IntroductionWhen first line therapy with metformin is insufficient for patients with type 2 diabetes (T2D), the optimal adjunctive therapy is unclear. We assessed the efficacy and safety of adjunctive antidiabetic agents in patients with inadequately controlled T2D on metformin alone.Materials and MethodsA search of MEDLINE and CENTRAL, clinicaltrials.gov, regulatory websites was performed. We included randomized controlled trials of 3–12 months duration, evaluating Food and Drug Administration or European Union approved agents (noninsulin and long acting, once daily basal insulins) in patients experiencing inadequate glycemic control with metformin monotherapy (≥1500 mg daily or maximally tolerated dose for ≥4 weeks). Random-effects network meta-analyses were used to compare the weighted mean difference for changes from baseline in HbA1c, body weight (BW) and systolic blood pressure (SBP), and the risk of developing hypoglycemia, urinary (UTI) and genital tract infection (GTI).ResultsSixty-two trials evaluating 25 agents were included. All agents significantly reduced HbA1c vs. placebo; albeit not to the same extent (range, 0.43% for miglitol to 1.29% for glibenclamide). Glargine, sulfonylureas (SUs) and nateglinide were associated with increased hypoglycemia risk vs. placebo (range, 4.00–11.67). Sodium glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 analogs, miglitol and empagliflozin/linagliptin significantly reduced BW (range, 1.15–2.26kg) whereas SUs, thiazolindinediones, glargine and alogliptin/pioglitazone caused weight gain (range, 1.19–2.44kg). SGLT2 inhibitors, empagliflozin/linagliptin, liraglutide and sitagliptin decreased SBP (range, 1.88–5.43mmHg). No therapy increased UTI risk vs. placebo; however, SGLT2 inhibitors were associated with an increased risk of GTI (range, 2.16–8.03).ConclusionsAdding different AHAs to metformin was associated with varying effects on HbA1c, BW, SBP, hypoglycemia, UTI and GTI which should impact clinician choice when selecting adjunctive therapy.

Aim: To describe the epidemiologic, humanistic and economic burdens of hepatocellular carcinoma (HCC) in the USA. Materials & methods: Studies describing the epidemiology and economic burden from national cohorts, any economic models, or any humanistic burden studies published 2008–2018 were systematically searched. Results: HCC incidence was 9.5 per 100,000 person-years in most recent data, but was ∼100-times higher among patients with hepatitis/cirrhosis. Approximately a third of patients were diagnosed with advanced disease. Patients with HCC experienced poor quality of life. Direct costs were substantial and varied based on underlying demographics, disease stage and treatment received. Between 25–77% of patients did not receive surgical, locoregional or systemic treatment. Conclusion: Better treatments are needed to extend survival and improve quality of life for patients with HCC.

A55oral agents only (43%), and 25% contained insulin. Of patients using CANA in combination with other AHAs, 20% discontinued use of at least 1 AHA during followup. CANA index dose was 100mg for 65% of the population and 300mg for the remainder; 30% of patients initially observed on CANA 100mg titrated to 300mg. Among patients with A1C ≥ 7.0% at baseline, the proportion of patients with A1C < 7% and < 8% increased from 0% (baseline) to 21% (follow-up) and 30% (baseline) to 61% (follow-up), respectively; those with A1C ≥ 9.0% decreased from 33% (baseline) to 16% (follow-up). CONCLUSIONS: CANA was often prescribed as add-on therapy to multiple AHAs with one-fifth of patients discontinuing use of other AHAs after CANA was added to their treatment regimen. In patients with uncontrolled A1Cs, their A1Cs improved following treatment with CANA.

