Qiu-Mei Zhang

Efficacy and safety comparison between liraglutide as add-on therapy to insulin and insulin dose-increase in Chinese subjects with poorly controlled type 2 diabetes and abdominal obesity

ObjectiveTo assess the efficacy and safety of adding liraglutide to established insulin therapy in poorly controlled Chinese subjects with type 2 diabetes and abdominal obesity compared with increasing insulin dose.MethodsA 12-week, randomized, parallel-group study was carried out. A total of 84 patients completed the trial who had been randomly assigned to either the liraglutide-added group or the insulin-increasing group while continuing current insulin based treatment. Insulin dose was reduced by 0-30% upon the initiation of liraglutide. Insulin doses were subsequently adjusted to optimized glycemic control. Glycosylated hemoglobin (HbA1c) values, blood glucose, total daily insulin dose, body weight, waist circumference, and the number of hypoglycemic events and adverse events were evaluated.ResultsAt the end of study, the mean reduction in HbA1c between the liraglutide-added group and the insulin-increasing group was not significantly different (1.9% vs. 1.77%, p>0.05). However, the percentage of subjects reaching the composite endpoint of HbA1c ≤ 7.0% with no weight gain and no hypoglycemia, was significantly higher in the liraglutide-added group than in the insulin-increasing group (67% vs. 19%, p<0.001). Add-on liraglutide treatment significantly reduced mean body weight (5.62 kg, p<0.01), waist circumference (5.70 cm, p<0.01), body mass index (BMI) (1.93 kg/m2, p<0.01) and daily total insulin dose (dropped by 66%) during 12-week treatment period, while all of these significantly increased with insulin increasing treatment. Add-on liraglutide treated patients had lower rate of hypoglycemic events and greater insulin and oral antidiabetic drugs discontinuation. Gastrointestinal disorders were the most common adverse events in the liraglutide added treatment, but were transient.ConclusionsAddition of liraglutide to abdominally obese, insulin-treated patients led to improvement in glycemic control similar to that achieved by increasing insulin dosage, but with a lower daily dose of insulin and fewer hypoglycemic events. Adding liraglutide to insulin also induced a significant reduction in body weight and waist circumference. Liraglutide combined with insulin may be the best treatment option for poorly controlled type 2 diabetes and abdominal obesity.

Changes in liraglutide-induced body composition are related to modifications in plasma cardiac natriuretic peptides levels in obese type 2 diabetic patients

Background and aimsLiraglutide treatment can improve glycemic control with a concomitant weight loss, but the underlying mechanism on weight loss is not completely understood. Cardiac natriuretic peptides (NPs) can resist body fat accumulation through increasing adipocytes lypolysis. In this study, we tested the hypothesis that liraglutide-induced weight loss was associated with increased plasma NPs concentrations.MethodsThirty-one outpatients with type 2 diabetes (T2D) treated with metformin and other oral antidiabetic drugs except for thiazolidinediones (TZDs) were subcutaneously administered with liraglutide for 12 weeks. Body composition, abdominal visceral adipose tissue areas (VAT) and subcutaneous adipose tissue areas (SAT) were assessed at pre- and post-treatment by dual-energy X-ray absorptiometry (DXA) scanning and abdominal computerized tomography (CT). Plasma atrial natriuretic peptides (ANP) and B-type ventricular natriuretic peptides (BNP) concentrations were tested by commercial ELISA Kit quantitatively.ResultsFollowing 12-week liraglutide treatment, body weight, waist circumference, total fat and lean mass, fat percentage, SAT and VAT areas were significantly reduced from baseline. Concurrently, plasma ANP and BNP levels were significantly increased following 12-week liraglutide treatment. There were significant correlations between the reductions in body compositions and the increases in both plasma ANP and BNP levels.ConclusionsThere were significant correlations between increases in both plasma ANP and BNP levels and changes in liraglutide-induced body composition. Our data implied that increases in plasma NPs may add a novel dimension to explain how liraglutide induces weight loss.

Efficacy and safety comparison of add-on therapy with liraglutide, saxagliptin and vildagliptin, all in combination with current conventional oral hypoglycemic agents therapy in poorly controlled Chinese type 2 diabetes.

