Efficacy and safety of once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg as add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10)

AimsSUSTAIN 10 compared the efficacy and safety of the anticipated most frequent semaglutide dose (1.0 mg) with the current most frequently prescribed liraglutide dose in Europe (1.2 mg), reflecting clinical practice.MethodsIn this phase 3b, open-label trial, 577 adults with type 2 diabetes (HbA_1c 7.0–11.0%) on 1–3 oral antidiabetic drugs were randomized 1:1 to subcutaneous once-weekly semaglutide 1.0 mg or subcutaneous once-daily liraglutide 1.2 mg. Primary and confirmatory secondary endpoints were changes in HbA_1c and body weight from baseline to week 30, respectively.ResultsMean HbA_1c (baseline 8.2%) decreased by 1.7% with semaglutide and 1.0% with liraglutide (estimated treatment difference [ETD] –0.69%; 95% confidence interval [CI] -0.82 to -0.56, P < 0.0001). Mean body weight (baseline 96.9 kg) decreased by 5.8 kg with semaglutide and 1.9 kg with liraglutide (ETD -3.83 kg; 95% CI -4.57 to -3.09, P < 0.0001). The proportions of subjects achieving glycaemic targets of < 7.0% and = 6.5%, weight loss of = 5% and = 10%, and a composite endpoint of HbA_1c < 7.0% without severe or blood glucose-confirmed symptomatic hypoglycaemia and no weight gain were greater with semaglutide vs liraglutide (all P < 0.0001). Both treatments had similar safety profiles, except for more frequent gastrointestinal disorders (the most common adverse events [AEs]) and AEs leading to premature treatment discontinuation with semaglutide vs liraglutide (43.9% vs 38.3% and 11.4% vs 6.6%, respectively).ConclusionSemaglutide was superior to liraglutide in reducing HbA_1c and body weight. Safety profiles were generally similar, except for higher rates of gastrointestinal AEs with semaglutide vs liraglutide.     

恩格列净联合吡格列酮治疗2型糖尿病的临床研究

目的 探究恩格列净联合吡格列酮治疗2型糖尿病的临床疗效。方法 选取2018年6月-2019年5月于郑州人民医院接受治疗的2型糖尿病患者98例,随机分为对照组和治疗组,每组各49例。对照组于每日早餐前口服盐酸吡格列酮片,30 mg/次,1次/d。治疗组在对照组治疗基础上口服恩格列净片,10 mg/次,1次/d。两组治疗时间均为3个月。观察两组的临床疗效,比较两组治疗前后血糖相关指标、氧化产物和抗氧化指标的变化情况。结果 治疗后,治疗组总有效率是93.88%明显高于对照组77.55%（P<0.05）。治疗后,两组空腹血糖（FPG）、餐后2 h血糖（2 h PG）、糖化血红蛋白（HbA1c）均出现显著降低（P<0.05）;且治疗组较对照组更低（P<0.05）;治疗后,对照组体质量指数（BMI）略高于治疗前数值,差异无统计学意义;治疗后治疗组BMI显著降低（P<0.05）,且治疗组治疗后BMI显著低于对照组（P<0.05）。治疗后,两组超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、总抗氧化能力（T-AOC）均出现显著升高,但丙二醛（MDA）、终末氧化蛋白产物（AOPP）均显著降低（P<0.05）;治疗后,治疗组这些氧化产物和抗氧化指标显著优于对照组（P<0.05）。治疗后,治疗组的不良反应发生率是6.12%,显著低于对照组的20.40%（P<0.05）。结论 恩格列净联合吡格列酮在2型糖尿病患者中的防治效果显著,且可在一定程度上减少不良反应,同时能够明显改善患者氧化-抗氧化平衡,具有一定的临床推广应用价值。     

Association of plasma retinol-binding protein-4, adiponectin, and high molecular weight adiponectin with metabolic adversities in patients with schizophrenia

Objective

Metabolic adversities are prevalent in patients with schizophrenia. Retinol-binding protein 4 (RBP4) and high molecular weight (HMW) adiponectin have been recently found to be associated with metabolic features in non-psychiatric population. The study aimed to evaluate the associations between metabolic features and RBP4, total adiponectin, and HMW adiponectin in patients with schizophrenia.