BackgroundPancreatic cancer represents the third leading cause of US cancer deaths, with median survival <1 year. The goal of this study was to describe systemic treatments, healthcare utilization and costs, and overall survival among patients with unresectable/metastatic disease.MethodsThis study used healthcare claims for commercial and Medicare Advantage enrollees diagnosed with pancreatic adenocarcinoma (at index date) during January 01 2010 to 31 May 2017. Included patients were aged ≥18 years, with continuous 6‐month preindex enrollment. Patients were excluded by resectable disease, another primary cancer, or pregnancy. Cohorts were based on first‐line (LOT1) chemotherapy regimen.ResultsOverall, 12 978 patients (mean age 70 years, 51% male) were included, among which 5610 (43%) received chemotherapy. Of those, 23% received gemcitabine monotherapy, 22% gemcitabine‐nab paclitaxel, 22% FOLFIRINOX, 3% FOLFOX, and 29% received other regimens. Mean LOT1 duration was 112 days; 60% did not undergo subsequent lines of therapy. Moreover, 50% of patients had an emergency room visit and 45% were hospitalized during LOT1. Among treated and untreated patients, mean total 6‐month costs were $52 101. We found that patients receiving FOLFIRINOX had the highest costs, whereas those who received gemcitabine monotherapy had the lowest. Median overall survival (mOS) was 335 days with any first‐line treatment. FOLFIRINOX‐treated patients had the highest mOS (492 days), whereas gemcitabine monotherapy‐treated patients had the lowest (223 days).ConclusionsA large proportion (57%) of patients with unresectable/metastatic pancreatic cancer did not receive chemotherapy. Healthcare costs were higher for fluorouracil‐based regimens, while lower for gemcitabine‐based regimens. Survival rates were within expectations for advanced pancreatic cancer.

Aims: Determine the efficacy and safety of antidiabetic agents added-on to metformin and a thiazolidinedione (TZD) in patients with inadequately controlled type 2 diabetes (T2D). Methods: MEDLINE and CENTRAL were searched for randomised controlled trials (RCTs) evaluating the addition of an antidiabetic agent in patients with T2D inadequately controlled on stable, optimised metformin and TZD therapy (≥ 1500 mg metformin and ≥ 50% maximum TZD dose for ≥ 4 weeks). Frequentist network meta-analysis was performed on identified studies. Results: Eleven RCTs evaluating dipeptidyl peptidase-4 inhibitors (linagliptin, sitagliptin), sulfonylureas (SUs) (glibenclamide, glimepiride), glucagon-like peptide-1 (GLP-1) analogues (exenatide, liraglutide, dulaglutide, taspoglutide) and sodium-glucose cotransporter2 (SGLT2) inhibitors (canagliflozin, empagliflozin) were identified. The mean reduction in HbA1c from baseline was significant for all agents (range, 0.55-1.17%) vs. placebo. SUs were associated with weight gain (range, 3.31-7.29 kg), while weight loss was seen with all GLP-1 analogues (range, 1.53-2.20 kg) and SGLT2 inhibitors (range, 2.08-2.95 kg) vs. placebo. Relative risk of hypoglycaemia was increased with dulaglutide, exenatide and glimepiride vs. placebo (RR range, 2.65-6.17); and trended higher with all other agents except linagliptin. GLP-1 analogues and canagliflozin reduced systolic blood pressure vs. placebo (range, 2.39-5.05 mmHg). No agent with available data increased the risk of urinary or genital tract infection vs. placebo. Conclusion: When added to stable, optimised metformin and TZD, all evaluated antidiabetic agents reduced HbA1c; albeit not to the same degree. Moreover, agents differed in their effects on body weight, hypoglycaemia and systolic blood pressure. Review criteria• A systematic literature search was conducted in MEDLINE and Cochrane CENTRAL through 8 January 2015.• Randomised controlled trials (RCTs) evaluating adults with type 2 diabetes inadequately controlled on metformin plus a thiazolidinedione (TZD) were included if the trial compared a noninsulin drug or long-acting, once-daily basal insulin to another of these therapies or placebo and reported change in glycosylated haemoglobin A1c.• Frequentist network meta-analyses were performed on 11 identified RCTs. Message for the clinic• Ten therapies were evaluated in the following classes: dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas (SUs), glucagon-like peptide-1 (GLP-1) analogues and sodium-glucose cotransporter2 (SGLT2) inhibitors.• All individual agents reduced HbA1c when added to stable metformin plus TZD therapy, but not to the same degree.• SGLT2 inhibitors and GLP-1 agonists significantly reduced weight compared with DPP-4 inhibitors, SUs and placebo. No agent resulted in an increased risk of urinary or genital tract infection compared with placebo.