

ET-1

Endothelin-1

FDC

Fixed-dose combination

GRADE

Grading of Recommendations Assessment, Development and Evaluation

HOMA-IR

Homeostatic model assessment of insulin resistance

HR

Hazard ratio

hsCRP

High-sensitivity C-reactive protein

IL

Interleukin

LDL-C

Low-density lipoprotein cholesterol

MD

Mean difference

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PROSPERO

International Prospective Register of Systematic Reviews

RCT

Randomized controlled trial

RoB 2

Revised Cochrane risk-of-bias tool for randomized trials

RR

Risk ratio

SAE

Serious adverse event

SBP

Systolic blood pressure

UACR

Urinary albumin-to-creatinine ratio

WHO

World Health Organization

Authors’ contributions

BAA, MSF, and YN contributed to the conceptualization and design of the study. MSAA, ASMA, and SAA contributed to the literature search, study screening, and data extraction. SEE, MSF, and YN contributed to data verification, risk-of-bias assessment, and interpretation of the findings. YN performed the statistical analysis, prepared the meta-analytic figures, and contributed to the GRADE assessment. BAA drafted the initial manuscript. MSF and YN critically revised the manuscript for important intellectual content. YN supervised the study and coordinated the overall research workflow. All authors reviewed, edited, and approved the final version of the manuscript and agreed to be accountable for all aspects of the work.

Funding

This research work was funded by the Deanship of Scientific Research at Northern Border University, Arar, KSA, through project number NBU-FFR-2026–78-04.

Data availability

All data generated or analysed during this study are included in this published article and its supplementary information files. The extracted datasets supporting the meta-analysis are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable. This systematic review and meta-analysis used previously published aggregate data and did not involve new studies with human participants or animals conducted by any of the authors.

Consent for publication

Not applicable. This manuscript does not contain any individual person’s data.

Competing interests

The authors declare no competing interests.