Trial reportThe Journal of clinical endocrinology and metabolism2026
Metformin Blunts Vascular Insulin Sensitivity After Exercise Training in Adults at Risk for Metabolic Syndrome.
Trial report in The Journal of clinical endocrinology and metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Trial
- Metformin attenuates metabolic insulin sensitivity and insulin-stimulated carbohydrate oxidation after high-intensity exercise training in adults at risk for metabolic syndrome.Diabetes, obesity & metabolism · 2026Trial
- Metformin Alters Exercise Training Induced Blood Pressure and Aortic Waveform Adaptations in Adults at Risk for Metabolic Syndrome.Journal of clinical hypertension (Greenwich, Conn.) · 2026Trial
- The effects of metformin and exercise training on cardiorespiratory, blood pressure, and metabolic adaptations across the spectrum of glucose dysregulation: a systematic review and meta-analysis.EClinicalMedicine · 2026Article
- Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
contextMetformin is the first-line pharmacotherapy for treating hyperglycemia, and it lowers cardiovascular disease risk. Prior work suggests that metformin can, however, interfere with metabolic adaptations to exercise. To date, no work has tested if metformin (Met) alters exercise training mediated vascular insulin sensitivity, and whether this is exercise intensity dependent.
objectiveThis work aimed to test the hypothesis that Met blunts vascular insulin sensitivity in an intensity-based manner among adults at risk for metabolic syndrome.
methodsIn a double-blind, placebo-controlled trial, participants were randomly assigned to low-intensity exercise plus placebo (∼55% VO2max 5d/wk, LoEx + PL, n = 22) or metformin (2000 mg/d, LoEx + Met, n = 21) and high-intensity exercise plus placebo (∼85% VO2max 5d/wk, HiEx + PL, n = 24) or metformin (HiEx + Met, n = 24) for 16 weeks. A 120-minute euglycemic-hyperinsulinemic clamp (40 mU/m2/min, 90 mg/dL) was conducted pre and post treatment to assess macrovascular insulin sensitivity via brachial artery flow-mediated dilation (%FMD, conduit artery) as well as microvascular insulin sensitivity using contrast-enhanced ultrasound (eg, microvascular blood volume [MBV, perfusion] and microvascular blood flow [MBF]). Fasting and clamp-derived glucose, insulin, inflammatory measures (eg, endothelin-1 [ET-1], tumor necrosis factor α [TNF-α], soluble receptor for advanced glycation end products [sRAGE]), and nitric oxide (nitrite/nitrate) were assessed. Aerobic fitness (maximal oxygen consumption [VO2max]) and body composition (dual-energy x-ray absorptiometry [DXA]) were also analyzed.
resultsLoEx + PL and HiEx + PL increased VO2max (both P < .05), while there was no change after LoEx + Met or HiEx + Met. Body fat was reduced following HiEx + PL and HiEx + Met only (both P < .05). Met blunted the increase in insulin-stimulated FMDallometric and MBF seen with LoEx + PL and HiEx + PL (P < .05). Met also attenuated the reductions in fasting glucose, ET-1, and TNF-α compared with LoEx + PL and HiEx + PL (P < .05).
conclusionMet blunts exercise training-mediated increases in vascular insulin sensitivity at the levels of conduit arteries and capillaries, in parallel with altered inflammation and glycemic benefits.
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