Irbesartan

What it is

Irbesartan is a synthetic small-molecule angiotensin II receptor blocker (ARB) taken as a tablet. It binds the AT1 angiotensin II receptor and blocks the vasoconstricting and aldosterone-releasing actions of angiotensin II; the label states it has more than 8500-fold greater affinity for AT1 than for AT2 and no agonist activity. Unlike an ACE inhibitor it does not inhibit angiotensin-converting enzyme, which is why it does not produce the ACE-inhibitor cough. In the United States it is approved for high blood pressure and for diabetic kidney disease in type 2 diabetes.

What the research says

The strongest evidence is for the kidney. Two placebo-controlled randomised trials in type 2 diabetes (IDNT, 1715 patients; IRMA-2, 590 patients) showed irbesartan slowed kidney damage independently of blood pressure, with absolute benefits of roughly 6 to 10 percentage points over 2 to 2.6 years. Neither trial showed any reduction in death. For blood pressure, a Cochrane review of 46 trials puts the class effect at about -8/-5 mmHg, and blood pressure lowering itself is linked to fewer cardiovascular events in a 123-trial meta-analysis. Where irbesartan has been tested on hard outcomes outside kidney disease it has failed: it did not improve outcomes in heart failure with preserved ejection fraction (I-PRESERVE, 4128 patients) or in atrial fibrillation (ACTIVE I, 9016 patients). Harms are real and measurable: in IDNT 18.6% of irbesartan patients had potassium above 6 mEq/L versus 6.0% on placebo.

Evidence grade: Well established.

How it works

Drug class: Angiotensin II receptor blocker (ARB, AT1-receptor antagonist)

Angiotensin II is the hormone that narrows blood vessels and tells the adrenal gland to release aldosterone, which makes the body hold on to salt and water. Irbesartan sits on the AT1 receptor so angiotensin II cannot act there. Blood vessels relax, blood pressure falls, and pressure inside the kidney's filters drops, which is thought to be why it slows protein leak and kidney scarring. (Source 1)

Boxed warning

When pregnancy is detected, discontinue AVAPRO as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].

(Source 2)

What it is used for

• Irbesartan lowers blood pressure by roughly 8/5 mmHg at maximum dose as a class effect, and a 123-trial meta-analysis found each 10 mmHg fall in systolic pressure went with a 20% lower risk of major cardiovascular events. The approval rests on blood-pressure trials, not on an irbesartan-specific outcome trial in uncomplicated hypertension. Evidence: established. (Source 3)
• In IDNT, irbesartan 300 mg daily cut the composite of doubled creatinine, end-stage kidney disease or death from 39.0% to 32.6% over a mean 2.6 years. In IRMA-2, progression to overt nephropathy fell from 14.9% to 5.2% over two years at 300 mg. Neither trial reduced death, and hyperkalaemia was three times more common than on placebo. Evidence: established. (Source 4)
• The I-PRESERVE trial randomised 4128 patients to irbesartan 300 mg or placebo for a mean 49.5 months and found no difference in death or cardiovascular hospitalisation (hazard ratio 0.95, 95% CI 0.86 to 1.05). Evidence: not-supported. (Source 5)
• ACTIVE I randomised 9016 patients with atrial fibrillation and found no reduction in the first coprimary outcome (5.4% per 100 person-years in both groups) and no benefit in preventing atrial fibrillation, with more symptomatic hypotension and renal dysfunction on irbesartan. Evidence: not-supported. (Source 6)
• The AIMS trial randomised 192 people aged 6 to 40 with Marfan syndrome and found aortic root dilatation of 0.53 mm per year on irbesartan versus 0.74 mm per year on placebo (difference -0.22 mm per year, p=0.030). This is a surrogate measurement of aortic size, not a trial of dissection, rupture or death. Evidence: limited. (Source 7)
• STOP-ACEi randomised 411 people with eGFR under 30 to stop or continue an ACE inhibitor or ARB. Stopping did not improve kidney function at three years and end-stage kidney disease was numerically more common in the stopping group (62% vs 56%). Evidence: disputed. (Source 8)

