Fig. 2: Metformin treatment increases serum Lac-Phe.
From: Metformin and feeding increase levels of the appetite-suppressing metabolite Lac-Phe in humans
a, Spearmanʼs rank correlation between metformin and Lac-Phe levels in obese T2D individuals (n = 8) for the Brigham and Women’s Hospital cohort. Graph shows mean linear regression with 95% confidence intervals. One volunteer (highlighted with an arrow) had stopped taking their metformin medication. b, TwinsUK volunteers provided three serum samples, with an average of 6.5 years between samples. Paired data are shown for volunteers whose T2D status changed and/or who commenced metformin treatment between samples (***P = 0.0002 and ****P < 0.0001; NS, non-significant). c, Volcano plot comparing metabolomes in T2D volunteers with (n = 71) and without (n = 91) metformin treatment. Metabolites significantly upregulated (blue) and downregulated (red) with metformin treatment are shown, and N-lactoyl amino acids and metformin are labelled. d, Spearmanʼs rank correlation in T2D samples (n = 162) versus non-metabolite metadata (Years T2D, years since T2D diagnosis; Non-fasted, volunteer had eaten within 6 h of sample collection; >5yr T2D, more than 5 years since T2D diagnosis; BMI, body mass index of volunteer; VitC in serum, ascorbate detected in metabolomics; Age at diagnosis, age when volunteer received a T2D diagnosis). e, Comparison of amino acid (AA) and N-lactoyl-amino acid (N-lactoyl-AA) levels after a 12-week metformin intervention, relative to pre-treatment levels, in a 2019 Danish study (NCT01729156). Fold increases for patients with recent-onset T2D and age/BMI-matched non-T2D controls (n = 12 per group) showing five separate AAs and the corresponding N-lactoyl-AA; phenylalanine (circle), tyrosine (square), valine (hexagon), leucine (triangle) and isoleucine (diamond) (*P < 0.05). f, Lac-Phe levels (relative to baseline) over 36 h after a single oral dose of metformin in a study involving 26 young healthy male volunteers. Lac-Phe values measured before the maximum metformin concentration (Cmax) in the serum, at the Cmax and after the Cmax. A final sample was taken 36 h after dosing (**P = 0.0086, ***P = 0.0005 and ****P < 0.0001). Data are individual data points (a,f), individual paired data points (b) and mean values (e). Data were analysed using two-way ANOVA with Fisher’s LSD post test (b), two-tailed Student’s t-test (c), Welch’s two-sided Student’s t-test (e) and one-sample t-test against a theoretical value of 1 (f). Brigham cohort, Brigham and Women’s Hospital cohort.
