Effects of azilsartan compared with telmisartan on insulin resistance in patients with essential hypertension and type 2 diabetes mellitus: An open-label, randomized clinical trial

• Published in: PloS one 2019-04, Vol.14 (4), p.e0214727-e0214727
• Main Authors: Naruse, Mitsuhide, Koike, Yasuhiro, Kamei, Nozomu, Sakamoto, Ryuichi, Yambe, Yuko, Arimitsu, Michinori
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Analysis; Angiotensin; Angiotensin II; Angiotensins; Antihypertensive agents; Antihypertensives; Azilsartan medoxomil; Benzimidazoles - adverse effects; Benzimidazoles - therapeutic use; Biology and Life Sciences; Blood glucose; Blood pressure; Blood Pressure - drug effects; Clinical trials; Comparative analysis; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Dosage and administration; Drug therapy; Endocrinology; Fasting; Female; Glucose; Glycosylated hemoglobin; Homeostasis; Hospitals; Humans; Hypertension; Hypertension - complications; Hypertension - drug therapy; Insulin; Insulin Resistance; Male; Medicine and Health Sciences; Metabolism; Middle Aged; Oxadiazoles - adverse effects; Oxadiazoles - therapeutic use; Patients; Studies; Telmisartan; Telmisartan - adverse effects; Telmisartan - therapeutic use; Tumor necrosis factor-TNF; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0214727

Based on non-clinical data, it is expected that azilsartan, an angiotensin II receptor blocker, will help improve insulin resistance in addition to its hypotensive action. The present study is aimed to explore the effect of azilsartan compared to telmisartan on insulin sensitivity in hypertensive patients in the clinical setting. This multicenter, randomized, open-label, parallel-group exploratory study was conducted in Japan. We randomized adult patients (≥20 years old) with grade I or II essential hypertension and coexisting type 2 diabetes (1:1) to receive either oral azilsartan (20 mg/day;17 patients) or telmisartan (40 mg/day;16 patients) for 12 weeks. The primary endpoint was the change in the homeostasis model assessment ratio of insulin resistance (HOMA-R) from the baseline at the end of the treatment period. We also evaluated its safety and efficacy on other diabetes-related variables and blood pressure. The mean changes in HOMA-R at the end of treatment were 0.22 (95% CI, -1.09-1.52) in the azilsartan group and -0.23 (95% CI, -0.72-0.27) in the telmisartan group. We found no clinically remarkable changes between the groups in diabetes-related variables such as fasting blood glucose, fasting insulin, HbA1c (NGSP), HOMA-β, or 1,5-anhydroglucitol. Reductions in clinic systolic and diastolic blood pressure were observed at week 4 and the reduced levels were maintained throughout the treatment period in both groups. No serious treatment-emergent adverse events (TEAEs) were observed. Only one drug-related TEAE (mild decrease in blood pressure) was reported in one patient in the azilsartan group. Neither azilsartan nor telmisartan had any clinically remarkable effects on insulin resistance parameters when administered for 12 weeks to patients with grade I or II essential hypertension and coexisting type 2 diabetes mellitus. Azilsartan (20 mg/day) and telmisartan (40 mg/day) exerted comparable antihypertensive effects. ClinicalTrials.gov NCT02079805.