Interactions

• Potassium supplements and other agents that raise potassium (including potassium-sparing diuretics and potassium-containing supplements) (label): Adding anything that raises potassium to irbesartan can push potassium high enough to be dangerous. In the IDNT trial potassium above 6 mEq/L occurred in 18.6% on irbesartan versus 6.0% on placebo even without a supplement. (Source 9)
• Potassium-containing salt substitutes (25% potassium chloride) (clinical trial): Salt substitutes are a potassium load from food. In a 20,995-person cluster-randomised trial in people with stroke or hypertension, a 25% potassium chloride salt substitute reduced stroke and death and did not significantly increase serious hyperkalaemia; that trial was not restricted to people on renin-angiotensin blockers and did not report results separately for them, so it does not settle the risk for someone on irbesartan with reduced kidney function. (Source 10)
• NSAIDs including ibuprofen, naproxen and COX-2 inhibitors (label): Taken together with irbesartan in older, dehydrated or kidney-impaired people, NSAIDs can tip kidney function into acute failure, and they also blunt the blood-pressure-lowering effect. (Source 11)
• Lithium (label): Irbesartan can raise lithium blood levels, with reported lithium toxicity. (Source 9)
• ACE inhibitors and aliskiren (dual renin-angiotensin blockade) (clinical trial): Combining two renin-angiotensin blockers did not reduce death in a 68,405-patient meta-analysis but increased hyperkalaemia by 55%, hypotension by 66% and renal failure by 41%. (Source 12)
• Co-trimoxazole (sulfamethoxazole-trimethoprim) (case reports): The trimethoprim component blocks potassium excretion. In older people on an ACE inhibitor or ARB, a co-trimoxazole course was associated with roughly seven times the odds of being admitted to hospital with hyperkalaemia compared with amoxicillin. (Source 13)
• Food in general (label): Absorption is not meaningfully affected by food; the label allows it with or without food. (Source 14)

Stopping it

• Blood pressure does not rebound above baseline when irbesartan stops; the label reports about two thirds of the effect still present a week after the last dose of an 8-week course, with no rebound hypertension seen. (Source 15)
• In advanced chronic kidney disease, a randomised discontinuation trial found no kidney benefit from stopping a renin-angiotensin blocker, and end-stage kidney disease was numerically more frequent in those who stopped. (Source 8)
• The one circumstance where the label demands immediate stopping is pregnancy, because of the boxed fetal toxicity warning. (Source 2)
• Stopping or withholding is also advised when kidney function falls significantly on treatment. (Source 16)

What goes wrong

In the ACTIVE I trial irbesartan caused roughly twice as much symptomatic hypotension and renal dysfunction as placebo. (Source 6)

• Randomized trial, High certainty.
• Size: 9016 patients.
• Who: Adults with atrial fibrillation.
• How long: Mean 4.1 years.
• Result: Symptomatic hypotension 127 versus 64 patients; renal dysfunction 43 versus 24 patients.
• Funding: Industry-funded (Bristol-Myers Squibb and Sanofi-Aventis)

More patients in the irbesartan group than in the placebo group had symptomatic hypotension (127 vs. 64) and renal dysfunction (43 vs. 24).

In IDNT, the trial of people with type 2 diabetes and protein in the urine, serious hyperkalaemia was about three times as common on irbesartan as on placebo. (Source 17)

• Official position, Moderate certainty.
• Size: 1715 patients in IDNT.
• Who: Adults with type 2 diabetes, proteinuria of at least 900 mg/day and serum creatinine 1.0 to 3.0 mg/dL (IDNT)
• How long: Mean 2.6 years.
• Result: Potassium above 6 mEq/L in 18.6% on irbesartan versus 6.0% on placebo (absolute excess 12.6 percentage points, about 8 people treated per extra case); discontinuation for hyperkalaemia 2.1% versus 0.4%.
• Funding: FDA-approved labelling reporting trial data (label version effective 2026-08-24)

Limit of this finding: These potassium figures come from IDNT, a trial in people with type 2 diabetes and kidney disease, not from the trials in ordinary high blood pressure. The 18.6% rate should not be read as the rate for someone taking irbesartan for blood pressure alone; the label reports the two populations in separate sections.

the percent of patients with potassium >6 mEq/L was 18.6% in the AVAPRO group versus 6.0% in the placebo group

Dizziness and orthostatic symptoms were more frequent on irbesartan than placebo in IDNT, the diabetic nephropathy trial. (Source 17)

• Official position, Moderate certainty.
• Size: 1715 patients in IDNT.
• Who: Adults with type 2 diabetes and nephropathy (IDNT)
• How long: Mean 2.6 years.
• Result: Dizziness 10.2% versus 6.0%; orthostatic dizziness 5.4% versus 2.7%; orthostatic hypotension 5.4% versus 3.2%.
• Funding: FDA-approved labelling reporting trial data.

