Long-term safety and effectiveness of biosimilar insulin glargine in Japanese patients with diabetes mellitus in routine clinical practice: results of a post-marketing safety study

Abstract

Objective: To evaluate the long-term safety and effectiveness of biosimilar insulin glargine (GLY) in real-world clinical practice.

Methods: This prospective, non-interventional, multicenter, observational, post-marketing safety study (PMSS) enrolled Japanese patients with type 1 or 2 diabetes mellitus (T1DM or T2DM) starting GLY therapy, and was required by Japanese Pharmaceutical Affairs Law mandating post-marketing safety surveillance to acquire safety and effectiveness data of biosimilar products. Data collected from the 12-month observation included patient characteristics, adverse events, and blood glucose control.

Results: The study enrolled 141 patients with T1DM and 1104 patients with T2DM. Pre-study insulin was used by 94.1% of patients with T1DM and 75.0% with T2DM. 65.4% of patients with T1DM and 64.3% with T2DM switched from the reference product (GLY-switched), while 25.0% with T2DM were insulin-naive. Adverse events were reported by 5.7% and 8.5% in T1DM and T2DM, respectively. Similar incidences were reported in GLY-switched. Adverse events were reported by 10.7% in insulin-naive T2DM. Baseline mean hypoglycemic events/month were 1.8 and 0.1 in T1DM and T2DM, respectively: the mean change from baseline (CFB) was –1.2 (p?=?.066) and 0.0 (p?=?.915), respectively. Baseline mean HbA1c was 8.4% and 8.7% in T1DM and T2DM, respectively; the mean CFB was –0.5% (p?<?.001) and –0.9% (p?<?.001), respectively, and –1.5% (p?<?.001) in insulin-naive T2DM.

Conclusions: This first long-term Japanese PMSS of GLY demonstrated adverse events, hypoglycemia, and glycemic control consistent with the known GLY profile for T1DM and T2DM patients, in routine clinical practice.     

The effects of carnitine supplementation on clinical characteristics of patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials

ObjectiveThe beneficial effects of carnitine supplementation on nonalcoholic fatty liver disease are unclear. We conducted a systematic review and meta-analysis to evaluate the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance in patients with nonalcoholic fatty liver disease.MethodsA comprehensive search of PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases were performed. Only randomized placebo-controlled human studies that examined the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance up to September 2019 were included. Fixed effects or random-effects models were applied to compute the pooled effect size. Heterogeneity assessments were performed using Cochran’s Q test and I-squared statistics. The quality of the studies was assessed using the Jaded scale.ResultsA total of 5 articles were selected, including 334 individuals (167 in control and 167 in intervention groups). The results demonstrated that carnitine supplementation significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: −0.91; 95 % CI: −1.11, −0.72; p < 0.001, I² = 0.0 %) and the levels of aspartate aminotransferase (AST) (WMD: −16.62; 95 % CI: −28.11, −5.14; IU/l; p = 0.005, I² = 93.5 %), alanine aminotransferase (ALT) (WMD: -33.39; 95 % CI: −45.13, −21.66; IU/l; p < 0.001, I² = 93.4 %), and triglycerides (TG) (WMD: −22.13; 95 % CI: −38.91, −5.34; mg/dl; p = 0.01; I² = 0.0 %). However, the results of the pooled effect size did not show any significant effect of carnitine supplementation on body mass index (BMI) (WMD: 0.07; 95 % CI: −0.15, 0.29; p = 0.55; I² = 0.0 %), body weight (WMD: −0.28; 95 % CI: −2.23, 1.68; p = 0.78; I² = 45.7 %), the levels of gamma-glutamyl transferase (γGT) (WMD: −11.31; 95 % CI: −24.35, 1.73; IU/l; p = 0.09, I² = 61.1 %), cholesterol (WMD: −13.58; 95 % CI: −46.77, 19.60; mg/dl; p = 0.42; I² = 94.9 %), high-density lipoprotein-cholesterol (HDL-C) (WMD: 1.36; 95 % CI: −0.96, 3.68; mg/dl; p = 0.25; I² = 64.7 %), and low density lipoprotein-cholesterol (LDL-C) (WMD: −14.85; 95 % CI: −45.43, 15.73; mg/dl; p = 0.34; I² = 96.4 %).ConclusionsThis analysis shows that carnitine supplementation for patients with nonalcoholic fatty liver disease demonstrates a reduction in AST, ALT, TG levels and HOMA-IR. However, no significant effect of carnitine supplementation was observed on BMI, body weight, the levels of γGT, TC, HDL-cholesterol and LDL-cholesterol.     

Resistant Starch Content in Foods Commonly Consumed in the United States: A Narrative Review

Resistant starch (RS; types 1 to 5) cannot be digested in the small intestine and thus enters the colon intact, with some types capable of being fermented by gut microbes. As a fiber, types 1, 2, 3, and 5 are found naturally in foods, while types 2, 3, and 4 can be added to foods as a functional ingredient. This narrative review identifies RS content in whole foods commonly consumed in the United States. Scientific databases (n=3) were searched by two independent researchers. Ninety-four peer-reviewed articles published between 1982 and September 2018 were selected in which the RS was quantified and the food preparation method before analysis was suitable for consumption. The RS from each food item was adjusted for moisture if the RS value was provided as percent dry weight. Each food item was entered into a database according to food category, where the weighted mean±weighted standard deviation was calculated. The range of RS values and overall sample size for each food category were identified. Breads, breakfast cereals, snack foods, bananas and plantains, grains, pasta, rice, legumes, and potatoes contain RS. Foods that have been cooked then chilled have higher RS than cooked foods. Foods with higher amylose concentrations have higher RS than native varieties. The data from this database will serve as a resource for health practitioners to educate and support patients and clients interested in increasing their intake of RS-rich foods and for researchers to formulate dietary interventions with RS foods and examine associated health outcomes.     

Comparison of urinary amino acid excretory pattern in patients with type 2 diabetes mellitus and non-diabetic healthy controls at a tertiary referral hospital in India

AimSpecific amino acids have been linked to regulation of insulin secretion from pancreatic β-cells; on the contrary, increased concentration of certain amino acids is associated with insulin resistance (IR) and development of type 2 diabetes mellitus (T2DM). Nowadays, urine as a biological sample has attracted more attention for diagnosis of disease for its special superiority; insufficient research in the study of urinary amino acid (UAA) pattern in patients with T2DM has led to the present study with the aim to determine the levels of UAAs, their excretory patterns and the association of UAA to plasma glucose and IR in patients with T2DM.MethodsQuantification of total urinary amino acids was done spectrophotometrically and the patterns of amino acid excretion was elucidated by thin layer chromatography technique. Fasting blood samples were used for plasma glucose and insulin estimation by fully automated analyzer.ResultThe levels of UAA in patients with T2DM in comparison to healthy controls were higher (p < 0.0001). The frequency of urinary phenylalanine, arginine, tryptophan, tyrosine and cysteine were significantly higher in patients with T2DM than controls. There was also a strong positive correlation of UAA levels with blood glucose levels and HOMA–IR in patients with T2DM.ConclusionOur study has shown subtle abnormalities in UAA patterns in patients with T2DM. The measurement of UAA levels and excretory pattern can be used as an index of hyperglycemia and IR which could serve as an inexpensive and non-invasive marker for T2DM. More studies are required to confirm this association.