REMOVAL Update: More Benefits of Metformin in T1D

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.

Let's block ads! (Why?)

http://www.medscape.com/viewarticle/885883