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OBJECTIVE To comprehensively evaluate four weekly preparations of glucagon-like peptide-1 receptor agonist （GLP-1RA） marketed in China，and to provide evidence for hospitals to optimize drug catalogs and clinical rational drug use. METHODS Mini health technology assessment method was used to establish detailed evaluation rules according to A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions， and conduct comprehensive evaluation of four GLP- 1RA weekly preparations from aspects of pharmaceutical characteristics， effectiveness， safety， economy and other attributes. RESULTS Mini health technology assessment scores of the four GLP-1RA weekly preparations from high to low were dulaglutide 78.60 points， semaglutide 77.35 points，polyethylene glycol loxenatide 67.40 points， and exenatide microspheres 65.50 points， respectively. Dulaglutide had advantages in reducing blood sugar， arteriosclerotic cardiovascular disease， kidney benefits， and cost- effectiveness. Semaglutide had advantages in reducing blood sugar and weight loss， but its cost-effectiveness was lower than that of dulaglutide. Exenatide microspheres had advantages in the use of children， but its daily average treatment cost is the highest. Polyethylene glycol loxenatide needed further clinical evidence. CONCLUSIONS Four GLP-1RA weekly preparations all have high pharmaceutical comprehensive scores. Dulaglutide and semaglutide may have more comprehensive pharmaceutical value among them， while the use of exenatide microspheres for children is unique.
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Objective:To investigate the effect of voglibose combined with exenatide on blood glucose control and serum fibroblast growth factor 21 (FGF-21) expression in patients with type 2 diabetes mellitus (T2DM).Methods:Three hundred and eighty patients with T2DM admitted to Qingdao Municipal Hospital from October 2018 to September 2020 were selected and randomly divided into the control group and the observation group, with 190 patients in each group. The control group was treated with voglibose, and the observation group was treated with voglibose and exenatide. Both groups were treated for 16 weeks. Blood glucose, blood fat, insulin and other indicators as well as serum FGF-21 levels were compared between the two groups before and after the treatment, and the efficacy of drugs and the incidence of adverse reactions were compared.Results:The total effective rate in the observation group was higher than that in the control group: 97.89%(186/190) vs. 93.16%(177/190), χ2 = 5.00, P<0.05. After treatment, the levels of fasting plasma glucose (FPG), 2 h plasma glucose (2 h PG) and glycosylated hemoglobin (HbA 1c) in the observation group were lower than those in the control group: (6.95 ± 1.03) mmol/L vs. (8.29 ± 1.15) mmol/L, (7.88 ± 2.07) mmol/L vs. (10.03 ± 3.24) mmol/L, (7.17 ± 1.08)% vs. (8.13 ± 1.21)%, P<0.05. After treatment, the levels of triacylglycerol (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the observation group were lower than those in the control group: (2.13 ± 0.23) mmol/L vs. (2.93 ± 0.34) mmol/L, (3.10 ± 1.01) mmol/L vs. (3.98 ± 1.14) mmol/L, (1.93±0.38) mmol/L vs. (2.73±0.54) mmol/L, P<0.05. After treatment, the level of islet β cell function index (HOMA-β) in the observation group was higher than that in the control group: 111.56 ± 20.78 vs. 102.23 ± 20.14, P<0.05. After treatment, the level of serum FGF-21 in the observation group was lower than that in the control group: (142.09 ± 26.82) ng/L vs. (150.22 ± 30.21) ng/L, P<0.05. The incidence of adverse reactions between the two groups had no significant difference ( P>0.05). Conclusions:Voglibose combined with exenatide has a definite effect on T2DM patients with metformin failure, which can effectively control their blood glucose level, reduce serum FGF-21 level, improve insulin resistance and glucose and lipid metabolism, and reduce body mass, with high safety.
