Beneficial Effects of Pentoxifylline Plus Losartan Dual Therapy in Type 2 Diabetes with Nephropathy

Am J Med Sci. 2018 May;355(5):442-448. doi: 10.1016/j.amjms.2017.12.015. Epub 2018 Feb 1.

Abstract

Background: This study was designed to comparatively assess the effects of add-on pentoxifylline to losartan versus increasing the dose of losartan on serum N-terminal pro-brain natriuretic peptide (NT-proBNP), serum highly sensitive C-reactive protein (hsCRP) and the urinary albumin excretion (UAE) rate in patients with type 2 diabetes and nephropathy.

Methods: In an open-label, single-center, parallel-group, randomized clinical trial (NCT03006952), 30 patients received b.i.d. dose of pentoxifylline 400mg plus daily dose of losartan 50mg (pentoxifylline arm) and 29 patients received b.i.d. dose of losartan 50mg (losartan arm) during a 12-week follow-up period.

Results: Serum NT-proBNP, serum hsCRP and UAE levels all significantly decreased from baseline in both trial arms. The pentoxifylline and losartan trial arms were equally effective in reducing serum NT-proBNP levels during the course of trial (multivariable adjusted model P value = 0.864, effect size = 0.2%). There was a greater decrease in UAE and serum hsCRP levels in the pentoxifylline arm (P = 0.034, effect size = 7.8%; P = 0.009, effect size = 11.7%, respectively). Conversely, patients in the losartan arm achieved better systolic and diastolic blood pressure control (P < 0.001, effect size = 25.4%; P = 0.010, effect size = 11.3%, respectively).

Conclusions: Circulating NT-proBNP levels equally and significantly reduced from baseline in the pentoxifylline and losartan treatment arms, in parallel with comparatively superior decreases of UAE and serum hsCRP in the pentoxifylline arm, and larger decreases of systolic and diastolic blood pressures in the losartan arm.

Keywords: Highly sensitive C-reactive protein; N terminal pro-brain natriuretic peptide; NT-proBNP; Pentoxifylline; Urinary albumin excretion.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atrial Natriuretic Factor / blood
  • C-Reactive Protein / analysis
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Losartan / administration & dosage
  • Losartan / therapeutic use*
  • Male
  • Middle Aged
  • Pentoxifylline / administration & dosage
  • Pentoxifylline / therapeutic use*
  • Protein Precursors / blood
  • Serum Albumin, Human / urine
  • Treatment Outcome

Substances

  • N-terminal proatrial natriuretic peptide
  • Protein Precursors
  • Atrial Natriuretic Factor
  • C-Reactive Protein
  • Losartan
  • Pentoxifylline
  • Serum Albumin, Human