NDLI: Metformin may adversely affect orthostatic blood pressure recovery in patients with type 2 diabetes: substudy from the placebo-controlled Copenhagen Insulin and Metformin Therapy (CIMT) trial

Content Provider	Springer Nature : BioMed Central
Author	Hansen, Christian Stevns Lundby-Christiansen, Louise Tarnow, Lise Gluud, Christian Hedetoft, Christoffer Thorsteinsson, Birger Hemmingsen, Bianca Wiinberg, Niels Sneppen, Simone B. Lund, Søren S. Krarup, Thure Madsbad, Sten Almdal, Thomas Carstensen, Bendix Jørgensen, Marit E.
Abstract	Background Metformin has been shown to have both neuroprotective and neurodegenerative effects. The aim of this study was to investigate the effect of metformin in combination with insulin on cardiovascular autonomic neuropathy (CAN) and distal peripheral neuropathy (DPN) in individuals with type 2 diabetes (T2DM). Methods The study is a sub-study of the CIMT trial, a randomized placebo-controlled trial with a 2 × 3 factorial design, where 412 patients with T2DM were randomized to 18 months of metformin or placebo in addition to open-labelled insulin. Outcomes were measures of CAN: Changes in heart rate response to deep breathing (beat-to-beat), orthostatic blood pressure (OBP) and heart rate and vibration detection threshold (VDT) as a marker DPN. Serum levels of vitamin B12 and methyl malonic acid (MMA) were analysed. Results After 18 months early drop in OBP (30 s after standing) was increased in the metformin group compared to placebo: systolic blood pressure drop increased by 3.4 mmHg (95% CI 0.6; 6.2, p = 0.02) and diastolic blood pressure drop increased by 1.3 mmHg (95% CI 0.3; 2.6, p = 0.045) compared to placebo. Beat-to-beat variation decreased in the metformin group by 1.1 beats per minute (95% CI − 2.4; 0.2, p = 0.10). Metformin treatment did not affect VDT group difference − 0.33 V (95% CI − 1.99; 1.33, p = 0.39) or other outcomes. Changes in B12, MMA and HbA1c did not confound the associations. Conclusions Eighteen months of metformin treatment in combination with insulin compared with insulin alone increased early drop in OBP indicating an adverse effect of metformin on CAN independent of vitamin B12, MMA HbA1c. Trial registration The protocol was approved by the Regional Committee on Biomedical Research Ethics (H–D-2007-112), the Danish Medicines Agency and registered with ClinicalTrials.gov (NCT00657943).
Related Links	https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-020-01131-3.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	14752840
DOI	10.1186/s12933-020-01131-3
Journal	Cardiovascular Diabetology
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2020-09-26
Access Restriction	Open
Subject Keyword	Diabetes Angiology Cardiology Type 2 diabetes Metformin Autonomic neuropathy Orthostatic blood pressure recovery Complications Peripheral neuropathy Orthostatic hypotension Cardiovascular autonomic neuropathy
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Internal Medicine Endocrinology, Diabetes and Metabolism
Journal Impact Factor	8.5/2023
5-Year Journal Impact Factor	8.9/2023

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