Effects of Low Doses of Captopril or Losartan in Improving Glycemic Control by Oral Hypoglycemic Agents in Type 2 DM Patients

Abstract

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
Cross-talk between the rennin-angiotensin system (RAS) and insulin signaling has been demonstrated. The rennin angiotensin system (RAS) may regulate
pancreatic islet blood flow, oxygen tension, and islet (pro) insulin biosynthesis.
The present study was designed to evaluate the effect of low doses captopril and losartan, as adjunct treatment in uncontrolled type 2 DM patients treated with oral hypoglycemic agents alone.
This double-blind placebo-controlled clinical trial was conducted on 75 patients with uncontrolled type 2 diabetes mellitus; they are randomized into three groups:
Group A: includes (25) patients treated with placebo formula containing lactose only in addition to glibenclamide (10 mg/kg) for 4 months; group B: includes
(25) patients treated with 12.5 mg captopril given once daily at bed time, for 4 months; group C: includes (25) patients treated with 25 mg losartan given as a
single daily dose at bed time for 4 months; all patients take the test drugs in addition to the routinely administered oral hypoglycemic drug (glibenclamide 10
mg/kg). After 12 hours fasting, blood samples were collected from all patients to measure fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), Cpeptide, triglyceride (TG), total cholesterol, low density lipoprotein (LDL-c), high density lipoprotein (HDL-c), serum urea and creatinine, alanine transaminase, aspartate transaminase, alkaline phosphatase (ALP) and gamma glutamine transferees (GGT), and urine samples were obtained for assessment of
microalbuminuria (MAU), before starting drug treatment (as zero time sample) and then after 4 months of treatment to follow the changes in the studied
parameters.
Adjuvant use of low doses of captopril or losartan with the currently used oral hypoglycemic agents (glibenclamide) results in significant reduction in FPG and HbA1c levels associated with increase in C-peptide level compared to those treated with the oral hypoglycemic agents and placebo; additionally, lipid profile, MAU, renal and liver functions were significantly improved after 4 months of treatment.
Inhibition of RAS by ACEIs or AT1 antagonists (ARBs) increases insulin sensitivity and improves insulin secretion, where treatment of poorly controlled type 2 DM patients with captopril or losartan resulted in improving the response of target tissues to glibenclamide.