Losartan attenuates symptomatic and hormonal responses to hypoglycemia in humans

Objective: Reduced awareness of hypoglycemic symptoms and compromised hormo nal counterregulation increase the risk of severe hypoglycemia in people wi th diabetes mellitus. Up to the present, angiotensin 1 receptor blockers, w hich play an important role in controlling diabetic complications, have not been known to increase the risk of hypoglycemia. Nevertheless, we observed 3 cases of diabetic patients complaining of reduced awareness of hypoglyce mic symptoms while they were under treatment with losartan in our outpatien ts clinic. We therefore investigated the effects of losartan on symptomatic and hormonal responses to hypoglycemia in humans. Research design and methods: We carried out a randomized, double-blind, cro ssover study including 16 healthy men. The subjects received losartan 50 mg /d versus placebo. Treatment periods lasted for 7 days and were followed by a stepwise hypoglycemic clamp session (4.5 to 3.8 to 3.1 to 2.4 mmol/L) wi th measurement of counterregulatory hormones (epinephrine, norepinephrine, adrenocorticotropin, cortisol, glucagon), symptoms, and hemodynamic paramet ers (blood pressure, heart rate). Results: Losartan attenuated the hypoglycemia-induced rise in plasma epinep hrine (6480 +/- 490 pmol/L versus placebo 8970 +/- 790 pmol/L; P < .001) an d the rise in plasma adrenocorticotropin (21 +/- 2 pmol/L versus 26 +/- 3 p mol/L; P < .01). Losartan also reduced symptom scores during hypoglycemia ( P < .05). Conclusion: We conclude that short-term treatment with losartan slightly at tenuates symptomatic and hormonal responses to hypoglycemia. At present, fo r patients who are unaware of hypoglycemia and who require antihypertensive or nephroprotective treatment, we would recommend caution concerning treat ment with losartan.