Telmisartan or Losartan: What Is the Difference
Telmisartan and losartan belong to the same class — angiotensin II receptor blockers, or sartans. Both lower blood pressure and protect target organs, yet there are substantial differences between them in pharmacokinetics, duration of action and additional effects. The editorial team examines what exactly distinguishes these molecules.
A common foundation: how sartans work
The renin-angiotensin system is one of the main regulators of blood pressure and water-salt balance. Its key hormone, angiotensin II, constricts vessels, stimulates the production of aldosterone (which retains sodium and water), enhances sympathetic activity and promotes remodeling of the heart and vessels.
Sartans block type 1 angiotensin II receptors (AT1). The hormone continues to be produced but cannot transmit its signal. As a result, vessels dilate, sodium retention decreases and blood pressure falls. Unlike ACE inhibitors, sartans do not affect the breakdown of bradykinin, so they rarely cause a dry cough.
Losartan became the first sartan on the market in the mid-1990s and effectively opened up an entire class. Telmisartan appeared later and belongs to the molecules with the longest half-life among sartans.
Both drugs are among the main classes of antihypertensive agents according to the European hypertension guidelines (ESC/ESH 2018, ESH 2023). So the question is not whether they work, but exactly how they differ.
Pharmacokinetics: the main difference
Losartan is partly a prodrug. After absorption, a significant part of it is converted in the liver, with the participation of the enzymes CYP2C9 and CYP3A4, into the active metabolite EXP3174, which blocks AT1 receptors much more strongly than the parent molecule. The half-life of losartan itself is about two hours, and of the metabolite — approximately 6–9 hours.
Telmisartan acts directly, without requiring activation. It is highly lipophilic, penetrates tissues well and has the longest half-life among sartans — about a day. It is eliminated predominantly with bile rather than by the kidneys.
The practical consequence is a different “evenness” of action over the course of the day. Telmisartan provides a more stable reduction in blood pressure in the final hours before the next dose, particularly in the morning hours, when the risk of cardiovascular events is highest. Some patients may need to take losartan twice a day for full 24-hour control.
| Parameter | Losartan | Telmisartan |
|---|---|---|
| Activation | Partly via the metabolite EXP3174 | Active in the original form |
| Half-life | ~2 h (metabolite ~6–9 h) | ~24 h |
| Metabolism | CYP2C9, CYP3A4 | Glucuronidation, without significant CYP involvement |
| Main route of elimination | Bile and kidneys | Predominantly bile |
| Dose range per labeling | 25–100 mg/day | 20–80 mg/day |
The absence of significant involvement of the cytochrome P450 system in the metabolism of telmisartan means fewer potential drug interactions. At the same time, because of its elimination with bile, it requires caution in severe liver diseases and biliary tract obstruction.
Additional properties of each molecule
Telmisartan was found to have the ability to partially activate PPAR-gamma receptors — the same ones acted on by some antidiabetic drugs. Laboratory studies (Benson et al., 2004) demonstrated this property in cell models. Hence the interest in a possible beneficial effect on insulin sensitivity and lipid metabolism.
However, it is important not to overestimate this effect: clinical data on the metabolic benefits of telmisartan are inconsistent, and the strength of its PPAR-gamma activity at therapeutic doses is insufficient to consider it an antidiabetic agent.
Losartan has its own unique feature — a uricosuric action. It increases the excretion of uric acid by the kidneys and moderately lowers its level in the blood. For people with hyperuricemia or gout this can be an advantage, all the more so because thiazide diuretics, which are often combined with sartans, on the contrary raise uric acid levels.
Other sartans, including telmisartan, do not have such a clinically significant effect on uric acid. This is one of the few differences within the class that genuinely affects the choice.
The evidence base of large studies
Losartan has been studied in several landmark trials. In LIFE (Dahlöf et al., 2002), in patients with hypertension and left ventricular hypertrophy, losartan-based therapy reduced the rate of cardiovascular events, primarily strokes, better than atenolol-based therapy. In RENAAL (Brenner et al., 2001), losartan slowed the progression of diabetic nephropathy in type 2 diabetes.
Telmisartan was studied in the ONTARGET/TRANSCEND program. In ONTARGET (2008) it proved no worse than ramipril for cardiovascular events in high-risk patients, but the combination of the two drugs did not provide an advantage and increased the rate of side effects, in particular worsening of kidney function. On the basis of these data, telmisartan received an indication for reducing cardiovascular risk.
These studies had different populations and different comparisons, so their results cannot be directly compared. There are no large randomized “telmisartan versus losartan” trials with hard endpoints.
The conclusion of ONTARGET has practical significance: dual blockade of the renin-angiotensin system (a sartan together with an ACE inhibitor) is not recommended in general practice.
Tolerability and limitations
Overall, sartans are among the best-tolerated antihypertensive drugs. The side effects of both molecules are similar:
- dizziness, especially at the start of treatment or with dehydration;
- increased blood potassium levels, especially in kidney diseases, when taking potassium-sparing diuretics or potassium supplements;
- a temporary rise in creatinine after the start of therapy;
- rarely — angioedema, although much less often than with ACE inhibitors.
Both drugs are contraindicated during pregnancy, since drugs acting on the renin-angiotensin system can damage the kidneys and other organs of the fetus. For women planning pregnancy, a doctor selects a different therapy.
A dangerous combination is a sartan, a diuretic and nonsteroidal anti-inflammatory drugs — the so-called “triple whammy” to the kidneys. For physically active people who regularly take painkillers after workouts, this is a real risk.
Neither of these drugs is on the WADA Prohibited List, but the diuretics with which they are often combined in fixed-dose tablets are prohibited as masking agents. Athletes should carefully read the composition of combined drugs.
Editorial conclusions
Telmisartan and losartan share a mechanism but have different pharmacokinetics: telmisartan acts longer and more evenly, while losartan depends on the active metabolite and has a shorter action.
The unique feature of losartan is a moderate reduction in uric acid; of telmisartan — partial PPAR-gamma activity, the clinical significance of which is limited.
Both drugs have a solid evidence base, but in different populations. The choice between them depends on comorbid conditions, not on one being “stronger.”
We examine the practical side of the choice in the article “Telmisartan vs Losartan: What to Choose and for Whom.” We also recommend materials on blood pressure control in strength sports and on tests for potassium and creatinine.
References
- Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):995–1003.
- Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–869.
- ONTARGET Investigators; Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–1559.
- Benson SC, Pershadsingh HA, Ho CI, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARgamma-modulating activity. Hypertension. 2004;43(5):993–1002.
- Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021–3104.
- Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension. J Hypertens. 2023;41(12):1874–2071.
- World Anti-Doping Agency. The Prohibited List. Montreal: WADA; щорічне видання.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
