ABSTRACT
INTRODUCTION: Gabapentin and pregabalin (gabapentinoids) can be given with opioids for opioid-sparing and adjuvant analgesic effects. In the context of certain comorbidities and high dosages, coadministration of these agents can lead to respiratory depression or oversedation, necessitating naloxone administration. METHODS: A retrospective chart review from January 2015 to December 2017 was conducted to include patients who received naloxone and opioids with or without gabapentinoids. Exclusion criteria included pregnancy or having received naloxone in the emergency department, intensive care, or pediatrics units. The primary outcome was to characterize differences between groups regarding comorbidities, history of renal or hepatic dysfunction, history of SUD, opioid tolerance, initiation and dose appropriateness of gabapentinoids, and dose intensity of gabapentinoids and opioids. Secondary outcomes were concomitant CNS depressant use and naloxone episodes for documented respiratory depression. RESULTS: Of 126 patients who met inclusion criteria, 36 received opioids and gabapentinoids (gabapentinoid group) and 90 received opioids alone (nongabapentinoid group). There were 136 naloxone episodes between the 2 groups. More than 50% of the naloxone episodes in the gabapentinoid group involved opioids of at least 90 oral morphine mg equivalents. Respiratory depression accounted for 39% and 15.8% of the naloxone episodes in the gabapentinoid and nongabapentinoid groups, respectively. DISCUSSION: There may be increased naloxone episodes among patients receiving opioids and gabapentinoids. Future studies are needed to evaluate the incremental risk of respiratory depression and oversedation as it pertains to concomitant medication administration and patient-specific factors.
ABSTRACT
BACKGROUND: The World Health Organization estimates that diabetes is the seventh leading cause of death. Uncontrolled diabetes may cause severe consequences such as cardiovascular (CV) events (myocardial infarction, stroke, or CV mortality), lower-extremity amputations, and end-stage renal disease. Microvascular complications include retinopathy, autonomic and peripheral neuropathy, nephropathy, and diabetic ulcers. Major CV outcomes trials that were by the Food and Drug Administration for all new antihyperglycemia medications for patients at high risk for CV events were recently completed for all 4 US-marketed dipeptidyl peptidase-4 (DPP-4) inhibitors. OBJECTIVE: To present a comprehensive review of the clinical trials that evaluate macrovascular and microvascular complications reported with DPP-4 inhibitors in patients with type 2 diabetes mellitus. METHODS: In this review, we analyzed published articles in PubMed and Ovid databases between January 2008 and September 2019 that evaluated the effect of DPP-4 inhibitors on macrovascular and microvascular complications in patients with type 2 diabetes mellitus. RESULTS: A total of 18 studies, which included randomized controlled trials and meta-analyses were assessed. Current evidence demonstrates that the addition of DPP-4 inhibitors to standard antihyperglycemic and CV risk reduction treatment has not shown CV benefit relative to placebo in contrast to recently published studies for other medications within the glucagon-like peptide 1 agonist and sodium-glucose co-transporter 2 inhibitor classes. Notably, the potential risk for heart failure hospitalizations may exist for saxagliptin, and this effect is not extrapolated as a class effect. Based on our review, DPP-4 inhibitors may not influence microvascular complications in patients with diabetes. However, some studies have shown that saxagliptin and linagliptin may slow down the progression of albuminuria in patients with type 2 diabetes mellitus. The overall quality of the studies included in this review was high due to the inclusion of randomized controlled trials and meta-analyses. CONCLUSIONS: DPP-4 inhibitors were found to have a neutral effect on macrovascular and microvascular complications, with the exception of saxagliptin, which may increase the risk for heart failure hospitalizations.
