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      Exenatide once-weekly injection for the treatment of type 2 diabetes in Chinese patients: current perspectives

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          Abstract

          Glucagon-like peptide-1 (GLP-1) analogs, such as exenatide, have played an important role as antidiabetic medications in the treatment of type 2 diabetes (T2DM). Like most other hypoglycemic agents, exenatide has a number of actions, including lowering blood glucose, promoting weight loss, improving insulin resistance, and protecting islet β-cells. Although GLP-1 analogs, combined with other antidiabetic medications, have excellent performance in T2DM, some side effects and imperfections limit its use in clinical practice. Since 2012, a new generation GLP-1 agent, exenatide once weekly (QW), has been available for patients with T2DM in the USA, but not as yet in the People’s Republic of China. Previous data indicate that exenatide QW achieves better fasting glucose reductions than sitagliptin or exenatide twice daily, whilst appearing non-inferior to pioglitazone and achieving less reductions than insulin glargine. Exenatide QW was better at improving average postprandial glucose than sitagliptin or titrated insulin glargine, but was inferior to exenatide twice daily. Additionally exenatide QW has a better effect in terms of weight loss than other glycemic medications. Exenatide QW can also reduce blood lipids and lower blood pressure. Accordingly, exenatide QW is cost-effective, achieves good clinical outcomes, and has acceptable side effects, indicating that it has promising prospects for future use in the People’s Republic of China.

          Most cited references65

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          The biology of incretin hormones.

          Gut peptides, exemplified by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted in a nutrient-dependent manner and stimulate glucose-dependent insulin secretion. Both GIP and GLP-1 also promote beta cell proliferation and inhibit apoptosis, leading to expansion of beta cell mass. GLP-1, but not GIP, controls glycemia via additional actions on glucose sensors, inhibition of gastric emptying, food intake and glucagon secretion. Furthermore, GLP-1, unlike GIP, potently stimulates insulin secretion and reduces blood glucose in human subjects with type 2 diabetes. This article summarizes current concepts of incretin action and highlights the potential therapeutic utility of GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of type 2 diabetes.
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            Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes

            OBJECTIVE—The efficacy and safety of adding liraglutide (a glucagon-like peptide-1 receptor agonist) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes (OAD) therapy. RESEARCH DESIGN AND METHODS—In this 26-week, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial, 1,091 subjects were randomly assigned (2:2:2:1:2) to once-daily liraglutide (either 0.6, 1.2, or 1.8 mg/day injected subcutaneously), to placebo, or to glimepiride (4 mg once daily). All treatments were in combination therapy with metformin (1g twice daily). Enrolled subjects (aged 25–79 years) had type 2 diabetes, A1C of 7–11% (previous OAD monotherapy for ≥3 months) or 7–10% (previous OAD combination therapy for ≥3 months), and BMI ≤40 kg/m2. RESULTS—A1C values were significantly reduced in all liraglutide groups versus the placebo group (P < 0.0001) with mean decreases of 1.0% for 1.8 mg liraglutide, 1.2 mg liraglutide, and glimepiride and 0.7% for 0.6 mg liraglutide and an increase of 0.1% for placebo. Body weight decreased in all liraglutide groups (1.8–2.8 kg) compared with an increase in the glimepiride group (1.0 kg; P < 0.0001). The incidence of minor hypoglycemia with liraglutide (∼3%) was comparable to that with placebo but less than that with glimepiride (17%; P < 0.001). Nausea was reported by 11–19% of the liraglutide-treated subjects versus 3–4% in the placebo and glimepiride groups. The incidence of nausea declined over time. CONCLUSIONS—In subjects with type 2 diabetes, once-daily liraglutide induced similar glycemic control, reduced body weight, and lowered the occurrence of hypoglycemia compared with glimepiride, when both had background therapy of metformin.
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              Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study.

              Glucagon-like peptide 1 (GLP-1) has been proposed as a treatment for type 2 diabetes. We have investigated the long-term effects of continuous administration of this peptide hormone in a 6-week pilot study. 20 patients with type 2 diabetes were alternately assigned continuous subcutaneous infusion of GLP-1 (n=10) or saline (n=10) for 6 weeks. Before (week 0) and at weeks 1 and 6, they underwent beta-cell function tests (hyperglycaemic clamps), 8 h profiles of plasma glucose, insulin, C-peptide, glucagon, and free fatty acids, and appetite and side-effect ratings on 100 mm visual analogue scales; at weeks 0 and 6 they also underwent dexascanning, measurement of insulin sensitivity (hyperinsulinaemic euglycaemic clamps), haemoglobin A(1c), and fructosamine. The primary endpoints were haemoglobin A(1c) concentration, 8-h profile of glucose concentration in plasma, and beta-cell function (defined as the first-phase response to glucose and the maximum insulin secretory capacity of the cell). Analyses were per protocol. One patient assigned saline was excluded because no veins were accessible. In the remaining nine patients in that group, no significant changes were observed except an increase in fructosamine concentration (p=0.0004). In the GLP-1 group, fasting and 8 h mean plasma glucose decreased by 4.3 mmol/L and 5.5 mmol/L (p<0.0001). Haemoglobin A(1c) decreased by 1.3% (p=0.003) and fructosamine fell to normal values (p=0.0002). Fasting and 8 h mean concentrations of free fatty acids decreased by 30% and 23% (p=0.0005 and 0.01, respectively). Gastric emptying was inhibited, bodyweight decreased by 1.9 kg, and appetite was reduced. Both insulin sensitivity and beta-cell function improved (p=0.003 and p=0.003, respectively). No important side-effects were seen. GLP-1 could be a new treatment for type 2 diabetes, though further investigation of the long-term effects of GLP-1 is needed.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2015
                10 August 2015
                : 11
                : 1153-1162
                Affiliations
                [1 ]Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China
                [2 ]Department of Endocrinology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China
                Author notes
                Correspondence: Bing Chen, Department of Endocrinology, Southwest Hospital, Third Military Medical University, Gaotanyan Street 29, Shapingba District, Chongqing 400038, People’s Republic of China, Tel +86 23 6875 4138, Email chenbing3@ 123456medmail.com.cn
                Gangyi Yang, Department of Endocrinology, Second Affiliated Hospital, Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, People’s Republic of China, Tel +86 23 6848 6115, Email gangyiyang@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                tcrm-11-1153
                10.2147/TCRM.S81088
                4539087
                26309403
                e6f1f23e-b2f4-4345-bbfa-28bce7cc38ed
                © 2015 Deng et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Medicine
                diabetes,glycemic control,exenatide once weekly
                Medicine
                diabetes, glycemic control, exenatide once weekly

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