Table 2—

Randomized controlled trials

StudyPopulation (age)*Definition of type 2 diabetesMean follow-up (years)/(rate)Incidence of type 2 diabetes RR (95% CI)Major limitations
ALLHAT (21)14,816 hypertensive patients from North America at high cardiovascular risk (≥55 years) (reserpine, clonidine and/or hydralazine were add-on therapy)FPG ≥7.0 mmol/l4 (38%)Amlodipine (9.8) vs. chlorthalidone (11.6%): 0.80 (0.64–0.99); lisinopril (8.1) vs. chlorthalidone (11.6%): rr 0.70 (0.56–0.86)1) Post hoc analysis; 2) of those that had a baseline FPG; measurement, only 38% had a repeat measurement at 4 years
ALPINE (22)392 hypertensive patients from Sweden (mean age 55 years)Physician-reported or prescription of diabetes medication or two FPG levels ≥7 mmol/l. Predefined end point1 (100%)Candesartan ± felodipine (0.5) vs. HCTZ ± atenolol (4.1%): 0.13 (0.02–0.99)1) Low number of type 2 diabetes case subjects (nine total) resulting in wide CIs
CAPPP (23)10,413 hypertensive patients from Sweden and Finland (25–66 years) (diuretics were second-line therapy in the ACE inhibitor arm and CCBs were add-on therapy in both arms)Two FPG levels ≥6.7 mmol/l (predefined end point)6.1 (100%)Captopril (6.5) vs. BB/thiazides (7.2%): 0.86 (0.74–0.99) from intention-to-treat analysis; 0.79 (0.67–0.94) from on-treatment analysis1) Open-label design; 2) add-on therapy in the ACE inhibitor group was a diuretic, which may have contaminated results; 3) relative proportions of patients on BB and thiazide therapy not given
CHARM (24)5,439 patients with symptomatic heart failure (≥18 years)Not specified (predefined end point)3.1 (100%)Candesartan (6) vs. placebo (7%): 0.78 (0.64–0.96)
EWPHE (25)840 patients enrolled in trial (≥60 years) (on-treatment analysis)Physician reported4.7 (85%)Triamterene plus HCTZ ± methyldopa (7.0) vs. placebo (4.7%): 1.5 (0.85–2.6)1) Post hoc analysis; 2) diagnosis depended on physician reporting; 3) small sample size
HAPPHY (26)6,569 caucasian men enrolled in the trial (40–64 years) (hydralazine and spironolactone were second-line agents)FPG >6.8 mmol/l and two positive urine dipsticks for glucosuria3.8 (98%)Thiazides (2.3) vs. BB (2.6%): 0.88 (0.65–1.19)1) Open-label design; 2) 4% of patients were on both thiazides and BB; 3) post hoc analysis
HOPE (27)5,720 patients from 19 countries at high cardiovascular risk (≥55 years)Patient self reported4.5 (99%)Ramipril (3.6) vs. placebo (5.4%): 0.66 (0.51–0.85)1) Diabetes not a predefined end point; 2) type 2 diabetes was self-reported
INSIGHT (28)5,019 hypertensive patients from Europe and Israel with at least one additional cardiovascular risk factor (55–80 years) (atenolol or enalapril were second-line agents)RPG >11.0 mmol/l or use of antidiabetic medication. Prespecified end point3 (98%)Nifedipine (4.3) vs. HCTZ/amiloride (5.6%): 0.77 (0.62–0.96)1) Relative percentage of patients on BBs and ACE inhibitors as second-line therapy in both study arms not stated
LIFE (29)7,998 hypertensive patients from the U.S. and Europe with left ventricular hypertrophy (55–80 years); (thiazides were the preferred second-line agent)2 FPG levels ≥6.7 mmol/l. Prespecified end point4.8 (99%)Losartan (6) vs. atenolol (8%): 0.75 (0.63–0.88)1) Results may represent a beneficial effect of losartan, a deleterious effect of atenolol, or both; 2) relative frequency of thiazide use in each study arm not given
NORDIL (30)10,154 hypertensive patients from Norway and Sweden (50–69 years) (ACE inhibitors or angiotension receptor blockers were add-on therapy in 25% of each study arm)Exact criteria not specified (predefined end point)4.5 (99%)Diltiazem (4) vs. diuretics/BB (5%): 0.87 (0.73–1.04)1) Open-label design (possible detection bias); 2) second-line agents were drugs from other study arms (contamination)
SCOPE (31)4,342 hypertensive patients with mild to moderate hypertension (70–89 years) (thiazides/BB were common second-line agents)Not specified (predefined end points)3.7 (100%)Candesartan (4.3) vs. placebo (5.3%): 0.81 (0.62–1.06)1) 84% of patients in the placebo group and 75% of patients in the candesartan group were on additional agents
SHEP (33)4,153 subjects from the U.S. with isolated systolic hypertension (≥60 years) (reserpine was an additional second-line agent)Self-reported or FPG ≥7.8 mmol/l or on antidiabetic medication3 (not reported)Chorthalidone ± atenolol (8.6) vs. placebo (7.5%): 1.2 (0.9–1.5)1) 33% of participants in the placebo arm were on active antihypertensive therapy at the end of the study; 2) post hoc analysis
STOP-2 (32)5,893 hypertensive patients from Sweden (70–84 years)Two FPG levels ≥6.7 mmol/l (predefined end points)4 (100%)ACE inhibitors vs. diuretics/BB: 0.96 (0.72–1.27); CCB vs. diuretics/BB: 0.97 (0.73–1.29); ACE inhibitors vs. CCB: 0.96 (0.74–1.31)§1) Open-label design; 2) second-line agents were drugs from other study arms (contamination)
Vermes et al (34)311 patients with left ventricular dysfunction from Canada (<80 years) (local center of SOLVD trial)FPG ≥7 mmol/l on two occasions2.9 (94%)Enalapril (6) vs. placebo (22%): 0.26 (0.13–0.53)1) Post hoc analysis of a single study center; 2) small sample size
  • *

    * Patients with diabetes at baseline are not included in the sample sizes reported.

  • Refers to the percentage of patients with complete follow-up.

  • RRs and CIs calculated from the data presented or obtained from study authors.

  • §

    § Incidence rates of type 2 diabetes not provided in STOP-2. BB, β-blockers; CCB, calcium channel blockers.