Limit of this finding: These rates are from the diabetic nephropathy population, not from the hypertension trials. The label states that apart from these orthostatic symptoms the reactions in IDNT were similar to those seen in people treated for hypertension.

an increased incidence of orthostatic symptoms which occurred more frequently in the AVAPRO versus placebo group: dizziness (10.2% vs 6.0%), orthostatic dizziness (5.4% vs 2.7%) and orthostatic hypotension (5.4% vs 3.2%)

In placebo-controlled hypertension trials the drug-versus-placebo excess of common side effects was small. (Source 18)

• Official position, Moderate certainty.
• Size: 1965 irbesartan and 641 placebo patients in placebo-controlled trials.
• Who: Adults with hypertension.
• How long: 8 to 12 weeks mostly.
• Result: Diarrhoea 3% versus 2%, dyspepsia or heartburn 2% versus 1%, fatigue 4% versus 3%.
• Funding: FDA-approved labelling reporting trial data.

diarrhea (3% vs 2%), dyspepsia/heartburn (2% vs 1%), and fatigue (4% vs 3%)

Combining an ARB with an ACE inhibitor or aliskiren did not reduce death but sharply increased hyperkalaemia, hypotension and renal failure. (Source 12)

• Meta-analysis, High certainty.
• Size: 68,405 patients across 33 randomised trials.
• Who: Adults with and without heart failure, mean age 61.
• How long: Mean 52 weeks.
• Result: All-cause mortality relative risk 0.97 (95% CI 0.89-1.06); hyperkalaemia +55% (P<0.001), hypotension +66% (P<0.001), renal failure +41% (P=0.01), withdrawal for adverse events +27% (P<0.001)
• Funding: Not stated in the abstract read.

dual therapy was associated with a 55% increase in the risk of hyperkalaemia (P<0.001), a 66% increase in the risk of hypotension (P<0.001), a 41% increase in the risk of renal failure (P=0.01)

One 2010 meta-analysis reported a small excess of new cancer diagnoses in ARB trials, a signal dominated by telmisartan rather than irbesartan. (Source 19)

• Meta-analysis, Low certainty.
• Size: 61,590 patients with new-cancer data across five trials.
• Who: Adults in long-term ARB trials; telmisartan accounted for 85.7% of ARB exposure.
• How long: At least one year.
• Result: New cancer 7.2% versus 6.0% (risk ratio 1.08, 95% CI 1.01-1.15, p=0.016); lung cancer 0.9% versus 0.7% (RR 1.25, 1.05-1.49, p=0.01); cancer deaths not significantly different (RR 1.07, 0.97-1.18)
• Funding: Not stated in the abstract read.

Limit of this finding: Almost all of the drug exposure in this analysis (85.7%) was telmisartan, not irbesartan, so it is weak evidence about irbesartan specifically. The larger pooled analysis of 15 trials, which included three irbesartan trials, found no excess cancer at all. This finding should not stand alone as the state of the evidence.

Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%, risk ratio [RR] 1.08, 95% CI 1.01-1.15; p=0.016)

Acute kidney injury and symptomatic low blood pressure are recognised harms of blocking the renin-angiotensin system, especially in people who are volume depleted or have renal artery narrowing. (Source 16)

• Official position, Moderate certainty.
• Size: Not applicable (regulatory warning)
• Who: Adults taking irbesartan, particularly those on high-dose diuretics or with renal artery stenosis, chronic kidney disease or severe heart failure.
• How long: Ongoing use.
• Result: No rate given; the label directs periodic monitoring of renal function and withholding the drug if function falls significantly.
• Funding: FDA-approved labelling (position of the regulator, 2026-08-24)

Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system.

What the evidence supports

In hypertensive people with type 2 diabetes and overt nephropathy, irbesartan 300 mg daily reduced a composite of doubled serum creatinine, end-stage kidney disease or death compared with placebo. (Source 4)

• Randomized trial, High certainty.
• Size: 1715 patients (579 irbesartan, 569 placebo, 567 amlodipine)
• Who: Hypertensive adults with type 2 diabetes, proteinuria of at least 900 mg/day and serum creatinine 1.0-3.0 mg/dL.
• How long: Mean 2.6 years.
• Result: Risk of the primary composite endpoint 20% lower than placebo (P=0.02) and 23% lower than amlodipine (P=0.006); doubling of creatinine 33% lower than placebo (P=0.003)
• Funding: Industry-funded (Bristol-Myers Squibb / Sanofi; Collaborative Study Group)

Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group (P=0.02) and 23 percent lower than that in the amlodipine group (P=0.006).

