Objective: To evaluate the safety and efficacy of metformin in patients with type 2 diabetes mellitus (T2DM) and chronic hepatitis C virus (HCV) with or without cirrhosis and hepatocellular carcinoma (HCC). Data Sources: A PubMed (1946-August 2013) search using the keywords type 2 diabetes mellitus, metformin, hepatitis C virus, cirrhosis, and hepatocellular carcinoma was conducted. The references in published articles were reviewed to identify additional references for inclusion. Study Selection and Data Extraction: Studies written in English, evaluating metformin use in human patients with T2DM and chronic HCV were included. Data Synthesis: Eight studies met criteria for inclusion. Two prospective, randomized controlled trials showed increased benefit with metformin on virological response in patients with insulin resistance receiving HCV treatment. A prospective observational study evaluated metformin exclusively in patients with T2DM and HCV and showed significant reductions in the occurrence of HCC, liver-related death, and liver transplant. Four retrospective case control studies showed a decreased risk of HCC with metformin treatment in patients with T2DM and chronic liver disease. Finally, a retrospective cohort study indicated an increased survival rate in patients with diabetes and HCC undergoing radiofrequency ablation. Although diarrhea was increased in patients receiving metformin, no serious adverse effects, including lactic acidosis, were reported. Conclusions: Metformin may provide benefit in the treatment of HCV and in reducing the risk of HCC in patients with T2DM and HCV. Further long-term, randomized controlled trials are needed to adequately assess the safety and efficacy of metformin therapy in patients with comorbid diabetes and chronic HCV.
Brief Reports.These are either preliminary original research reports of studies that have a high potential for significant clinical impact or hybrid reports embracing a small case series with a clear research question posed and answered.
Abstract: Type 1 diabetes mellitus (T1DM) is characterized by relative or absolute insulin deficiency. Despite treatment with insulin therapy, glycemic goals are not always met, and insulin therapy is sometimes limited by adverse effects, including hypoglycemia and weight gain. Several adjunctive therapies have been evaluated in combination with insulin in patients with T1DM to improve glycemic control while minimizing adverse effects. Pramlintide, an amylin analog, can improve glycemic control, primarily through lowering postprandial blood glucose levels. Patients may experience weight loss and an increased risk of hypoglycemia and require additional mealtime injections. Metformin provides an inexpensive, oral treatment option and may reduce blood glucose, especially in overweight or obese patients with minimal risk of hypoglycemia. Metformin may be more effective in patients with impaired insulin sensitivity. Glucagon-like peptide-1 receptor agonists reduce primarily postprandial blood glucose and insulin dose and promote weight loss. They are expensive, cause transient nausea, may increase risk of hypoglycemia and require additional injections. Sodium–glucose transport-2 inhibitors improve glycemic control, promote weight loss and have low risk of hypoglycemia with appropriate insulin adjustment; however, these agents may increase the risk of diabetic ketoacidosis in patients with T1DM. Patient-specific characteristics should be considered when selecting adjunctive therapy for patients with T1DM. Close monitoring, insulin dose adjustments and patient education are all important to ensure safe and effective use of these agents. Keywords: type 1 diabetes mellitus, metformin, amylin, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, dipeptidyl-peptidase 4 inhibitors
Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of the fixed-dose combination of insulin degludec and the glucagon-like peptide-I receptor agonist (GLP-1 RA), liraglutide (IDegLira) in the treatment of type 2 diabetes mellitus (T2DM). Data Sources: A PubMed and MEDLINE search (1966 to July 2017) of the keywords insulin degludec, liraglutide, and type 2 diabetes mellitus was conducted. References were reviewed to identify additional citations. Study Selection and Data Extraction: Articles written in English were included if they evaluated the pharmacokinetics, pharmacology, clinical efficacy, or safety of IDegLira in humans. Data Synthesis: IDegLira displayed pharmacokinetic and pharmacodynamic properties similar to that of the individual components. IDegLira has shown significant hemoglobin A1C (A1C) reductions of 1.3% to 1.9% and fasting plasma glucose reductions of 45 to 65 mg/dL when used in patients with T2DM previously receiving oral antihyperglycemic agents (AHAs), GLP-1 RAs, or basal insulin. Weight loss also occurred when IDegLira was started in patients previously receiving oral AHAs or basal insulin. Adverse effects (AEs) tended to be mild and transient. The most common AEs were headache, nasopharyngitis, upper-respiratory infections, and gastrointestinal disorders. Hypoglycemia risk was lower with IDegLira than basal insulin alone but higher than liraglutide alone. Conclusions: IDegLira may provide additional glycemic control with fewer AEs for patients uncontrolled on a GLP-RA or basal insulin alone. Additional studies evaluating use in patients on oral AHAs with higher A1C values and in comparison to bolus insulin are needed.
Brief Reports.These are either preliminary original research reports of studies that have a high potential for significant clinical impact or hybrid reports embracing a small case series with a clear research question posed and answered.
OBJECTIVE: To review pharmacologic, pharmacokinetic, efficacy, and safety data of once-weekly glucagon-like peptide-1 (GLP-1) agonists exenatide long-acting release (LAR), albiglutide, and taspoglutide in treatment of type 2 diabetes mellitus (T2DM). DATA SOURCES: A MEDLINE search (1966-August 2011) was conducted using the following key words: type 2 diabetes mellitus, glucagon-like peptide-1 agonists once weekly, glucagon-like peptide-1 agonists, exenatide LAR, albiglutide, and taspoglutide. STUDY SELECTION AND DATA EXTRACTION: All articles published in English identified from the data sources were evaluated, prioritizing randomized controlled trials with human data. The references of published articles identified were examined for additional studies appropriate for the review. DATA SYNTHESIS: Native GLP-1 increases glucose-dependent insulin secretion, decreases glucagon secretion, and slows gastric emptying in healthy individuals, but these effects may be blunted in patients with T2DM. Because native GLP-1 is rapidly degraded by dipeptidyl peptidase-IV, it is not a practical treatment option. Currently, 2 GLP-1 receptor agonists have been approved by the Food and Drug Administration: exenatide twice daily and liraglutide once daily. Several additional GLP-1 agonists, including exenatide LAR, albiglutide, and taspoglutide, are in various stages of clinical trials and have been modified to increase their half-lives. These agents have shown significant improvements in hemoglobin A 1c , fasting plasma glucose, and postprandial plasma glucose, as well as improvements in body weight, blood pressure, and lipid parameters. These agents allow for less-frequent dosing schedules, improved glycemic control throughout the day, and improved treatment satisfaction compared to some available agents. GLP-1 agonists have been well tolerated, with the most common adverse effects being gastrointestinal related, which occurred early in therapy but typically resolved after 4-8 weeks. The incidence of hypoglycemia was infrequent and mild during therapy. CONCLUSIONS: Once-weekly GLP-1 agonists provide similar glycemic control with weight reduction, as well as overall higher treatment satisfaction for patients because of their ease of use and need for less-frequent dosing compared to some available agents.
