Anti-inflammatory potential of telmisartan compared to other antihypertensives: secondary outcomes from a randomized trial

Abstract

Background: Chronic low-grade inflammation plays a central role in the pathophysiology of both type 2 diabetes mellitus (T2DM) and hypertension, contributing to increased cardiovascular risk. Telmisartan, an angiotensin receptor blocker with partial peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist activity, may offer anti-inflammatory benefits in addition to its antihypertensive effects.

Aims: This study compares the effects of telmisartan versus other standard antihypertensive agents on inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α), in patients with diabetes and newly diagnosed hypertension.

Methods: This is a randomized, open-label, parallel-group, active-controlled trial. Seventy eligible patients were randomized to receive telmisartan (N = 34) or another antihypertensive agent [amlodipine (n = 22), cilnidipine (n = 12), or ramipril (n = 2)] (N = 36). Secondary outcome parameters included inflammatory biomarkers such as highly sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumour necrosis factor alpha (TNF-α) measured at baseline and 12 weeks following treatment. Data are presented as median and interquartile range (IQR). Between-group comparisons at 12 weeks were performed using the Mann-Whitney U test. The trial is registered with the Clinical Trial Registry of India (CTRI/2023/04/051878).

Results: At baseline, hsCRP, IL-6, and TNF-α levels were comparable between groups. In the telmisartan group, hsCRP declined from 3.4 mg/L (IQR: 2.0, 13.7) to 1.8 mg/L (IQR: 1.2, 5.0), IL-6 from 4.3 pg/mL (IQR: 2.9,9.5) to 3.4 pg/ml (IQR: 2.2, 6.8), and TNF-α from 19.4 pg/ml (IQR: 8.9, 43.7) to 13.8 pg/ml (IQR: 3.5, 32.4). In the active control group, hsCRP changed from 3.1 mg/L (IQR: 1.7, 8.0) to 2.9 mg/L (IQR: 1.7, 4.9), IL-6 from 4.1 pg/ml (IQR: 3.0,7.6) to 4.2 pg/ml (IQR: 2.9, 7.8), and TNF-α from 20.2 pg/ml (IQR: 10.4, 48.6) to 16.9 pg/ml (IQR: 3.3, 30.3). The differences between groups at 12 weeks were not statistically significant for hsCRP (P = 0.07), IL-6 (P = 0.24), or TNF-α (P = 0.93).

Conclusion: The anti-inflammatory markers were reduced in both groups at 12 weeks without any statistically significant difference across groups. However, telmisartan was associated with greater reductions in hsCRP, IL-6, and TNF-α in patients with T2DM and hypertension following 12 weeks of treatment. These findings may indicate a potential anti-inflammatory effect of telmisartan that requires confirmation in adequately powered trials.

Keywords: High sensitivity C- reactive protein; Hypertension; Interleukin-6; Randomised trial; Tumour necrosis factor-alpha; Type 2 diabetes.