The label's own Table 1 puts the absolute size of the IDNT kidney benefit at about 6 percentage points over 2.6 years, which is roughly 16 people treated for one composite event avoided. (Source 20)

• Official position, Moderate certainty.
• Size: 1715 patients.
• Who: Hypertensive adults with type 2 diabetes and nephropathy.
• How long: Mean 2.6 years.
• Result: Table 1 of this label records the primary composite endpoint in 32.6% of 579 irbesartan patients versus 39.0% of 569 placebo patients (hazard ratio 0.80, 95% CI 0.66-0.97, p=0.0234): an absolute risk reduction of 6.4 percentage points, number needed to treat about 16.
• Funding: FDA-approved labelling (position of the regulator, label version effective 2026-08-24)

Limit of this finding: The quoted sentence gives only the relative figure, a 20% risk reduction. The absolute rates behind the 6 percentage points and the number needed to treat are read off Table 1 in the same label section, which the quoted sentence points to; they are not stated in the quote itself.

Treatment with AVAPRO resulted in a 20% risk reduction versus placebo (p=0.0234) (see Figure 3 and Table 1).

In hypertensive people with type 2 diabetes and microalbuminuria, irbesartan 300 mg daily reduced progression to overt diabetic nephropathy over two years. (Source 21)

• Randomized trial, Moderate certainty.
• Size: 590 patients (194 on 300 mg, 195 on 150 mg, 201 placebo)
• Who: Hypertensive adults with type 2 diabetes and microalbuminuria.
• How long: Two years.
• Result: 5.2% on 300 mg and 9.7% on 150 mg reached the endpoint versus 14.9% on placebo; hazard ratio 0.30 (95% CI 0.14-0.61, P<0.001) for 300 mg and 0.61 (95% CI 0.34-1.08, P=0.081) for 150 mg. Absolute risk reduction for 300 mg 9.7 percentage points, number needed to treat about 10.
• Funding: Industry-funded (Bristol-Myers Squibb / Sanofi; IRMA-2 investigators)

Ten of the 194 patients in the 300-mg group (5.2 percent) and 19 of the 195 patients in the 150-mg group (9.7 percent) reached the primary end point, as compared with 30 of the 201 patients in the placebo group (14.9 percent)

ARB monotherapy reduced end-stage kidney disease compared with placebo in a network meta-analysis of diabetic kidney disease trials. (Source 22)

• Meta-analysis, Moderate certainty.
• Size: 43,256 participants across 157 trials.
• Who: Adults with diabetes and chronic kidney disease.
• How long: Varied by trial.
• Result: End-stage renal disease odds ratio 0.77 (95% CI 0.65-0.92) for ARB monotherapy versus placebo.
• Funding: Canterbury Medical Research Foundation and the Italian Medicines Agency.

end-stage renal disease was significantly less likely after dual treatment with an angiotensin-receptor blocker (ARB) and an angiotensin-converting-enzyme (ACE) inhibitor (odds ratio 0·62, 95% CI 0·43-0·90) and after ARB monotherapy (0·77, 0·65-0·92)

As a class, ARBs lower trough blood pressure by about 8/5 mmHg at maximum recommended doses on the review's best estimate, and no one ARB is better than another. (Source 3)

• Systematic review, Moderate certainty.
• Size: 13,451 participants across 46 randomised trials.
• Who: Adults with primary hypertension, baseline blood pressure 156/101 mmHg.
• How long: 3 to 12 weeks.
• Result: Best estimate from the largest trials -8 mmHg systolic and -5 mmHg diastolic; 60 to 70% of that effect already achieved at one eighth to one quarter of the maximum dose.
• Funding: Cochrane Hypertension Group (independent)

Limit of this finding: The 8/5 mmHg figure is the review's estimate from its largest trials only, chosen because the smaller trials showed publication bias. It is not the average across all 46 trials, and the review does not give an irbesartan-specific figure.

the largest trials provide the best estimate of the trough BP lowering efficacy for ARBs as a class of drugs: -8 mm Hg for SBP and -5 mm Hg for DBP

Lowering systolic blood pressure by 10 mmHg, by whatever drug, was associated with about a fifth fewer major cardiovascular events and 13% lower all-cause mortality. (Source 23)

• Meta-analysis, High certainty.
• Size: 613,815 participants across 123 studies.
• Who: Adults in blood-pressure-lowering trials across a range of baseline pressures and comorbidities.
• How long: At least 1000 patient-years per arm.
• Result: Per 10 mmHg systolic reduction: major cardiovascular events RR 0.80 (95% CI 0.77-0.83), stroke 0.73 (0.68-0.77), heart failure 0.72 (0.67-0.78), all-cause mortality 0.87 (0.84-0.91); renal failure not significant at 0.95 (0.84-1.07)
• Funding: National Institute for Health Research and the Oxford Martin School (independent)

Every 10 mm Hg reduction in systolic blood pressure significantly reduced the risk of major cardiovascular disease events (relative risk [RR] 0·80, 95% CI 0·77-0·83)

