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Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension.

Brown MJ, Williams B, MacDonald TM, Caulfield M, Cruickshank JK, McInnes G, Sever P, Webb DJ, Salsbury J, Morant S, Ford I - BMJ Open (2015)

Bottom Line: We hypothesised that a K(+)-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K(+)-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide.The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24.PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pharmacology Unit, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK Trial Executive for the British Hypertension Society's PATHWAY Programme of Trials Steering Committee for the British Hypertension Society's PATHWAY Programme of Trials.

No MeSH data available.


Related in: MedlinePlus

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Mentions: Diuretics and new-onset diabetes: A major attraction of K+-sparing diuretics is the possibility that they will offset the diabetogenic potential of thiazides. Since they have not been compared in hypertension outcome trials, and diabetes (DM) has not been an end point in heart failure studies of spironolactone or eplerenone, we do not know for certain whether they are clean in this respect. Short-term studies suggest they are.10 Interestingly in INSIGHT there was no excess of DM in patients receiving hydrochlorothiazide (HCTZ) 25 mg, which was combined with amiloride 2.5 mg, but increased by 30% in patients on HCTZ/amiloride 50/5 mg.6 In PATHWAY-3, we use the oral glucose tolerance test (OGTT) to provide an end point for each subject. This strategy was previously used to demonstrate a difference after just 12 weeks of dosing with a thiazide diuretic.11 In the STAR study, which compared 200 markedly obese patients randomly assigned to either ACE inhibitor +Ca++ blocker, or ARB+thiazide, the subjects had impaired glucose tolerance at entry, allowing detection of changes on low-dose thiazide. Subsequently, two small crossover studies in about 40 patients showed a rise in 2 h glucose within 4 weeks of treatment with bendroflumethiazide 5 mg or HCTZ 50 mg, with a highly significant difference from the 2 h glucose during 4 weeks of treatment with amiloride 20 mg (figures 1 and 2).12


Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension.

Brown MJ, Williams B, MacDonald TM, Caulfield M, Cruickshank JK, McInnes G, Sever P, Webb DJ, Salsbury J, Morant S, Ford I - BMJ Open (2015)

Trial schematic.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4539390&req=5

BMJOPEN2015008086F2: Trial schematic.
Mentions: Diuretics and new-onset diabetes: A major attraction of K+-sparing diuretics is the possibility that they will offset the diabetogenic potential of thiazides. Since they have not been compared in hypertension outcome trials, and diabetes (DM) has not been an end point in heart failure studies of spironolactone or eplerenone, we do not know for certain whether they are clean in this respect. Short-term studies suggest they are.10 Interestingly in INSIGHT there was no excess of DM in patients receiving hydrochlorothiazide (HCTZ) 25 mg, which was combined with amiloride 2.5 mg, but increased by 30% in patients on HCTZ/amiloride 50/5 mg.6 In PATHWAY-3, we use the oral glucose tolerance test (OGTT) to provide an end point for each subject. This strategy was previously used to demonstrate a difference after just 12 weeks of dosing with a thiazide diuretic.11 In the STAR study, which compared 200 markedly obese patients randomly assigned to either ACE inhibitor +Ca++ blocker, or ARB+thiazide, the subjects had impaired glucose tolerance at entry, allowing detection of changes on low-dose thiazide. Subsequently, two small crossover studies in about 40 patients showed a rise in 2 h glucose within 4 weeks of treatment with bendroflumethiazide 5 mg or HCTZ 50 mg, with a highly significant difference from the 2 h glucose during 4 weeks of treatment with amiloride 20 mg (figures 1 and 2).12

Bottom Line: We hypothesised that a K(+)-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K(+)-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide.The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24.PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19.

View Article: PubMed Central - PubMed

Affiliation: Clinical Pharmacology Unit, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK Trial Executive for the British Hypertension Society's PATHWAY Programme of Trials Steering Committee for the British Hypertension Society's PATHWAY Programme of Trials.

No MeSH data available.


Related in: MedlinePlus