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AIM: To explore which variables can predict the weight response to exenatide and to individualize specific therapies for patients with type 2 diabetes mellitus (T2DM) who need treatment with exenatide. METHODS: We performed a study among T2DM patients who were treated with exenatide twice daily for at least 12 months from January 2017 to December 2020. Data of the height, weight, body mass index (BMI) calculated, and HbA1c, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting serum insulin (FINS), postprandial serum insulin (PINS), blood lipids and concurrent diabetic medications at baseline, 3 months, 6 months and 12 months after exenatide initiation were collected. Patients were categorized into two cohorts based on weight loss ≥3%: responders and non-responders. The binary logistic regression analysis was used to identify the major variables of weight response to exenatide. RESULTS: The duration of diabetes in the responder group was shorter than that in patients in the non-responder group (P<0.05). For patients in the responder and non-responder groups, there was a significant decrease in weight, BMI, HbA1c, FPG, PPG, homeostasis model assessment of insulin resistance (HOMA-IR) and increase in homeostasis model assessment for beta cell function (HOMA-B) compared with the prarameters before treatment with exenatide (P<0.001). The baseline weight and baseline HbA1c were associated with weight loss after 6 months of treatment with exenatide (P<0.05). CONCLUSION: Baseline weight and HbA1c improvement were positively correlated with weight loss after 6 months of treatment with exenatide and the major predictors of weight response to exenatide.
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Diabetes mellitus is a major health problem with increasing prevalence at a global level. The discovery of insulin in the early 1900s represented a major breakthrough in diabetes management, with further milestones being subsequently achieved with the identification of glucagon-like peptide-1 (GLP-1) and the introduction of GLP-1 receptor agonists (GLP-1 RAs) in clinical practice. Moreover, the subcutaneous delivery of biotherapeutics is a well-established route of administration generally preferred over the intravenous route due to better patient compliance and prolonged drug absorption. However, current subcutaneous formulations of GLP-1 RAs present pharmacokinetic problems that lead to adverse reactions and treatment discontinuation. In this review, we discuss the current challenges of subcutaneous administration of peptide-based therapeutics and provide an overview of the formulations available for the different routes of administration with improved bioavailability and reduced frequency of administration.
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Exenatide is the first approved glucagon-like peptide 1 receptor agonist subcutaneously or intramus-cularly injected for the treatment of type 2 diabetes mellitus. Typical therapeutic plasma concentrations are in the low pg/mL range, therefore requiring ultra-sensitive quantification. To enable the accurate evaluation of pharmacokinetic studies, we established a UPLC-MS/MS assay with a lower limit of quantification (LLOQ) of 5 pg/mL (1.2 pM) using 200μL of plasma, validated according to FDA''s and EMA''s pertinent guidelines. Exenatide was isolated from plasma with solid phase extraction utilizing anion-exchange sorbent. Quantification was performed with positive electrospray ionization tandem mass spectrometry in the selected reaction monitoring mode. The calibrated concentration range of 5-10,000 pg/mL was linear showing correlation coefficients>0.99. Interday and intraday accuracy ranged from 97.5％to 105.4％with corresponding precision of<10.9％. Accuracy at the LLOQ ranged from 93.0％to 102.5％with corresponding precision of<15.9％. Because of the validity of a 10-fold dilution QC (accuracy 111.2％), the assay is suitable for exenatide quantification up to 100,000 pg/mL. The ultra-sensitive assay''s applicability was demonstrated by the quantification of exenatide plasma concentrations and pharma-cokinetics after intravenous and nasal administration to beagle dogs.
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The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ingredients require appropriate administration, without the development of adverse effects or toxicity. Therefore, it is required to develop several quantification methods for GLP-1 analogs products, in order to achieve the therapeutic goals, among which ELISA and HPLC arise. These methods are developed, optimized and validated in order to determine GLP-1 analogs, not only in final formu-lation of the active pharmaceutical ingredient, but also during preclinical and clinical trials assessment. This review highlights the role of ELISA and HPLC methods that have been used during the assessment for GLP-1 analogs, especially for exenatide.
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Objective: To investigate the protective effect of exenatide on patients with diabetic kidney disease in early stage and its mechanism. Methods: From January 2015 to August 2018, a total of 80 patients with diabetic kidney disease in early stage in The First Affiliated Hospital of Soochow University were randomly divided into observation group and control group with 40 in each. Patients in control group were treated with olmesartan and metformin orally. Those in observation group were treated with exenatide subcutaneously on the basis of the same treatment in control group. Blood glucose, blood lipid, renal function, serum advanced glycosylation end products (AGEs), cyclic adenosine phosphate (cAMP), serum oxidative stress and peripheral blood mononuclear cells (PBMC) were compared before and after treatment. Results: After 24 weeks of treatment, the levels of FBG, HbAlc, MBG, SDBG, BGFR and MAG were significantly lower in observation group than in control group (P0.05). However, the systolic and diastolic blood pressure in control group was significantly decreased after treatment (P0.05). Conclusion: Exenatide has a certain protective effect on diabetic kidney disease in early stage. It may be related to decreasing AGEs production, improving oxidative stress and regulating cAMP/PKA signaling pathway.
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Abstract Purpose: To investigate the effects of exenatide on renal injury in streptozotocin-induced diabetic rats. Methods: Fifty SD rats were randomly divided into normal control, model, exenatide-1, exenatide-2 and exenatide-3 groups, 10 rats in each group. The diabetic nephropathy model was constructed in later 4 groups. Then, the later 3 groups were treated with 2, 4 and 8 μg/kg exenatide for 8 weeks, respectively. The serum and urine biochemical indexes and oxidative stress and inflammatory indexes in renal tissue were determined. Results: Compared to the model group, in exenatide-3 group the serum fasting plasma glucose and hemoglobin A1c levels were significantly decreased, the fasting insulin level was significantly increased, the renal index and blood urea nitrogen, serum creatinine and 24 h urine protein levels were significantly decreased, the renal tissue superoxide dismutase and glutathione peroxidase levels were significantly increased, the malondialdehyde level was significantly decreased, and the renal tissue tumor necrosis factor alpha, interleukin 6, hypersensitive C-reactive protein and chemokine (C-C motif) ligand 5 levels were significantly decreased P<0.05). Conclusions: Exenatide can mitigate the renal injury in diabetic rats. The mechanisms may be related to its resistance of oxidative stress and inflammatory response in renal tissue.
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Animals , Male , Rats , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , Exenatide/therapeutic use , Random Allocation , Rats, Sprague-Dawley , Oxidative Stress , Diabetes Mellitus, Experimental/physiopathology , Diabetic Nephropathies/prevention & control , Disease Models, Animal , Kidney/drug effectsABSTRACT
Objective To observe the clinical effect of exenatide for treatment of obesity type 2 diabetes mellitus (T2DM) conplicated with obstructive sleep apnea hypopnea syndrome(OSAHS).Methods Eighty patients of obesity T2DM complicated with OSAHS in the Department of Endocrinology,the First People's Hospital of Xinxiang from August 2014 to August 2016 were chosen and randomly divided into observation group(n =40) and control group(n =40).The patients in control group taken orally mefformin 800 mg twice daily for 24 weeks;based on this,the patients in observation group were injected subcutaneously exenatide 10 μg at one hour before meal,twice daily for 24 weeks.The fasting blood glucose (FBG),2-hour postprandial blood glucose (2 hPBG),glycosylated hemoglobin (HbA1 C),body mass index (BMI),waistline,total cholesterol (TC),triglyceride (TG),apnea hypoventilation index (AHI),Epworth sleepiness scale (ESS) score,the lowest oxygen saturation in sleep (LSpO2) were compared between the two groups before and after treatment.Results There was no statistic difference in the HbA1 C,FPG,2 hPBG levels of patients between the two groups before treatment (P ＞ 0.05);the HbA1 C,FPG,2 hPBG levels of patients in the two groups after treatment were significantly lower than those before treatment (P ＜ 0.05);and the HbA1 C,FPG,2 hPBG levels of patients in observation group were significantly lower than those in the control group after treatment(P ＜ 0.05).There was no statistic difference in the BMI,waistline and TC,TG levels of patients between the two groups before treatment(P ＞ 0.05);the BMI,waistline and TC,TG levels of patients in the two groups after treatment were significantly lower than those before treatment (P ＜ 0.05);and the BMI,waistline and TC,TG levels of patients in observation group were significantly lower than those in the control group after treatment(P ＜ 0.05).There was no statistic difference in the AHI,ESS scores,SpO2 and LSpO2 levels of patients between the two groups before treatment(P ＞0.05);the AHI,ESS scores,SpO2 and LSpO2 levels of patients in the two groups after treatment were significantly lower than those before treatment(P ＜0.05);and the AHI,ESS scores,SpO2 and LSPO2 levels of patients in observation group were significantly lower than those in the control group after treatment(P ＜0.05).The incidence of adverse reaction of patients in observation group and control group was 7.5％ (3/40) and 5.0％ (2/40) respectively;there was no statistic difference in the incidence of adverse reaction between the two groups (P ＞ 0.05).Conclusion Exenatide can effectively control blood glucose,improve the function of beta cells and reduce insulin resistance.It can effectively reduce body weight,BMI and waistline,improve the quality of sleep breathing.
