Current and emerging pharmacotherapy for prediabetes: are we moving forward?

ABSTRACT

Introduction: Prediabetes is a state wherein blood glucose levels are above normal but below the diagnostic threshold for diabetes. Seventy percent of patients with prediabetes develop type 2 diabetes in their lifetime. Despite this, prediabetes frequently goes undiagnosed.

Areas covered: This review focuses on the pharmacological treatment of prediabetes and the prevention of progression to diabetes. A literature search was carried out on PubMed and Embase to review randomized controlled trials examining treatment of prediabetes. Emerging pharmacological therapies with potential benefit are discussed.

Expert opinion: Lifestyle intervention is the cornerstone for preventing progression to diabetes, but metformin remains the first line pharmacological intervention. There appears to be minimal additive effect of combining metformin with lifestyle changes. It would be interesting to assess whether using combination pharmacological approaches plus or minus lifestyle interventions have any additive benefit. Despite the good level of evidence available, the penetrance of any interventions remains very low in part due to the prodromal categorization of the prediabetic state.

KEYWORDS:

• Prediabetes
• diabetes
• pharmacotherapy
• metformin
• GLP-1

Article highlights

• Seventy percent of patients with prediabetes will progress to type 2 diabetes in their lifetime. Despite this, prediabetes frequently goes undiagnosed and untreated.

• Lifestyle intervention is the cornerstone for preventing progression to type 2 diabetes

• There are several large multicenter RCT investigating the effect of pharmacological intervention on prediabetes.

• Metformin remains the first line pharmacological intervention although there appears to be minimal additive effect of combining metformin with lifestyle changes.

• Liraglutide, a-glucosidase inhibitors, glitazones, and orlistat show benefit in prediabetes treatment. However, these treatments are typically compared to a placebo with a 500 kcal deficit diet and 150 min of exercise rather than very intensive lifestyle programs.

• Future research should assess whether using combination pharmacological approaches plus very intensive lifestyle interventions have an additive benefit.

This box summarizes key points contained in the article.

Declaration of Interest

C Le Roux has received grants from Johnson & Johnson and AnaBio Technologies Limited in addition to honoraria for lecturing and advisory work from Eli Lilly & Company, Johnson & Johnson, Sanofi, AstraZeneca, Bristol-Myers Squibb, and Boehringer Ingelheim. He also declares that he serves on the advisory board of GI Dynamics and Novo Nordisk. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Irish Research Council [EPSPD/2017/116], and [IRCLA/2017/234]; Science Foundation Ireland [12/YI/B2480]; and the Irish Health Research Board [USIRL-2016-2], and [ILP-HSR-2017-007].