Ramipril-based versus diuretic-based antihypertensive primary treatment in patients with pre-diabetes (ADaPT) study

Previous randomized controlled trials demonstrated a protective effect of renin angiotensin system blocking agents for the development of type-2 diabetes in patients with pre-diabetes. However, there are no real-world data available to illustrate the relevance for clinical practice.

Open, prospective, parallel group study comparing patients with an ACE inhibitor versus a diuretic based treatment. The principal aim was to document the first manifestation of type-2 diabetes in either group.

A total of 2,011 patients were enrolled (mean age 69.1±10.3 years; 51.6% female). 1,507 patients were available for the per-protocol analysis (1,029 ramipril, 478 diuretic group). New-onset diabetes was less frequent in the ramipril than in the diuretic group over 4 years. Differences were statistically different at a median duration of 3 years (24.4% vs 29.5%; p<0.05). Both treatments were equally effective in reducing BP (14.7±18.0/8.5±8.2 mmHg and 12.7±18.1/7.0±8.3 mmHg) at the 4 year follow-up (p<0.001 vs. baseline; p=n.s. between groups). In 38.6% and 39.7% of patients BP was below 130/80 mmHg (median time-to-target 3 months). There was a significant reduction of cardiovascular morbidity and mortality in favour of ramipril (p=0.033). No significant differences were found for a change in HbA1c as well as for fasting blood glucose levels during follow-up. The rate of adverse events was higher in diuretic treated patients (SAE 15.4 vs. 12.4%; p<0.05; AE 26.6 vs. 25.6%; p=n.s).

Ramipril treatment is preferable over diuretic based treatment regimens for the treatment of hypertension in pre-diabetic patients, because new-onset diabetes is delayed.