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Objective: To investigate the effect of exenatide on body weight, blood glucose, blood lipids, insulin resistance and the degree of fatty liver in young and middle-aged patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Meth-ods: Totally 70 young and middle-aged patients with poorly controlled type 2 diabetes and NAFLD were chosen and randomly divided into observation group and the control group with 35 cases in each group. The patients were treated with exenatide or isophane prota-mine biosynthetic human insulin injection for 3 months on the basis of original oral hypoglycemic drugs. The body weight, BMI, waist circumference, HOMA-IR, plasma glucose (FPG), 2 hour postprandial blood glucose (2hPG), glycated hemoglobin (HbAlc), blood lipids, liver function indices (ALT, AST and GGT), and the severity of fatty liver were compared before and after the treatment. Re-sults: After the 3-month treatment, there was no significant difference in glycemic control between observation group and the control group. After treatment, the body weight, BMI, waist circumference, HOMA-IR, TG, ALT, AST and GGT in observation were signifi-cantly decreased than those before the treatment(P<0. 05), and were superion to those in control group(P<0. 05). While in the control group, all the above indices were not significantly changed before and after the treatment (P>0. 05). The total efficiency for treating NAFLD in observation group was significantly higher than that in the control group (P<0. 05). Conclusion: Besides reducing blood glucose effectively, exenatide can also obviously reduce body weight and TG level, improve insulin resistance, decrease liver en-zymes, and significantly ameliorate the degree of fatty liver. The results suggested that exenatide might be a new therapeutic option for young and middle-aged patients with type 2 diabetes and NAFLD.
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OBJECTIVE: Blood tends to deposit in atrium to form thrombus in patients with atrial fibrillation. Patients with diabetes are in high coagulation state, for whom thrombosis is easy to occur. The number of diabetic patients with atrial fibrillation is large. Warfarin is one of the most widely used oral anticoagulants, which can cause major or fatal bleeding, so it is necessary to perform regular monitoring of international normalized ratio (INR) on all patients treated with warfarin. New kinds of antidiabetic drugs are widely used in clinic, among which a lot affect INR levels achieved with warfarin therapy. Clinical pharmacists should pay attention to drug interactions and monitor adverse drug reactions. As a new antidiabetic drug, exenatide has less reports of interaction with warfarin. The characteristic of the interaction between exenatide and warfarin was investigated, with the aim to optimize the rational and individualized medication. METHODS: A case was introduced in which exenatide was administrated combined with warfarin, so that the possible mechanism of exenatide affecting to warfarin were analyzed. RESULTS: INR declined from 2.13 to 1.57 after exenatide being added, and decreased further to 1.43 with concurrency of the increasing exenatide dose. On the contrary, INR was on rise as result of discontinuing exenatide. At last, INR returned to 1.78 when the patient discharged. CONCLUSION: Exenatide inhibited the absorption of warfarin, which lead to INR decline attributed to its effect of slowing down the gastric emptying. When exenatide and warfarin are combined, the dose of warfarin must be adjusted based on INR under clinical monitoring.
