Evaluation of Dipeptidyl Peptidase-4 Inhibitors versus Thiazolidinediones or Insulin in Patients with Type 2 Diabetes Uncontrolled with Metformin and a Sulfonylurea in a Real-World Setting.

BACKGROUND: Guidelines do not make clear recommendations for third add-on agents to metformin plus a sulfonylurea. This study compared the effectiveness and safety of dipeptidyl peptidase-4 inhibitors (DPP4is) to thiazolidinedione (TZD) or insulin as a third add-on agent to metformin plus a sulfonylurea in an integrated health care setting. METHODS: This retrospective database cohort study included adults with type 2 diabetes not at goal hemoglobin A1C (HbA1C) who initiated DPP4i, TZD, or insulin as a third add-on agent to metformin plus a sulfonylurea from January 2006 to June 2016. Primary outcomes were the proportion of patients who achieved goal HbA1C after starting the third add-on agent and change in HbA1C. Subgroup analysis was performed for patients with baseline HbA1C greater than 9%. RESULTS: In this study, 2080 patients started on a DPP4i were matched to 8320 patients started on TZD and to 8320 patients taking insulin. A significantly higher percentage of patients taking TZD reached goal HbA1C (31.0% versus 23.6%; p < 0.05) and had a significantly larger HbA1C reduction (-0.94% ± 1.34% versus -0.79% ± 1.23%; p < 0.01) compared to patients taking a DPP4i. No difference in the percentage of patients meeting goal HbA1C nor in change in HbA1C was demonstrated between insulin versus DPP4i regimens. For patients with baseline HbA1C greater than 9%, insulin or TZD resulted in a significantly higher proportion of patients achieving goal HbA1C compared to DPP4i (17.3% and 19.0% versus 12.4%, respectively; p < 0.01). CONCLUSION: TZD was more effective than DPP4i but DPP4i was as effective as insulin as a third add-on agent in the overall study population. Insulin was more effective than DPP4i only in the subgroup analysis of patients with baseline HbA1C greater than 9%.

Evaluation of Outcomes After Initiating Triple Antidiabetic Therapy with a GLP-1 RA in an Integrated Health Care System.

BACKGROUND: Type 2 diabetes (T2D) is characterized by chronic hyper-glycemia and can lead to life-threatening complications if not treated. A stepwise and patient-centered approach is recommended when managing patients with T2D. Metformin is the preferred first-line agent, while sulfonylureas (SU) are often chosen as second-line agents. If a patient's hemoglobin A1c (A1c) goal is not achieved despite 3 months of treatment with dual therapy, then triple therapy is recommended. However, due to the lack of head-to-head trials for different triple antidiabetic regimens, the recommendations are unclear for selection of an optimal third-line agent. OBJECTIVE: To evaluate the comparative effectiveness of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) compared with a thiazolidinedione (TZD) or insulin as a third-line add-on therapy in patients who have not achieved A1c goals while receiving metformin and SU dual therapy in the real-world setting within an integrated health care system. METHODS: This is a retrospective cohort study of adult patients with T2D who were not at goal A1c while on dual therapy with metformin and an SU and initiated triple antidiabetic therapy. The primary outcome was the proportion of patients who achieved goal A1c within 3-7 months after starting triple therapy with a GLP-1 RA compared with a TZD or insulin. Goal A1c was defined as an A1c of < 7% for patients aged less than 65 years and A1c of < 8% for patients aged 65 years or older. Secondary outcomes included mean change in A1c, mean change in weight, and the proportion of patients with an emergent health care encounter due to a hypoglycemic event. Propensity score matching was used to select comparison groups from the insulin and TZD groups with similar baseline characteristics to the GLP-1 RA group in a 4:1 ratio. RESULTS: 274 patients initiated a GLP-1 RA in addition to dual therapy with metformin and an SU. A propensity matched group of 1,096 patients who initiated insulin and 1,096 patients who initiated a TZD were selected as the control groups. Addition of a GLP-1 RA resulted in a significantly lower proportion of patients achieving goal A1c (23.0%) compared with the addition of a TZD (30.8%, P = 0.011). There was no significant difference with the addition of a GLP-1 RA when compared with insulin (24.1%, P = 0.704). CONCLUSIONS: This study reflects data from real-world practice in a large integrated health care system. Significantly less patients achieved goal A1c with the addition of a GLP-1 RA as a third-line add-on option to dual therapy with metformin and an SU compared with the addition of a TZD. Providers and patients should carefully weigh the risks and benefits of different antidiabetic agents when choosing triple therapy regimens. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. Part of this study was presented as a nonreviewed resident poster at the Academy of Managed Care & Specialty Pharmacy Annual Meeting 2017 in Denver, CO, on March 27-29, 2017.

Dietary Supplement-Drug Interaction-Induced Serotonin Syndrome Progressing to Acute Compartment Syndrome.

BACKGROUND Dietary supplements have been associated with an increase in emergency intervention as a result of unexpected adverse events. Limited resources and information on significant drug-drug interactions with dietary supplements and prescription medications have contributed to associated complications and unexpected events. We present the case of a patient who consumed multiple prescription medications and dietary supplements which resulted in significant complications. CASE REPORT A 28-year-old man presented to the Emergency Department complaining of severe calf pain after exercising. In addition to his prescription medications, which included sertraline, he also consumed dietary supplements prior to his workout. He developed serotonin syndrome with rhabdomyolysis, which rapidly progressed to acute compartment syndrome. An emergency bilateral four-compartment double-incision lower extremity and forearm fasciotomy was performed, with complete recovery. CONCLUSIONS Drug-drug interactions involving dietary supplements are frequently overlooked in most healthcare settings, especially in the Emergency Department. Health care providers should be cognizant of the potential drug- drug interactions resulting in serotonin syndrome to prevent the progression to acute compartment syndrome and associated complications. Pharmacists play a key role in recognizing drug-dietary supplement interactions and adverse effects.