Methods

We recruited 109 patients with schizophrenia treated with clozapine or haloperidol and evaluated their body mass index (BMI), waist circumference, blood pressure, and fasting triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose, insulin, RBP4, total adiponectin, and HMW adiponectin levels.

Results

We found that patients with metabolic syndrome (MS) had higher RBP4 level, and lower total adiponectin and HMW adiponectin levels than those without MS. There were no significant differences in metabolic features and adipocytokine levels between patients treated with clozapine and haloperidol. Most of the metabolic indexes were significantly correlated with the levels of adipocytokines. After adjusting the effects of age, gender, and BMI, marginal significant correlations existed between TG and RBP4 levels; HDL-C and total adiponectin and HMW adiponectin; insulin and HOMA-IR and HMW adiponectin. Receiver operating curve analysis showed that all of the three adipocytokines could differentiate patients with MS from those without MS. Meanwhile, total adiponectin and HMW adiponectin, but not RBP4, had the differentiating power for insulin resistance.

Conclusion

Higher RBP4 and lower total adiponectin and HMW adiponectin levels were observed in schizophrenic patients with MS. Only HMW adiponectin is marginally correlated with insulin sensitivity. The finding that metabolic profiles, but not the antipsychotic types, are associated with adipocytokine levels should be confirmed in longitudinal studies.     

Tissue sodium content in patients with type 2 diabetes mellitus

BackgroundTissue sodium content by ²³Na magnetic resonance imaging (MRI) has been found to be increased in arterial hypertension. We analyzed whether tissue sodium content is increased in patients with type-2 diabetes (T2DM).MethodsPatients with T2DM were compared to those with primary hypertension. Patients with T2DM were off any antidiabetic and hypertensive patients off any antihypertensive therapy for at least 4 weeks. Skin and muscle sodium content was assessed non-invasively with a 3.0 T clinical MRI system (Magnetom Verio, Siemens Health Care, Erlangen, Germany) in each patient.ResultsIn patients with T2DM (N = 59) we observed significantly greater muscle sodium content (diabetes: 20.6 ± 3.5 vs hypertension: 16.3 ± 2.5 mmol/l, p < 0.001) and skin sodium content (diabetes: 24.5 ± 7.2 vs hypertension: 20.6 ± 5.7 mmol/l, p = 0.01) than in those with primary hypertension (N = 33). When potential confounders (age, body mass index, gender, systolic and diastolic blood pressure, estimated glomerular filtration rate) were entered in a covariance analysis, both skin sodium content (p = 0.037) and muscle sodium content (p < 0.001) were still clearly elevated.ConclusionPatients with T2DM have greater skin and muscle sodium content. These are the first known data to demonstrate increased tissue sodium content in patients with T2DM, measured by ²³Na magnetic resonance imaging. Since tissue sodium content is related to organ damage, therapeutic intervention should aim at reducing tissue sodium content.     

Genetic association analyses of fast plasma glucose level in pre-menopausal Chinese women: potential interaction between osteocalcin and oestrogen receptor α

Background: Fasting plasma glucose (FPG) levels are usually tightly regulated within a narrow physiologic range. Variation of FPG levels is clinically important and is strongly heritable. Several lines of evidence suggest the importance of the oestrogen receptor α (ER-α) and osteocalcin (also known as BGP, for bone Gla protein) in determining FPG; however, whether their polymorphisms are associated with FPG variation is not well understood.

Aim: To investigate whether ER-a PvuII and BGP HindIII genetic polymorphisms and their potential interaction are associated with FPG variation.