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Objective Meta-analysis the efficacy and safety of Exenatide and insulin therapy oral hypoglycemic drugs effect of obesity with type 2 diabetes .Methods According to the research purpose to set up the screening of related literature and exclusion criteria; formulatethe searching strategy, through PubMed、the Chinese Biological Medicine Datebase(CBM)、 CNKI、Wanfang Data Knowledge Service Platform, VIP to retrieve all theliterature selection of efficacy and safety by Exenatide oral hypoglycemic drugs and insulin therapy of obese type 2 diabetes mellitus.Choose met inclusion exclusion criteria, the complete data information randomized controlled trial (RCT) as the research object; Apply to the international commonly used Jadad score method to evaluate quality included in the test; To process the relevant data in the test ; Apply the ReviewManager 5.1 software to analysis the extracted research data.Analysis the results and put forward conclusions.Results Participants included 11 RCT , meta analysis results showed that compared with the Exenatide, in terms of reducing fasting glucose ,insulin effect more apparent [MD = 0.35, 95％CI: (0.11, 0.59), P = 0.004)]. In control effect of glycosylated hemoglobin, there was no statistically significant difference[MD=-0.04 ,95％CI:(-0.20,0.11), P=0.58],between Exenatide and insulin. Compared with the insulin, Exenatide reduce BMI more apparent[MD=-2.77,(95％CI: -3.34,-2.20),P<0.00001]; Compared with the insulin, Exenatide reduce insulin resistance index, the effect is more obvious[MD=-1.67,95％CI:(-1.93,-1.41), P<0.00001]; Adverse reaction in the process of treatment, the insulin is more likely to lead to hypoglycemia, [OR = 0.32, 95％ CI: 0.19, 0.54), P<0.0001]; While Exenatide are more likely to lead to gastrointestinal adverse reaction [OR = 4.04, 95％ CI: 2.35, 6.93), P<0.00001).Conclusion According to the Meta-analysis: Exenatide can be used in the treatment of oral hypoglycemic drugs of adult obesity with type 2 diabetes, and obvious effects of treatment of insulin resistance, long-term results still needs a large number of samples of high quality RCT to verify.
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Objective To observe the effect of exenatide on endoplasmic reticulum stress (ERS) in human renal mesangial cells (HRMCs) injured by fluctuating hyperglycemia culture,and to explore the mechanism.Methods HRMCs were randomly divided into three groups:control group (group N,cells were cultured in 5.6 mmol/L glucose for 24 h),fluctuating hyperglycemia group (group F,cells were cultured in 30 mmol/L glucose for 3 h,5.6 mmol/L glucose for 2 h,repeated three times in one day,then 5.6 mmoll/L glucose overnight),fluctuating hyperglycemia and exenatide group (group F+G,HRMCs were cultured in fluctuating hyperglycemia and 100 nmol/L exenatide).MTT assay was used to measure the viability in each group.The apoptosis rates were detected by flow cytometry in three groups.The relative expression of glucose regulated protein78 (GRP78) and CCAAT/enhancerbinding protein homologous protein (CHOP) were tested by Western blot assay.Results Compared with the group N,the cell proliferation level decreased,the cell apoptosis rate increased,and the expression levels of GRP78 and CHOP increased in F group (P ＜ 0.05).After treatment with exenatide,the cell proliferation rate increased,cell apoptosis rate decreased (P ＜ 0.05),and the expression levels of GRP78 and CHOP decreased in F+G group,compared with those of the group F (P ＜ 0.05).Conclusion Exenatide can reduce the damage of fluctuating hyperglycemia on HRMCs by down-regulating the stress levels of the endoplasmic reticulum stress.
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Objective: To investigate the effects of exenatide on body weight, blood glucose, blood lipids and proteinuria in obese and overweight young and middle-aged patients with type 2 diabetes to provide reference for better controlling the macro-vascular and micro-vascular complications in the patients.Methods: Totally 60 obese and overweight young and middle-aged patients with poorly controlled type 2 diabetes were chosen and randomly divided into exenatide group and novolin N group with 30 ones in each.The patients maintained the previous oral hypoglycemic drugs, and exenatide group was treated with exenatide, Novolin N group was treated with protamine biosynthetie human insulin(NovolinN), and the treatment course was 3 months.The body weight, BMI, fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPG), glycated hemoglobin (HbA1C), fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP), blood lipids, plasma homocysteine (HCY) and urine microalbumin (UMA) were compared before and after the treatment.Results: After 3 month treatment,the FPG,zhpG and HbAlc were significantly decreased both in exenatide group and NwoCinN group(P0.05).In exenatide group, the levels of FCP and 2hCP were higher than those before the treatment (P0.05).Conclusion: Exenatide can effectively control blood glucose, improve β-cell function, reduce body weight, lower blood lipids and decrease urine protein.