In Marfan syndrome, irbesartan slowed the rate at which the aortic root widened, a surrogate measure rather than a clinical event. (Source 7)

• Randomized trial, Moderate certainty.
• Size: 192 participants (104 irbesartan, 88 placebo)
• Who: People aged 6 to 40 with clinically confirmed Marfan syndrome; 56% also on beta blockers.
• How long: Up to 5 years.
• Result: Aortic root dilatation 0.53 mm per year (95% CI 0.39-0.67) versus 0.74 mm per year (0.60-0.89); difference -0.22 mm per year (-0.41 to -0.02, p=0.030)
• Funding: British Heart Foundation, UK Marfan Trust, UK Marfan Association (not industry)

The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group

In placebo-controlled hypertension trials irbesartan did not cause the dry cough associated with ACE inhibitors: cough rates matched placebo. (Source 18)

• Official position, Moderate certainty.
• Size: Placebo-controlled hypertension trials.
• Who: Adults with hypertension.
• How long: 8 to 12 weeks mostly.
• Result: Cough 2.8% on irbesartan versus 2.7% on placebo.
• Funding: FDA-approved labelling reporting trial data.

the incidence of cough in irbesartan-treated patients was 2.8% versus 2.7% in patients receiving placebo

What the evidence does not support

IDNT found no reduction in death from any cause and no reduction in cardiovascular events with irbesartan. (Source 4)

• Randomized trial, High certainty.
• Size: 1715 patients.
• Who: Hypertensive adults with type 2 diabetes and nephropathy.
• How long: Mean 2.6 years.
• Result: No significant difference in all-cause mortality or in the secondary cardiovascular composite endpoint.
• Funding: Industry-funded (Bristol-Myers Squibb / Sanofi)

There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point.

In heart failure with a preserved ejection fraction, irbesartan did not reduce death or cardiovascular hospitalisation. (Source 5)

• Randomized trial, High certainty.
• Size: 4128 patients.
• Who: Adults at least 60 years old with NYHA class II-IV heart failure and ejection fraction of at least 45%.
• How long: Mean 49.5 months.
• Result: Primary event rate 100.4 versus 105.4 per 1000 patient-years (hazard ratio 0.95, 95% CI 0.86-1.05, P=0.35); death 52.6 versus 52.3 per 1000 patient-years (hazard ratio 1.00, 95% CI 0.88-1.14, P=0.98)
• Funding: Industry-funded (Bristol-Myers Squibb and Sanofi)

Primary event rates in the irbesartan and placebo groups were 100.4 and 105.4 per 1000 patient-years, respectively (hazard ratio, 0.95; 95% confidence interval [CI], 0.86 to 1.05; P=0.35).

In atrial fibrillation, irbesartan did not reduce stroke, myocardial infarction or vascular death despite lowering blood pressure. (Source 6)

• Randomized trial, High certainty.
• Size: 9016 patients.
• Who: Adults with atrial fibrillation, stroke risk factors and systolic blood pressure of at least 110 mmHg.
• How long: Mean 4.1 years.
• Result: First coprimary outcome 5.4% per 100 person-years in both arms (hazard ratio 0.99, 95% CI 0.91-1.08, P=0.85), despite a 2.9 mmHg greater systolic reduction.
• Funding: Industry-funded (Bristol-Myers Squibb and Sanofi-Aventis)

Limit of this finding: The trial reports its event rate as '5.4% per 100 person-years', which mixes up a percentage with a rate per 100 person-years. That is how the published abstract words it. The usable point is that the rate was the same in both groups.

The first coprimary outcome occurred at a rate of 5.4% per 100 person-years in both groups (hazard ratio with irbesartan, 0.99; 95% confidence interval [CI], 0.91 to 1.08; P=0.85).

A larger pooled analysis of 15 ARB trials, including three irbesartan trials, found no excess cancer. (Source 24)

• Meta-analysis, Moderate certainty.
• Size: 138,769 participants across 15 trials, including 14,859 in three irbesartan trials.
• Who: Adults at high cardiovascular risk.
• How long: 23 to 60 months.
• Result: Cancer in 4549 of 73,808 (6.16%) on ARB versus 3856 of 61,106 (6.31%) on control; odds ratio 1.00 (95% CI 0.95-1.04); no excess of lung, prostate or breast cancer.
• Funding: Not stated in the abstract read.

Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials

Stopping an ACE inhibitor or ARB in advanced chronic kidney disease did not improve kidney function at three years. (Source 8)

• Randomized trial, Moderate certainty.
• Size: 411 patients.
• Who: Adults with eGFR below 30 mL/min/1.73 m2 and progressive chronic kidney disease.
• How long: 3 years.
• Result: eGFR 12.6 mL/min/1.73 m2 after stopping versus 13.3 after continuing (difference -0.7, 95% CI -2.5 to 1.0, P=0.42); end-stage kidney disease or renal replacement in 62% versus 56% (hazard ratio 1.28, 95% CI 0.99-1.65)
• Funding: National Institute for Health Research and Medical Research Council (not industry)

ESKD or the initiation of renal-replacement therapy occurred in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (hazard ratio, 1.28; 95% CI, 0.99 to 1.65).

Where the evidence is mixed

Across 157 trials in diabetic kidney disease, no blood-pressure-lowering regimen including ARBs reduced death from any cause, although ARB monotherapy reduced end-stage kidney disease. (Source 22)

• Meta-analysis, Moderate certainty.
• Size: 43,256 participants across 157 trials.
• Who: Adults with diabetes and chronic kidney disease, mostly type 2.
• How long: Varied by trial.
• Result: No regimen beat placebo for all-cause mortality; end-stage renal disease odds ratio 0.77 (95% CI 0.65-0.92) for ARB monotherapy and 0.62 (0.43-0.90) for ARB plus ACE inhibitor.
• Funding: Canterbury Medical Research Foundation and the Italian Medicines Agency (not industry)

Limit of this finding: The quoted sentence also carries the figure for an ARB combined with an ACE inhibitor (odds ratio 0.62). The same analysis ranked that combination worst of all the options on harm, and the review does not recommend it. Read the 0.62 as part of a result that argues against dual blockade, not for it.

No drug regimen was more effective than placebo for reducing all-cause mortality.

The Cochrane review of ARBs says it could not estimate how often ARBs cause harm, because the trials were too short and many did not report adverse effects. (Source 25)

• Systematic review, Low certainty.
• Size: 46 randomised trials.
• Who: Adults with primary hypertension.
• How long: 3 to 12 weeks.
• Result: No usable harm estimate; the review names short duration and non-reporting as the reasons.
• Funding: Cochrane Hypertension Group (independent)

The review did not provide a good estimate of the incidence of harms associated with ARBs because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.

Where the research disagrees

Whether angiotensin receptor blockers increase the risk of new cancer

• Sipahi and colleagues (Lancet Oncology 2010 meta-analysis of five trials), meta-analysis of randomised controlled trials, dominated by telmisartan (85.7% of ARB exposure): Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%, risk ratio [RR] 1.08, 95% CI 1.01-1.15; p=0.016) (Source 19)
• ARB Trialists Collaboration (Journal of Hypertension 2011, 15 trials), larger pooled analysis of 15 randomised trials in 138,769 participants, including three irbesartan trials: Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials (Source 24)

Whether people with advanced chronic kidney disease should stop a renin-angiotensin blocker to preserve kidney function

• STOP-ACEi investigators (NEJM 2022), open-label randomised trial of discontinuation in 411 patients: ESKD or the initiation of renal-replacement therapy occurred in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (hazard ratio, 1.28; 95% CI, 0.99 to 1.65). (Source 8)
• Palmer and colleagues (Lancet 2015 network meta-analysis), network meta-analysis of 157 trials in diabetic kidney disease, which found kidney but not survival benefit: No drug regimen was more effective than placebo for reducing all-cause mortality. (Source 22)

How much

• Reference intake: There is no dietary reference intake for a prescription medicine. The dose is set by the prescriber. As a position, the FDA-approved label (version effective 2026-08-24) gives a starting dose of 150 mg once daily for hypertension, which may be increased to a maximum of 300 mg once daily (label section 2.2). Separate sections of the same label give 300 mg once daily for nephropathy in type 2 diabetic patients (section 2.3) and 75 mg once daily for people depleted of intravascular volume or salt (section 2.4). (Source 14)
• Upper limit: As a position, the same label (section 2.2) states the dose for hypertension can be increased to a maximum of 300 mg once daily, and the Cochrane review found doses above the maximum did not lower blood pressure further. (Source 14)
• Studied: IDNT gave irbesartan 300 mg daily (titrated from 75 mg) to 579 patients with diabetic nephropathy for a mean 2.6 years. (Source 26)
• Studied: IRMA-2 gave either 150 mg daily or 300 mg daily for two years in 590 patients with microalbuminuria. (Source 27)
• Studied: The AIMS Marfan trial started everyone on 75 mg once daily open label, then randomised to 150 mg increased to 300 mg as tolerated, or placebo. (Source 28)

A common belief, and what the research shows

The belief: A drug that protects the kidneys in diabetes must also help people live longer.

