John R. Petrie, MD, PhD


September 22, 2017

Hi. I am John Petrie, from the 2017 European Association for the Study of Diabetes (EASD) in Lisbon. I am here to talk about new data on REMOVAL,[1] which is a trial of metformin in type 1 diabetes. While main data were presented at the American Diabetes Association (ADA) Scientific Sessions, we presented new data in a symposium on the first day of the EASD Congress. I wanted to speak about these new data, particularly renal [function] data, biomarker data, and subgroup analysis results that are relevant to the updated guidelines about metformin in type 1 diabetes.

Metformin is currently recommended by the ADA and other bodies in type 1 diabetes for obese people in order to try to control A1c and reduce insulin requirement.[2,3] The findings of REMOVAL originally cast doubt upon that recommendation but did show some effects on body weight, LDL cholesterol, and on atherosclerosis progression by a tertiary endpoint.[1]

We now have data showing that metformin actually reduces the attenuation of estimated glomerular filtration rate (eGFR) that you normally see in type 1 diabetes, with an effect size of about 1 mL/min/year of eGFR measured by cystatin C, not just by creatinine. So this is a robust finding. We also show a strong trend in the reduction of microalbuminuria as a categorical variable, and we are still doing the analysis on the albumin excretion rate. Peter Rossing presented a nice report on the renal data from REMOVAL.

We looked at the biomarkers. We found a reduction in tissue plasminogen activator of about 20%, a reduction in C-reactive protein of about 16%, LDL reduction, apolipoprotein B reduction, and that high-sensitivity troponin-T was unaffected.

We have looked in more detail at B12 deficiency, which is in the guidelines for metformin and type 1 diabetes in that B12 does go down in long-term treatment. In REMOVAL, the effects of hemoglobin were very minimal and probably not mediated by B12 deficiency because mean corpuscular volume was unaffected. Coen Stehouwer presented those data.

Finally, Helen Colhoun talked about the subgroup analysis, and we found no evidence for a threshold at which metformin is more or less effective above or below a body mass index (BMI) of 30, as claimed by the guidelines. The small effects in cholesterol, renal [function], and weight are really quite consistent across the board. If anything, people with a higher BMI have a lower A1c by 0.2% because they are on more insulin rather than less insulin.

These are the new data from the REMOVAL trial. Thanks for listening.


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