Metformin use in prediabetes: is earlier intervention better?
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ORIGINAL ARTICLE
Metformin use in prediabetes: is earlier intervention better? Andrew Warrilow1 · Shawn Somerset1 · Kate Pumpa1 · Robert Fleet2 Received: 24 April 2020 / Accepted: 12 June 2020 © Springer-Verlag Italia S.r.l., part of Springer Nature 2020
Abstract Aim The aim of this study was to investigate the effectiveness of metformin in diabetes prevention in a prediabetic population across a range of fasting plasma glucose (FPG) levels at baseline. A secondary aim was to assess the effectiveness of metformin in preventing diabetes in those participants where impaired fasting glucose (IFG) was relatively more pronounced as opposed to impaired glucose tolerance (IGT). Methods Participants randomised to metformin and placebo arms in the Diabetes Prevention Program study were stratified into cohorts according to level of FPG at baseline. Cumulative incidence of diabetes for the different cohorts was assessed. Change in FPG, insulin sensitivity, and levels of fasting insulin and proinsulin for the different cohorts were also calculated. Results The largest reductions in incidence of diabetes and FPG occurred within prediabetic persons with a higher level of FPG at baseline. Metformin was able to stabilise insulin sensitivity in every stratified sub-cohort except one. Sub-cohorts which had higher levels of insulin sensitivity at baseline experienced the largest increases in insulin sensitivity. Metformin reduced the incidence of diabetes by 43% (RR 0.57, CI 0.4–0.9) in those prediabetic persons whose IFG was more pronounced compared to a 26% (RR 0.74 CI 0.7–0.8) when all participants in the study were included. Conclusion The largest reductions in both incidence of diabetes and FPG occurred in prediabetic persons with a higher level of FPG at baseline. Metformin was able to stabilise insulin sensitivity and was more effective in persons with more pronounced IFG. Keywords Metformin · Prediabetes · Diabetes prevention · Insulin sensitivity · Insulin resistance
Introduction The International Diabetes Federation estimated that globally in 2017 there were 451 million people with diabetes worldwide, approximately half of whom are undiagnosed.
Managed by Massimo Porta. * Andrew Warrilow [email protected] Shawn Somerset [email protected] Kate Pumpa [email protected] Robert Fleet [email protected] 1
University of Canberra, Locked Bag 1, Canberra, ACT 2601, Australia
The Australian National University, Canberra, ACT 2600, Australia
2
In that year, 5 million deaths worldwide were attributable to diabetes and the global healthcare expenditure on people with diabetes was estimated to be US$850 billion [1]. A more effective pharmacologically based strategy for the prevention of type 2 diabetes would have significant benefits globally both for society and the economy. The Diabetes Prevention Program (DPP) randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, the drug metformin (850 mg twice daily), or
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