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[Objective] To investigate the role of exenatide on angiogenesis in endometrial cancer Ishikawa xenografts in nude mice.[Method] We used the subcutaneous human endometrial cancer cell Ishikawa xenografts in nude mice model,and divided them into control group and exenatide-treated group.The harvested tumors were preserved for immunohistochemistry staining and western blot analysis.[Results] The micro-vessel density (CD31 positive) in exenatide-treated group was (13.2 ± 1.4)/400 power field,less than that in control group [(25.9 ± 5.8)/400 power field] (P ＜ 0.01).The expression level of VEGF was significantly lower in exenatide-treated group than that in control group (P ＜ 0.05).The mean density of tumor associated macrophages (F4/80 positive) is (31.4 ± 3.4)％ in exenatide-treated group and (72.1 ± 4.2)％ in control group with significant difference (P ＜ 0.01).[Conclusion] Exenatide weaks tumor angiogenesis within endometrial cancer Ishikawa xenografts in nude mice.
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Objective To investigate the efficacy and safety of domestic exenatide injection versus imported exenatide injection in type 2 diabetic patients with inadequate glycemic control on monotherapy or combination therapy of metformin and insulin secretagogues. Methods A multicenter, randomized, parallel-controlled, and non-inferiority trial was carried out. A total of 240 subjects were randomized at a 1:1 ratio to add domestic exenatide injection (trial group) or imported exenatide injection (control group) on the background therapies. The primary endpoint of efficacy was HbA1C change from baseline to week 16. The secondary endpoints of efficacy were the proportion of HbA1C0.05). The changes in FPG, 2hPG, 7P-SMBG and body weight from baseline to week 16 were comparable between the two groups (all P>0.05). Moreover, the incidences of hypoglycemia and adverse events were similar between the two groups (both P>0.05). Conclusion In type 2 diabetic patients inadequately controlled by monotherapy or combination therapy of metformin and insulin secretagogues, the efficacy of cotreatment with domestic exenatide injection is not inferior to that of imported product ones, with a similar safety profile.
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Objective To observe the therapeutic effect of exenatide combined with metformin therapy in type 2 diabetes with nonalcoholic fatty liver disease.Methods 50 patients with type 2 diabetes and nonalcoholic fatty liver disease were randomly divided into experimental group and control group with 25 cases in each.The control group were treated with metformin, the experimental group were treated with exenatide on the basis of metformin.Before treatment and at the end of 12-week treatment, patients height, weight, body mass index(BMI), waistline(WC), glycated hemoglobin(HbA1c), fasting blood glucose(FBG),fasting C-peptide(FCP), triglyceride(TG), cholesterol(TCH), high density lipoprotein(HDL), low density lipoprotein(LDL),systolic pressure(SBP), diastolic pressure(DBP), alanine aminotransferase(ALT), superoxide dismutase(SOD), liver lipid contents(LFC) were detected.Results Baseline data were not significantly different between the two groups.Compared to baseline, WC, HbA1c, FBG and LFC in experimental group and control group were obviously improved after treatment(P<0.05), and the experimental group improved more significantly than control group(P<0.05).Conclusion Exenatide combined with metformin has an obvious therapeutic effect on BMI, WC, HbA1c, FBG, FCP, SBP, TG, TCH, HDL, LDL, LFC than mere metformin treatment in treatment of type 2 diabetes with nonalcoholic fatty liver disease.