Subjects and methods: The study subjects were 328 unrelated pre-menopausal Chinese women aged 21 years and over (mean age?±?SD, 33.2?±?5.9 years), with an average FPG of 4.92 (SD?=?0.81). All subjects were genotyped at the ER-α PvuII and BGP HindIII loci using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP).

Results: The ER-α PvuII genotypes were significantly associated with FPG (p?=?0.007). In addition, a significant interaction was observed of the ER-α PvuII polymorphism with BGP HindIII polymorphism on FPG variation (p?=?0.013), although the BGP HindIII polymorphism was not shown to be individually associated with FPG.

Conclusion: The PvuII polymorphism of the ER-α gene and its potential interaction with the HindIII polymorphism of the BGP gene were associated with FPG in pre-menopausal Chinese women.     

消糖灵胶囊联合利拉鲁肽治疗肥胖2型糖尿病的临床研究

目的 探讨消糖灵胶囊联合利拉鲁肽治疗肥胖2型糖尿病的临床疗效。方法 选择2019年12月—2021年6月在河北中石油中心医院治疗的120例肥胖2型糖尿病患者,随机分为对照组和治疗组,每组各60例。对照组早餐前皮下注射利拉鲁肽注射液,0.6 mg/次,1次/d。治疗组在对照组的基础上口服消糖灵胶囊,3片/次,2次/d。两组患者连续用药15周。观察两组患者临床疗效,比较治疗前后两组患者症状缓解时间,血糖指标空腹血糖（FPG）、餐后2 h血糖（2 h PBG）、糖化血红蛋白（Hb A1c）和空腹血清胰岛素（FINS）水平,血清因子肿瘤坏死因子-α(TNF-α)、可溶性血管细胞黏附因子-1(Svcam-1)、白细胞介素-6(IL-6)和超敏C反应蛋白（hs-CRP）水平,及不良反应。结果 治疗后,治疗组总有效率为98.33%,明显高于对照组的83.33%(P<0.05)。治疗后,治疗组多饮、多食、多尿、口干缓解时间均明显早于对照组（P<0.05）。治疗后,两组患者FPG、2 h FPG、HbA1c、FINS指标和血清因子TNF-α、Svcam-1、IL-6、hs-CRP水平均明显下...     

止渴养阴胶囊联合门冬胰岛素治疗2型糖尿病的临床研究

目的研究止渴养阴胶囊联合门冬胰岛素治疗2型糖尿病的临床疗效和安全性。方法选取2013年2月—2015年10月于延安市人民医院就诊的2型糖尿病患者86例,随机分成对照组和治疗组,每组各43例。对照组皮下注射门冬胰岛素注射液,起始剂量0.6 U/kg,每隔1~2天根据空腹血糖(FPG)和餐后2 h血糖(2 h PG)水平调整剂量。治疗组在对照组的基础上口服止渴养阴胶囊,3粒/次,3次/d。两组患者均连续治疗3个月。观察两组的临床疗效,同时比较两组治疗前后的FPG、2 h PG、Hb Alc、空腹C肽、2 h C肽水平、血糖达标时间、日血糖波动情况、日胰岛素用量以及低血糖发生率。结果治疗后,对照组和治疗组的总有效率分别为81.40%、95.35%,两组比较差异有统计学意义(P0.05)。治疗后FPG、2 h PG、Hb Alc水平下降,空腹C肽水平升高,同组治疗前后差异具有统计学意义(P0.05);且治疗组FPG、2 h PG、Hb Alc和空腹C肽水平改善程度优于对照组,差异具有统计学意义(P0.05)。治疗后治疗组血糖达标时间明显缩短,日胰岛素用量减少,低血糖发生率降低,两组比较差异有统计学意义(P0.05)。结论止渴养阴胶囊联合门冬胰岛素能够显著的提高2型糖尿病的治疗效果,减少日胰岛素用量少,降低低血糖发生率。