Clinical Question

Are dipeptidyl-peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists effective in preventing type 2 diabetes mellitus and its associated complications in patients at increased risk?

Evidence-Based Answer

There is only limited-quality evidence that at-risk patients taking GLP-1 receptor agonists are less likely to progress to diabetes (number needed to treat [NNT] = 23). Serious adverse events were more likely in patients taking GLP-1 receptor agonists than in patients taking placebo (number needed to harm [NNH] = 42). There is insufficient evidence to evaluate the effect of DPP-4 inhibitors on at-risk patients. There is no evidence that either medication class affects the development of diabetes-associated complications.¹ (Strength of Recommendation: C, based on low-quality, disease-oriented evidence.)

Practice Pointers

In the United States alone, an estimated 30.3 million persons have diabetes and 84.1 million have prediabetes,² and 70% to 90% of those with prediabetes progress to diabetes.³ Microvascular and macrovascular complications of diabetes begin to occur while patients are still in the prediabetic stage.^3,4 Metformin and acarbose (Precose) have been shown to decrease the risk of some of these complications, but data for other medications are lacking.^5,6

This Cochrane review included seven randomized controlled trials.¹ Because of the limited number of participants—only 98 patients—and the lack of patient-oriented outcomes data from the two DPP-4 inhibitor trials, no conclusions could be drawn about that class of medication. The remaining five trials included 1,620 participants randomized to monotherapy with a GLP-1 receptor agonist.

In a single randomized, double-blind, placebo-controlled trial, authors studied the effect of liraglutide (Victoza; a GLP-1 receptor agonist) in patients with prediabetes and obesity. After 160 weeks, fewer patients treated with liraglutide developed diabetes than those treated with placebo (1.8% vs. 6.2%; absolute risk reduction = 4.3%; NNT = 23). Because of limited data, no conclusions could be drawn regarding the effect of GLP-1 receptor agonists to decrease the risk of complications associated with diabetes.

Patients receiving GLP-1 receptor agonists may experience serious adverse events including, but not limited to, myocardial infarction, cholelithiasis, cholecystitis, pancreatitis, intervertebral disk protrusion, abdominal and hiatal hernia, infection, and neoplasm.⁷ More individuals who received liraglutide had serious adverse events than those who received placebo (15.1% vs. 12.7%; absolute risk increase = 2.4%; NNH = 42). It is noteworthy that most of the data on GLP-1 receptor agonists came from the same large industry-sponsored study. Because of the small number of participants in the other GLP-1 receptor agonist studies, no comparisons among the different agents and thus no conclusions regarding their relative benefit could be made.

Current guidelines for treating patients with prediabetes advocate lifestyle modification, optimizing comorbid conditions, and—in high-risk individuals—metformin to decrease progression to diabetes.^5,6 The American Diabetes Association acknowledges that other medications, including acarbose, orlistat (Xenical), GLP-1 receptor agonists, and thiazolidinediones, can decrease the incidence of progression to diabetes, but recommends metformin based on the strong evidence and long-term safety data.⁵