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OBJECTIVE:To observe clinical efficacy and safety of exenatide combined with clomiphene citrate in the treatment of polycystic ovary syndrome with insulin resistance. METHODS:98 patients with polycystic ovary syndrome complicated with in-sulin resistance were randomly divided into control group (49 cases) and observation group (49 cases). Control group was given Clomiphene citrate capsule 50 mg orally,once a day,for 5 d+Metformin enteric-coated tablet with initial dose of 0.25 g orally, twice a day,adjusted to 0.50-0.75 g orally,twice a day,for 3 menstrual cycles. Observation group was given Clomiphene citrate capsule(usage and dosage same as control group)+Exenatide injection 5 μg subcutaneously,twice a day,adjusted to 10 μg subcu-taneously,twice a day,for 2 months. Clinical efficacies of 2 groups were observed as well as the levels of LH,FSH,LH/FSH and IR before and after treatment,ovulation and pregnancy of infertility patients after treatment. The occurrence of ADR was record-ed. RESULTS:Total response rate,ovulation rate and pregnancy rate of observation group were significantly higher than that of con-trol group,with statistical significance(P0.05). After treatment,the levels of LH,LH/FSH and IR in 2 groups were significantly lower than before,and the observation group was significantly lower than the control group,the levels of FSH in 2 groups was sig-nificantly higher than before,and the observation group was significantly higher than the control group,with statistical significance (P0.05). CONCUSIONS:Exenatide com-bined with clomiphene citrate shows significant therapeutic efficacy for polycystic ovary syndrome complicated with insulin resis-tance and can increase ovulation rate and pregnancy rate through improving insulin resistance,but doesn't increase the occurrence of ADR.
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BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing in Korea. Clinical studies in patients with T2DM have shown that combining the glucagon-like peptide-1 receptor agonist exenatide twice daily with basal insulin is an effective glucose-lowering strategy. However, these studies were predominantly conducted in non-Asian populations. METHODS: We conducted a subgroup analysis of data from a multinational, 30-week, randomized, open-label trial to compare the effects of exenatide twice daily (n=10) or three times daily mealtime insulin lispro (n=13) among Korean patients with T2DM inadequately controlled (glycosylated hemoglobin [HbA1c] >7.0%) on metformin plus optimized insulin glargine. RESULTS: Exenatide twice daily and insulin lispro both reduced HbA1c (mean −1.5% and −1.0%, respectively; P<0.01 vs. baseline). Fasting glucose and weight numerically decreased with exenatide twice daily (−0.7 mmol/L and −0.7 kg, respectively) and numerically increased with insulin lispro (0.9 mmol/L and 1.0 kg, respectively). Minor hypoglycemia occurred in four patients receiving exenatide twice daily and three patients receiving insulin lispro. Gastrointestinal adverse events were the most common with exenatide twice daily treatment. CONCLUSION: This analysis found treatment with exenatide twice daily improved glycemic control without weight gain in Korean patients with T2DM unable to achieve glycemic control on metformin plus basal insulin.
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Humans , Diabetes Mellitus, Type 2 , Fasting , Glucagon-Like Peptide-1 Receptor , Glucose , Hypoglycemia , Insulin Glargine , Insulin Lispro , Insulin , Korea , Meals , Metformin , Obesity , Prevalence , Weight GainABSTRACT
OBJECTIVE: To develop an easy to scale-up preparation process for exenatide-loaded long-acting microspheres, and develop a method that can be used to rapidly evaluate the in vitro release properties of the microspheres. METHODS: The primary emulsion could be made by high shear emulsification process combined with high pressure homogenization method, then exenatide-loaded microspheres were prepared by a modified coacervation method. In the coacervation step, static mixer was used for mixing the primary emulsion and the coacervation reagent. RESULTS: High pressure homogenization could reduce the size of the primary emulsion to about 200 nm. The encapsulation efficiency of microspheres was greater than 96.8%, and the amount of burst release in 1 h was less than 0.5%. When the scale of microspheres preparation was magnified by five times, the characteristics of the obtained microspheres was the same as the small scale batch. The in vitro release curves showed that the continued release time lasted for nearly 4 weeks after the 17 d lag phase. The drug release rate at 45℃ was as high as 2.5 times of that at 37℃, with same release curves. CONCLUSION: The established preparation process of exenatide-loaded long-acting microspheres, which uses static mixer for mixing the primary emulsion and coacervation reagent, is easy for scaling-up and industrialization. Accelerated test at 45℃ can be used to rapidly evaluate the in vitro release profile of the microspheres.