Angiotensin II receptor blockers decreased blood glucose levels: a longitudinal survey using data from electronic medical records

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A beneficial effect on glucose metabolism is reported with angiotensin receptor blocker (ARB) treatment of hypertension. The effect on blood glucose level during the course of treatment with ARBs in clinical cases is uncertain. Our objectives were to survey the changes in glucose and HbA1c levels in patients with hypertension over a one-year period, and to study the correlations between these values and the time after the start of ARB therapy.

We conducted a retrospective longitudinal survey of blood glucose and HbA1c measurements in Japanese patients aged ≥20 years with newly diagnosed hypertension but without diabetes, who had received ARB monotherapy with candesartan cilexetil, losartan potassium, olmesartan medoxomil, telmisartan, or valsartan during the period from December 2004 to November 2005. Data including 2465 measurements of non-fasting blood glucose in 485 patients and 457 measurements of HbA1c in 155 patients were obtained from electronic medical records of Nihon University School of Medicine. Linear mixed effects models were used to analyze the relationship between these longitudinal data of blood examinations and covariates of patient age, sex, medication, and duration of ARB therapy.

Casual blood glucose level was associated with the duration of treatment (P < 0.0001), but not with age, sex, or medication. Blood glucose level was significantly decreased during the periods of 0~3 months (P < 0.0001) and 3~6 months (P = 0.0081) compared with baseline, but was not significantly different between 6~12 months and baseline. There was no association between HbA1c level and covariates of sex, age, medication and duration of treatment.

Our findings provide new clinical evidence that the effects of ARBs on glucose metabolism may change during the course of treatment, suggesting a blood glucose-lowering effect in the short-term after the start of treatment.


Clinically, there are many cases in which abnormal glucose metabolism and hypertension appear together. Knowing the effects of blood pressure-lowering agents on blood glucose is important for the treatment of hypertensive patients with abnormalities of glucose metabolism or diabetes. The agents most often used for hypertension today include angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors, which are both considered to improve glucose metabolism 1,2. In addition, much attention has been paid to a prospective clinical trial that showed that ACE inhibitors suppressed the new onset of diabetes 3. A subsequent report showed that ARBs also suppressed the new onset of diabetes 4. The magnitude of this effect was around 20–25%. Recent animal experiments have suggested improvement of insulin resistance by ARBs 5,6. Clarification of the mechanism of this effect is in progress.



  1. Folli F, Kahn CR, Hansen H, Bouchie JL, Feener EP: Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk. J Clin Invest 1997, 100(9):2158-2169.
  2. Folli F, Saad MJ, Velloso L, Hansen H, Carandente O, Feener EP, Kahn CR: Crosstalk between insulin and angiotensin II signalling systems. Exp Clin Endocrinol Diabetes 1999, 107(2):133-139.
  3. Fujimoto M, Masuzaki H, Tanaka T, Yasue S, Tomita T, Okazawa K, Fujikura J, Chusho H, Ebihara K, Hayashi T, et al.: An angiotensin II AT1 receptor antagonist, telmisartan augments glucose uptake and GLUT4 protein expression in 3T3-L1 adipocytes. FEBS Lett 2004, 576(3):492-497.
  4. Furuhashi M, Ura N, Higashiura K, Murakami H, Tanaka M, Moniwa N, Yoshida D, Shimamoto K: Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension. Hypertension 2003, 42(1):76-81.
  5. Haenni A, Lithell H: Treatment with a beta-blocker with beta 2-agonism improves glucose and lipid metabolism in essential hypertension. Metabolism 1994, 43(4):455-461.
  6. Kaplan NM: Effects of antihypertensive therapy on insulin resistance. Hypertension 1992, 19(1 Suppl):I116-118.
  7. Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, Nanjo K, Sasaki A, Seino Y, Ito C, et al.: Report of the Committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract 2002, 55(1):65-85.
  8. Fitzmaurice GM, Laird NM, Ware JH: Applied longitudinal analysis. New York: John Wiley & Sons, Inc; 2004.
  9. Landsberg L: Insulin sensitivity in the pathogenesis of hypertension and hypertensive complications. Clin Exp Hypertens 1996, 18(3├óÔé¼ÔÇ£4):337-346.
  10. Landsberg L: Insulin-mediated sympathetic stimulation: role in the pathogenesis of obesity-related hypertension (or, how insulin affects blood pressure, and why). J Hypertens 2001, 19(3 Pt 2):523-528.
  11. Lithell H, Pollare T, Vessby B: Metabolic effects of pindolol and propranolol in a double-blind cross-over study in hypertensive patients. Blood Press 1992, 1(2):92-101.
  12. Okada K, Hirano T, Ran J, Adachi M: Olmesartan medoxomil, an angiotensin II receptor blocker ameliorates insulin resistance and decreases triglyceride production in fructose-fed rats. Hypertens Res 2004, 27(4):293-299.
  13. Paolisso G, Gambardella A, Verza M, D'Amore A, Sgambato S, Varricchio M: ACE inhibition improves insulin-sensitivity in aged insulin-resistant hypertensive patients. J Hum Hypertens 1992, 6(3):175-179.
  14. Ran J, Hirano T, Fukui T, Saito K, Kageyama H, Okada K, Adachi M: Angiotensin II infusion decreases plasma adiponectin level via its type 1 receptor in rats: an implication for hypertension- related insulin resistance. Metabolism 2006, 55(4):478-488.
  15. Scheen AJ: Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms. Diabetes Metab 2004, 30(6):498-505.
  16. Scheen AJ: Prevention of type 2 diabetes mellitus through inhibition of the Renin-Angiotensin system. Drugs 2004, 64(22):2537-2565.
  17. Scheen AJ: Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials. Diabetes Metab 2004, 30(6):487-496.
  18. Schupp M, Clemenz M, Gineste R, Witt H, Janke J, Helleboid S, Hennuyer N, Ruiz P, Unger T, Staels B, et al.: Molecular characterization of new selective peroxisome proliferator-activated receptor gamma modulators with angiotensin receptor blocking activity. Diabetes 2005, 54(12):3442-3452.
  19. Weir MR, Dzau VJ: The renin-angiotensin-aldosterone system: a specific target for hypertension management. Am J Hypertens 1999, 12(12 Pt 3):205S-213S.