Background:National treatment guidelines recommend glucagon-like peptide receptor agonists (GLP-1 RAs) as add-on therapy to oral agents. However, GLP-1 RAs in combination with dipeptidyl peptidase-4 (DPP-4) inhibitors is not recommended due to a lack of evidence.Objective:This case series aims to describe the efficacy and safety of once-weekly GLP-1 RAs administered concomitantly with DPP-4 inhibitors in patients with type 2 diabetes.Methods:A retrospective chart review of electronic medical records at a free health clinic was conducted between July 2014 and September 2016. Patients 18 years and older with type 2 diabetes were included if they received concomitant DPP-4 inhibitor and once-weekly GLP-1 RA therapy with at least one glycated hemoglobin A1c (HbA1c) measurement within three to six months of starting the combination. The primary and secondary outcomes included change in HbA1c and weight, and patient reported adverse events.Results:Out of forty-three patients that received combination DPP-4 inhibitor plus GLP-1 RA therapy, only eighteen received once-weekly GLP-1 RA. At 3 months, the median (IQR) HbA1c and weight change was -0.8% (-4.3 to 2%) and -0.4kg (-4.2 to 5.8 kg) respectively. No patients reached an HbA1c below 7% and only three patients (17%) reached a HbA1c less than 8%. Patient reported adverse effects included gastrointestinal disturbances (28%), hypoglycemic symptoms (17%), and injection site reactions (0.6%).Conclusions:Concomitant use of once-weekly GLP-1 RAs and DPP-4 inhibitors provides only modest improvement in glycemic control with minimal weight loss benefits, which is similar to monotherapy with either agent. The combination is unlikely to provide synergistic effects and is not cost effective. These data support the current recommendations against use of combined incretin therapy.

In addition to statin utilization increasing in recent years, there is greater emphasis on using moderate to high-intensity statin doses. Statin-related adverse effects are often dose-dependent; therefore, patients may be at increased risk. Antimicrobial use has also increased in recent years, and various efforts have been implemented to ensure appropriate use of antimicrobials. Commonly used antimicrobials, such as macrolide antibiotics and azole antifungals, interact significantly with the CYP3A4 enzyme pathway similarly to lovastatin, simvastatin, and atorvastatin. Consequently, the potential for significant drug-drug interactions is increasing. In 2012, the US Food and Drug Administration strengthened warning labels for statins and dose adjustments related to drug-drug interactions. As such, it is imperative that clinicians are comfortable identifying drug-drug interactions between statins and antimicrobials and making appropriate therapy modifications as clinically warranted. Statins and antimicrobials are frequently coprescribed, and the available pharmacokinetic data supports the potential for clinically significant drug-drug interactions. Macrolides and selected antifungals can significantly increase drug levels of select statins, particularly those metabolized by the CYP3A4 pathway. Contrarily, rifampin can significantly reduce drug levels of statins, limiting their efficacy. Future research efforts should identify interventions to improve clinician recognition of these drug-drug interactions and the prevention of unwarranted statin-related adverse effects.

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