Impact of telmisartan on metabolic and vascular outcomes in hypertensive patients with type 2 diabetes: A randomised open-label trial
Dr. Rimple Jeet Kaur PhD1, Simi Bridjit Gomaz MD1, Jaykaran Charan MD1, Deepak Kumar MD2, Dharmveer Yadav PhD3, Ravindra Shukla DM4, Sneha Ambwani MD1, Amal Mohandas MD3, 1Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur- 342005, Rajasthan, India 2Department of Gen. Medicine, All India Institute of Medical Sciences, Jodhpur- 342005, Rajasthan, India 3 Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur- 342005, Rajasthan, India 4Department of Endocrinology and metabolism, All India Institute of Medical Sciences, Jodhpur- 342005, Rajasthan, India

Introduction. Insulin resistance and elevated endothelin-1 (ET-1) levels are key contributors to cardiovascular and renal complications in patients with type 2 diabetes mellitus (T2DM) and hypertension. Telmisartan, an angiotensin receptor blocker with partial peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist activity, may offer metabolic advantages beyond blood pressure control. This study compared the effects of telmisartan with other commonly used antihypertensive agents on insulin sensitivity and ET-1 levels in patients with T2DM and hypertension.
Aims. This study evaluated the effects of telmisartan beyond its efficacy 
in blood pressure regulation, specifically its impact 

on insulin resistance and endothelial dysfunction                                       
in comparison to other commonly prescribed
 first line antihypertensive in patients of T2DM with hypertension 
Methods. In this randomized, open-label study, 182 patients 
with coexisting T2DM and newly diagnosed hypertension
were screened between May 2023 and September 2024. 
Seventy eligible patients were enrolled and randomized 1:1 to 
receive telmisartan (n=34) or other antihypertensive agents 
(amlodipine, n=22; cilnidipine, n=12; ramipril, n=2; total n=36) 
for 12 weeks. The primary outcome was the change in insulin 
sensitivity as measured by the homeostatic model assessment of 
insulin resistance (HOMA-IR). ET-1 levels, a marker of 
endothelial dysfunction and chronic kidney disease, 
were evaluated as a secondary outcome. 
Results. At baseline, the median HOMA-IR values were 4.1 (IQR: 2.2–5.9) in the telmisartan group (n=34) and 3.9 (IQR: 3.1–5.9) in the comparator group(n=36). After 12 weeks, the median HOMA-IR significantly decreased in the telmisartan group to 1.79 (IQR: 1.30–2.63) compared to 3.45 (IQR: 2.43–5.12) in the other antihypertensive group (P = 0.001). Baseline ET-1 levels were 19.23 pg/mL (IQR: 10.02–29.59) and 20.72 pg/mL (IQR: 5.68–28.11) in the telmisartan and comparator groups, respectively. At 12 weeks, median ET-1 levels decreased to 12.49 pg/mL (IQR:5.70–18.70) and11.22pg/mL (IQR:4.28, 23.20), respectively (P=0.90, between groups).
Discussion. The present study demonstrates a greater improvement in insulin resistance, as measured by HOMA-IR, in the telmisartan group compared to the other antihypertensive treatment group. This finding is consistent with previous research highlighting telmisartan's PPAR-γ agonistic activity. In addition to its antihypertensive effects, telmisartan appears to confer favourable metabolic benefits that may contribute to the attenuation of accelerated atherosclerosis and reduction in future cardiovascular risk. However, the reduction in endothelin-1 (ET-1) levels was comparable between groups, suggesting a similar effect on endothelial function over the 12-week treatment period. A longer study duration may be necessary to determine whether the insulin-sensitizing effects of telmisartan translate into differential changes in ET-1 levels over time.

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