What the research shows: IDNT, the trial that established irbesartan's kidney benefit, found no survival benefit at all: "There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point." The Lancet network meta-analysis of 157 trials in diabetic kidney disease reached the same conclusion for the whole drug class: "No drug regimen was more effective than placebo for reducing all-cause mortality." The benefit is slower loss of kidney function, measured over years, not longer life.

Questions and answers

What is it?

Irbesartan is a prescription tablet in the angiotensin receptor blocker (ARB) family. It works by occupying the AT1 receptor so angiotensin II, the body's main blood-vessel-tightening hormone, cannot act there. It is highly selective, with more than 8500-fold greater affinity for AT1 than for the AT2 receptor. Unlike an ACE inhibitor it does not block angiotensin-converting enzyme. (Source 1)

What does it do in the body?

It blocks the vasoconstricting and aldosterone-releasing effects of angiotensin II. Blood vessels widen, the body retains less salt and water, and blood pressure falls by about 8/5 mmHg at maximum dose as a class. Pressure inside the kidney's filtering units also falls, which is thought to be why it slows protein leak and kidney scarring in diabetes. (Source 1)

Is it good or bad for you?

It depends entirely on who takes it. In hypertensive people with type 2 diabetes and kidney damage, IDNT showed a real benefit: the composite of doubled creatinine, kidney failure or death fell from 39.0% to 32.6% over 2.6 years. In heart failure with preserved ejection fraction and in atrial fibrillation it did nothing on hard outcomes. In pregnancy it is dangerous, and it carries a boxed warning for fetal injury and death. Hyperkalaemia is the main day-to-day risk. (Source 20)

How do you get more of it?

It is a prescription-only medicine, not a nutrient, so there is no food or supplement source and nothing a person should do to get more of it. Dose is set by a prescriber. The trials used 150 mg or 300 mg once daily; IDNT titrated from 75 mg to a maintenance dose of 300 mg daily. (Source 26)

If it is harmful, what reduces it?

If irbesartan is causing harm, it is stopped or withheld. Blood pressure does not rebound above baseline when it stops, and about two thirds of its effect is still present a week after the last dose, so the drug clears gradually. Stopping is required when pregnancy is detected and is advised when kidney function falls significantly. (Source 15)

Why might someone be low in it or missing it?

Someone may not be on irbesartan, or may be on a lower dose than the trials used, because of pregnancy (the boxed warning requires stopping), because potassium rose too high (2.1% of IDNT patients stopped for hyperkalaemia versus 0.4% on placebo), because kidney function fell, or because low blood pressure and dizziness made it intolerable. Only 83.0% of IDNT patients took the target 300 mg dose more than half the time. (Source 17)

Which whole foods contain it or feed it?

No whole food contains irbesartan. The food that matters is potassium: potassium-rich foods and especially potassium-chloride salt substitutes add to the potassium-raising effect of the drug. A 20,995-person randomised trial of a 25% potassium chloride salt substitute found fewer strokes and deaths and no significant excess of serious hyperkalaemia, but it did not report results separately for people on renin-angiotensin blockers. Irbesartan itself can be taken with or without food. (Source 10)

What happens if you do not have it?

The placebo arms of the trials answer this directly. Among hypertensive people with type 2 diabetes and overt nephropathy who got placebo, 39.0% reached doubled creatinine, end-stage kidney disease or death within a mean 2.6 years, compared with 32.6% on irbesartan. Among those with only microalbuminuria, 14.9% on placebo progressed to overt nephropathy in two years versus 5.2% on irbesartan 300 mg. Without any blood-pressure lowering at all, each 10 mmHg of systolic pressure left untreated carries about a fifth more major cardiovascular events. (Source 21)

How can you test for it?

There is no routine blood test for irbesartan itself in ordinary care. What is monitored is its effect: blood pressure, serum potassium and serum creatinine or eGFR. The label directs monitoring of renal function and serum potassium, and the IDNT data show why: 18.6% on irbesartan had potassium above 6 mEq/L versus 6.0% on placebo. These are well-standardised laboratory tests, though a single potassium can be falsely high if the blood sample haemolyses. (Source 17)

