Medications Affecting the Biochemical Conversion to Type 2 Diabetes: A Systematic Review and Meta-Analysis

Context: The extent to which some pharmacological interventions reduce or increase the risk of biochemical conversion to type 2 diabetes mellitus (T2DM) in at-risk individuals is unclear. Methods: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus through 24 August 2017 for randomized controlled trials evaluating the effect of drugs suspected to modify the risk of biochemical conversion to T2DM. Results: We included 43 trials with 192,156 subjects (mean age, 60 years; 56% men; mean body mass index, 30.4 kg/m(2)). alpha-Glucosidase inhibitors, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, metformin, orlistat, phentermine/topiramate, and pioglitazone significantly reduced the risk of biochemical conversion to T2DM, whereas statins and nateglinide increased the risk. There was insufficient direct evidence regarding the effects of sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors. Most trials were brief and evaluated this outcome during treatment without a withdrawal or washout period. Conclusions: Several drugs modify the risk of biochemical conversation to T2DM, although whether this effect is persistent and clinically relevant is unclear. Future studies need to focus on cardiovascular disease prevention, mortality, and patient-important outcomes instead of biochemical conversion to T2DM.