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Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
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Clinical manifestationsPeripheral Arterial Disease (PAD) manifests through a range of symptoms, from the characteristic intermittent claudication to atypical presentations and severe complications in advanced stages. Intermittent claudication, a hallmark symptom of PAD, presents as exercise-induced muscle pain that typically resolves within minutes of rest. This pain is reproducible and stems from inadequate blood flow, leading to the accumulation of lactic acid produced during anaerobic...
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α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
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MetfOrmin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC): randomized clinical trial protocol.

Katherine M Reitz1,2,3, Andrew D Althouse4, Daniel E Forman5,6

  • 1Department of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.

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Metformin may improve walking distance and reduce inflammation in patients with peripheral artery disease (PAD) and intermittent claudication (IC). This study investigates its effects on function, PAD progression, and systemic inflammation in non-diabetic individuals.

Keywords:
Anti-inflammatory agentsAtherosclerosisClinical trial protocolIntermittent claudicationMetforminPeripheral artery disease

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Area of Science:

  • Vascular Medicine
  • Pharmacology
  • Exercise Physiology

Background:

  • Peripheral artery disease (PAD) affects over 230 million globally, characterized by atherosclerosis, inflammation, and hypertension.
  • Intermittent claudication (IC) is a common symptom of PAD, leading to mobility loss and increased cardiovascular risk.
  • Current treatments for PAD and IC are limited, necessitating novel therapeutic approaches.

Purpose of the Study:

  • To evaluate the efficacy of metformin in improving functional status in non-diabetic patients with IC.
  • To assess metformin's impact on PAD progression, systemic inflammation, and mitochondrial function.
  • To determine the effect of metformin on cardiovascular events and quality of life in PAD patients.

Main Methods:

  • A randomized, placebo-controlled trial involving 200 non-diabetic Veterans with IC.
  • Participants received 1000 mg/day of metformin extended-release or placebo for 180 days.
  • Primary outcome: change in 6-minute walk test (6MWT) distance; secondary outcomes included functional assessments, inflammatory markers, and cardiovascular events.

Main Results:

  • The study is designed to assess the primary outcome of 180-day maximum walking distance on the 6-minute walk test (6MWT).
  • Secondary outcomes encompass functional status, quality of life, lower extremity blood flow, and cardiovascular events.
  • Systemic inflammation markers and mitochondrial function will also be evaluated throughout the study.

Conclusions:

  • Metformin's anti-inflammatory and promitochondrial properties suggest potential benefits for PAD and IC.
  • The MOBILE IC trial aims to provide evidence for metformin as a novel therapeutic option for non-diabetic PAD patients.
  • Findings could lead to improved management strategies for PAD, enhancing patient mobility and cardiovascular health.