References

1. DailyMed / Sanofi-Aventis U.S. LLC (label version effective 2026-08-24). AVAPRO (irbesartan) tablet, film coated - FDA prescribing information, 12.1 Mechanism of Action. 2026. Read the source
2. DailyMed / Sanofi-Aventis U.S. LLC (label version effective 2026-08-24). AVAPRO (irbesartan) tablet, film coated - FDA prescribing information, BOXED WARNING: WARNING: FETAL TOXICITY (full prescribing information). 2026. Read the source
3. The Cochrane database of systematic reviews. Blood pressure lowering efficacy of angiotensin receptor blockers for primary hypertension. 2008. PMID 18843650, DOI 10.1002/14651858.cd003822.pub2. Read the source
4. The New England journal of medicine. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. 2001. PMID 11565517, DOI 10.1056/nejmoa011303. Read the source
5. The New England journal of medicine. Irbesartan in patients with heart failure and preserved ejection fraction. 2008. PMID 19001508, DOI 10.1056/nejmoa0805450. Read the source
6. The New England journal of medicine. Irbesartan in patients with atrial fibrillation. 2011. PMID 21388310, DOI 10.1056/nejmoa1008816. Read the source
7. Lancet (London, England). Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial. 2019. PMID 31836196, DOI 10.1016/s0140-6736(19)32518-8. Read the source
8. The New England journal of medicine. Renin-Angiotensin System Inhibition in Advanced Chronic Kidney Disease. 2022. PMID 36326117, DOI 10.1056/nejmoa2210639. Read the source
9. DailyMed / Sanofi-Aventis U.S. LLC (label version effective 2026-08-24). AVAPRO (irbesartan) tablet, film coated - FDA prescribing information, 7.1 Agents Increasing Serum Potassium and 7.2 Lithium. 2026. Read the source
10. The New England journal of medicine. Effect of Salt Substitution on Cardiovascular Events and Death. 2021. PMID 34459569, DOI 10.1056/nejmoa2105675. Read the source
11. DailyMed / Sanofi-Aventis U.S. LLC (label version effective 2026-08-24). AVAPRO (irbesartan) tablet, film coated - FDA prescribing information, 7.3 Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors). 2026. Read the source
12. BMJ (Clinical research ed.). Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials. 2013. PMID 23358488, DOI 10.1136/bmj.f360. Read the source
13. Archives of internal medicine. Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. 2010. PMID 20585070, DOI 10.1001/archinternmed.2010.142. Read the source
14. DailyMed / Sanofi-Aventis U.S. LLC (label version effective 2026-08-24). AVAPRO (irbesartan) tablet, film coated - FDA prescribing information, 2.1 General Considerations and 2.2 Hypertension. 2026. Read the source
15. DailyMed / Sanofi-Aventis U.S. LLC (label version effective 2026-08-24). AVAPRO (irbesartan) tablet, film coated - FDA prescribing information, 14.1 Hypertension. 2026. Read the source
16. DailyMed / Sanofi-Aventis U.S. LLC (label version effective 2026-08-24). AVAPRO (irbesartan) tablet, film coated - FDA prescribing information, 5.3 Impaired Renal Function. 2026. Read the source
17. DailyMed / Sanofi-Aventis U.S. LLC (label version effective 2026-08-24). AVAPRO (irbesartan) tablet, film coated - FDA prescribing information, 6.1 Clinical Trials Experience - Nephropathy in Type 2 Diabetic Patients. 2026. Read the source
18. DailyMed / Sanofi-Aventis U.S. LLC (label version effective 2026-08-24). AVAPRO (irbesartan) tablet, film coated - FDA prescribing information, 6.1 Clinical Trials Experience - Hypertension. 2026. Read the source
19. The Lancet. Oncology. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. 2010. PMID 20542468, DOI 10.1016/s1470-2045(10)70106-6. Read the source
20. DailyMed / Sanofi-Aventis U.S. LLC (label version effective 2026-08-24). AVAPRO (irbesartan) tablet, film coated - FDA prescribing information, 14.2 Nephropathy in Type 2 Diabetic Patients. 2026. Read the source
21. The New England journal of medicine. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. 2001. PMID 11565519, DOI 10.1056/nejmoa011489. Read the source
22. Lancet (London, England). Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. 2015. PMID 26009228, DOI 10.1016/s0140-6736(14)62459-4. Read the source
23. Lancet (London, England). Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. 2016. PMID 26724178, DOI 10.1016/s0140-6736(15)01225-8. Read the source
24. Journal of hypertension. Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals. 2011. PMID 21358417, DOI 10.1097/hjh.0b013e328344a7de. Read the source
25. The Cochrane database of systematic reviews. Blood pressure lowering efficacy of angiotensin receptor blockers for primary hypertension. 2008. PMID 18843650, DOI 10.1002/14651858.cd003822.pub2. Read the source
26. The New England journal of medicine. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. 2001. PMID 11565517, DOI 10.1056/nejmoa011303. Read the source
27. The New England journal of medicine. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. 2001. PMID 11565519, DOI 10.1056/nejmoa011489. Read the source
28. Lancet (London, England). Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial. 2019. PMID 31836196, DOI 10.1016/s0140-6736(19)32518-8. Read the source