In 2018, 34.5% of U.S adults had prediabetes [2] which confers a substantial risk of progression to overt type 2 diabetes (T2DM) [3]. Nearly 90% of those with prediabetes are unaware they have it [4]. The problem with this is that in those aged 45 years, the lifetime risk of progression from prediabetes to T2DM is 74.0% [4]. Better detection is certainly needed. But what can providers do when it is detected? The ADA recommendations to treat prediabetes include lifestyle and the medication metformin, although it is not approved by the Food and Drug Administration (FDA) for prediabetes [5]. Is this enough for a condition that is associated with an increased risk for all cause mortality and cardiovascular disease?

We have an obesity epidemic which has been driving up the prevalence of T2DM as well for which the treatment landscape has changed dramatically over the past few years due to the advent of glucagon-like peptide-1 (GLP-1) medications. The latest study to show beneficial effects of GLP-1 medications on progression to T2DM in patients with prediabetes is a phase 3 double-blind randomized controlled trial by Jastreboff and colleagues [6]. This study is an extension of the tirzepatide trial SURMOUNT-1 in a subset of 1032 participants with obesity and prediabetes who either continued once weekly tirzepatide or placebo for a total of 176 weeks followed by a 17-week off treatment period. The results showed that 10 participants (1.3%) randomized to pooled tirzepatide groups developed T2DM versus 36 (13.3%) in the placebo group, representing a 93% reduction (HR of 0.07) in the risk of developing T2DM. Depending on the dose of tirzepatide, weight losses were between 12.3 and 19.7%. During the 17 week off treatment period, an average 7% weight regain was observed, and an additional 8 participants from the tirzepatide group developed T2DM for a total of 18 participants (2.4%) as compared with 37 placebo participants (13.7%). Further, 15.5% of patients reverted from normoglycemia back to prediabetes.