Rationale for use of the fixed combination of delapril and manidipine in the treatment of hypertension in patients with diabetes mellitus

Background: The fixed combination of the angiotensin-converting enzyme (ACE) inhibitor delapril and the dihydropyridine calcium channel blocker manidipine is a new oral, QD antihypertensive regimen that may have a role in the management of hypertension in patients with diabetes mellitus (DM). Objective: The purpose of this article was to briefly review the evidence regarding the efficacy, tolerability, and potential clinical benefits of delapril and manidipine (as single agents and in combination) in hypertensive patients with type 2 DM. Methods: A MEDLINE search (1992-2006) was performed using delapril and manidipine as search terms to identify key studies on the pharmacokinetics, efficacy, and tolerability of these agents in hypertensive patients with DM. Additional nonindexed studies and meeting abstracts were identified by examining the reference citations from the studies in the MEDLINE output. Results: Delapril/manidipine offers several potential benefits in hypertensive patients with type 2 DM. In clinical trials, the combination was as effective as ramipril/hydrochlorothiazide (HCTZ), valsartan/HCTZ, olmesartan/HCTZ, and irbesartan/HCTZ. Delapril/manidipine is associated with a low incidence of ankle edema and does not appear to have an orthostatic hypotensive effect. The combination has renoprotective benefits, reducing microalbuminuria and stabilizing serum creatinine levels. Delapril/manidipine does not appear to affect glucose metabolism or glycemic control. In addition, there is evidence that the combination increases insulin sensitivity, improves coagulation (via an increase in tissue plasminogen activity), and reduces left ventricular mass in diabetic hypertensive patients. Conclusion: The properties of delapril and manidipine make this ACE inhibitor/calcium channel block- er combination a valuable treatment option for hypertension in patients with type 2 DM, a population that is particularly difficult to treat.