Background and objectives 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. This study compared the effects of telmisartan with other commonly used antihypertensive agents on insulin sensitivity in terms of homeostatic model assessment for insulin resistance (HOMA-IR) and vascular endothelial function in terms of ET-1 levels in patients with T2DM and hypertension. Methods In this randomised, open-label study, 182 patients with coexisting T2DM and hypertension were screened between May 2023 and September 2024. The study was registered with the Clinical Trials Registry-India (CTRI; CTRI/2023/04/051878). Seventy eligible patients were enrolled and randomised 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 HOMA-IR. ET-1 levels were evaluated as a secondary outcome. Results At baseline, the median HOMA-IR values were 4.1 [interquartile range (IQR): 2.2-5.9] in the telmisartan group and 3.9 (IQR: 3.1-5.9) in the comparator group. 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: 10.8-29.9) and 17.1 pg/mL (IQR: 10.3-26.48) 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) and 11.22 pg/mL (IQR:4.84-23.20), respectively (P=0.90). Interpretation and conclusions Telmisartan significantly improved insulin sensitivity at 12 weeks compared to other antihypertensive agents in patients with T2DM and hypertension. However, the reduction in ET-1 levels was similar across groups, suggesting a comparable effect on endothelial function over 12 weeks. These findings suggest that, beyond its antihypertensive action, telmisartan may offer favourable metabolic benefits that could help limit diabetes-related micro- and macrovascular complications compared with other commonly prescribed antihypertensives.