linagliptin and Diabetic-Neuropathies

Topics: Benzhydryl Compounds; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Humans; Hypoglycemic Agents; Linagliptin; Telmisartan

To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes.. Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial.. Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey.. Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function.. One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%.. ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with pre-diabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes.. - ClinicalTrials.Gov Identifier: NCT03222765 - EUDRACT Registry Number: 2013-000418-39.

Topics: Aged; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Double-Blind Method; Europe; Female; Galvanic Skin Response; Humans; Hyperglycemia; International Cooperation; Life Style; Linagliptin; Male; Metformin; Microcirculation; Middle Aged; Patient Selection; Research Design; Risk Factors

Chronic pain is a common complication of diabetes. The aim of the present study was to characterise pain behaviour in a high fat diet/streptozotocin (HFD/STZ) model of diabetes in the rat, investigate spinal mechanisms, and determine the effects of antidiabetic interventions. Three-week consumption of a high fat diet followed by single injection of STZ (45 mgkg(-1)) produced sustained changes in plasma insulin and glucose until day 120. Hindpaw mechanical withdrawal thresholds were significantly lowered in the model, but mechanically evoked responses of spinal neurones were unaltered, compared to HFD/vehicle rats. HFD/STZ rats had significantly lower numbers of spinal Iba-1 positive cells (morphologically identified as activated microglia) and spinal GFAP immunofluorescence (a marker of astrogliosis) in the spinal cord at day 50, compared to time-matched controls. The PPARγ ligand pioglitazone (10 mgkg(-1)) did not alter HFD/STZ induced metabolic changes or hindpaw withdrawal thresholds of HFD/STZ rats. Daily linagliptin (3 mgkg(-1)) and metformin (200 mgkg(-1)) from day 4 after model induction did not alter plasma glucose or insulin in HFD/STZ rats but significantly prevented changes in the mechanical withdrawal thresholds. The demonstration that currently prescribed antidiabetic drugs prevent aberrant pain behaviour supports the use of this model to investigate pain mechanisms associated with diabetes.

Topics: Animal Feed; Animals; Behavior, Animal; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Diet, High-Fat; Glial Fibrillary Acidic Protein; Hypoglycemic Agents; Insulin; Linagliptin; Male; Metformin; Microscopy, Fluorescence; Neuroglia; Neurons; Pain; Pain Management; Pain Measurement; Pioglitazone; PPAR gamma; Purines; Quinazolines; Rats; Rats, Sprague-Dawley; Thiazolidinediones