To compare the efficacy and safety of adding liraglutide, saxagliptin and vildagliptin to current therapy in Chinese type 2 diabetes subjects with poor glycemic control.A 24-week, randomized, open-label, parallel clinical trial was performed. A total 178 patients completed the trial who had been randomly assigned to add-on once daily liraglutide (1.2 mg/day injected subcutaneously), to saxagliptin (5 mg once daily) or to vildagliptin (50 mg twice daily). Glycosylated hemoglobin (HbA1c) values, fasting and postprandial blood glucose (FBG and P2BG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated.Over the 24-week treatment period, greater lowering of mean of HbA1c was achieved with 1.2 mg liraglutide (-1.50%, 95% CI [-1.67, -1.34]) than with saxagliptin (-1.23%, 95% CI [-1.36, -1.11]) and vildagliptin (-1.25%, 95% CI [-1.37, -1.13]). There was no significant between-group difference of percentages of subjects who reached a target HbA1c<7.0%, but significantly more subjects with liraglutide achieved HbA1c≤6.5% compared with saxagliptin and vildagliptin. The mean reduction of FBG value from baseline was 2.23 mmol/L with liraglutide, much greater than 1.83 mmol/L with saxagliptin (p=0.013), but similar to 2.03 mmol/L with -vildaglitpin group. As to the P2BG value, greater reductions was found with liraglutide (-4.80 mmol/L) than -3.56 mmol/L with saxagliptin (p=0.000) and -3.57 mmol/L with vildagliptin (p=0.000). Moreover, greater mean reductions of body weight and BMI with liraglutide (-6.0 kg and -2.1 kg/m(2)) were achieved than with saxagliptin and vildagliptin (both p<0.001), whereas no significant difference was found between saxagliptin and vildagliptin group. The incidence of hypoglycemia was recorded low and similar in each treatment group. Nausea was more common with liraglutide (27%) than with saxagliptin (3.2%) and vildagliptin (5.2%), but no significant between-group difference was reported in other AEs.Adding liraglutide demonstrated superiority to saxagliptin and vildagliptin for reductions of HbA1c and weight loss in Chinese subjects with T2DM who had inadequate glycemic control with conventional oral hypoglycemic agents. These findings support the add-on of liraglutide could offer notable advantages over DPP-4 inhibitors in both efficacy and safety.

Adding glimepiride to current insulin therapy increases high-molecular weight adiponectin levels to improve glycemic control in poorly controlled type 2 diabetes

BackgroundTo observe the efficacy and safety of adding glimepiride to established insulin therapy in poorly controlled type 2 diabetes (T2D) and to assess the relationship of changes in the serum high-molecular weight (HMW) adiponectin levels and glycemic control after glimepiride treatment.MethodsFifty-six subjects with poorly controlled insulin-treated T2D were randomly assigned to either the glimepiride-added group (the group A, n = 29) or the insulin-increasing group (the group B, n = 27) while continuing current insulin-based therapy. Glycosylated hemoglobin (HbA1c) value, daily insulin dose, body weight, waist circumference, plasma lipid concentration, serum HMW adiponectin level and the number of hypoglycemic events were evaluated before and after treatment.ResultsAt the end of study, insulin doses were significantly reduced, and the mean HbA1c, fasting blood glucose (FBG) and 2-hour postprandial blood glucose (P2BG) were improved greater in the group A compared with the group B. The serum HMW adiponectin levels were significantly increased in the group A compared with the group B. Most importantly, we found that changes in HbA1c were inversely correlated with changes in serum HMW adiponectin in the group A (r = −0.452, p = 0.02).ConclusionsAdding glimepiride to current insulin treatment led to better improvement in glycemic control with a significant smaller daily insulin dose, and the increases in the serum HMW adiponectin levels may directly contribute to improvement glycemic control.

Association of Thyroid-Stimulating Hormone Levels with Microvascular Complications in Type 2 Diabetes Patients

Background Subclinical hypothyroidism (SCH) is typically featured by elevated serum concentration of thyroid-stimulating hormone (TSH). This study aimed to determine the relationship between TSH levels and microvascular complications in type 2 diabetes patients. Material/Methods A total of 860 type 2 diabetes patients were enrolled in this cross-sectional study. Subjects were evaluated for anthropometric measurements, thyroid function, diabetic retinopathy, and diabetic kidney disease. TSH was divided into 3 levels: 0.27–2.49 mU/l, 2.5–4.2 mU/l, and >4.2 mU/l. Results Among the participants, 76 subjects (8.8%) were diagnosed with subclinical hypothyroidism (SCH) (male: 6.6% and female: 11.8%). The prevalence of diabetic retinopathy did not differ among the groups (P=0.259). Of the 860 type 2 diabetic subjects, we further excluded invalid or missing data. Therefore, 800 and 860 subjects were included in our study of diabetic retinopathy (DR) and diabetic kidney disease (DKD), respectively. The frequencies of microalbuminuria and macroalbuminuria differed significantly among the different groups. The frequency of DKD was significantly different among the 3 groups (P=0.001) and was higher in subjects with higher TSH levels. After an adjustment for confounding variables, TSH levels were significantly associated with DKD (P<0.001). When compared with subjects with TSH 0.27–2.49 mU/l, the frequency of DKD was higher in subjects with TSH >4.20 mU/l (OR 1.531, 95% CI 1.174–1.997) and with TSH 2.50–4.20 mU/l (OR 1.579, 95% CI 1.098–2.270). However, TSH levels was not significantly correlated with DR (P=0.126). Conclusions Type 2 diabetic patients with higher TSH values had a higher prevalence of DKD.

Serum adipocyte fatty acid‐binding protein levels are associated with peripheral arterial disease in women, but not men, with type 2 diabetes mellitus

Adipocyte fatty acid‐binding protein (A‐FABP) has been recognized as an important player in macrophage cholesterol trafficking and inflammation, and may promote the development of atherosclerosis. To further elucidate the role of A‐FABP in atherosclerosis in diabetes, we investigated the relationship between serum A‐FABP concentrations and peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM).