Antipsychotic Agents ; adverse effects ; Child ; Humans ; Hypoglycemic Agents ; therapeutic use ; Metabolic Syndrome ; drug therapy ; etiology ; Metformin ; therapeutic use ; Weight Gain

BACKGROUNDHyperinsulinemia and insulin resistance are present in the majority of women with polycystic ovary syndrome (PCOS). Both metformin and rosiglitazone can improve the ovulation and endocrine disorders of the patients. How about the combination of the two? It is rarely reported. This study aimed to compare the therapeutic efficacy of metformin versus metformin plus rosiglitazone in patients with PCOS.

METHODSFifty-eight women with PCOS were randomly assigned to two groups. Metformin group (29) was treated with metformin mono-therapy and metformin plus rosiglitazone group (29) was treated with metformin plus rosiglitazone for 6 months. Treatment was discontinued once pregnancy was diagnosed.

RESULTSFasting insulin, postprandial insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), triglyceride, lower density cholesterol and testosterone level decreased significantly in both groups (P < 0.05). Metformin plus rosiglitazone had a better effect than metformin mono-therapy. Body mass index decreased by 7.8% in metformin group while no significant change in metformin plus rosiglitazone group. There were eight pregnancies, six in metformin plus rosiglitazone group (one abortion) and two in metformin group. There was no congenital anomaly at birth and seven infants developed well at one year's follow-up.

CONCLUSIONSMetformin can improve insulin resistance and imbalance of endocrine hormones. Metformin plus rosiglitazone has a more pronounced therapeutic effect and achieved more pregnancies than mono-therapy with metformin. The use of metformin and rosiglitazone before pregnancy has no obvious side effect on the development of the infants. Our study might suggest that metformin is the better choice in PCOS patients with serious obese and rosiglitazone plus metformin would be more effective in patients with severe insulin resistance or those do not respond to metformin.

Adolescent ; Adult ; Female ; Humans ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Insulin Resistance ; physiology ; Luteinizing Hormone ; blood ; Metformin ; adverse effects ; therapeutic use ; Polycystic Ovary Syndrome ; blood ; drug therapy ; Testosterone ; blood ; Thiazolidinediones ; adverse effects ; therapeutic use ; Triglycerides ; blood ; Young Adult

We studied the efficacy and safety of acarbose in comparison with voglibose in type 2 diabetes patients whose blood glucose levels were inadequately controlled with basal insulin alone or in combination with metformin (or a sulfonylurea). This study was a 24-week prospective, open-label, randomized, active-controlled multi-center study. Participants were randomized to receive either acarbose (n=59, 300 mg/day) or voglibose (n=62, 0.9 mg/day). The mean HbA1c at week 24 was significantly decreased approximately 0.7% from baseline in both acarbose (from 8.43% +/- 0.71% to 7.71% +/- 0.93%) and voglibose groups (from 8.38% +/- 0.73% to 7.68% +/- 0.94%). The mean fasting plasma glucose level and self-monitoring of blood glucose data from 1 hr before and after each meal were significantly decreased at week 24 in comparison to baseline in both groups. The levels 1 hr after dinner at week 24 were significantly decreased in the acarbose group (from 233.54 +/- 69.38 to 176.80 +/- 46.63 mg/dL) compared with the voglibose group (from 224.18 +/- 70.07 to 193.01 +/- 55.39 mg/dL). In conclusion, both acarbose and voglibose are efficacious and safe in patients with type 2 diabetes who are inadequately controlled with basal insulin. (ClinicalTrials.gov number, NCT00970528)
Acarbose/adverse effects/*therapeutic use ; Blood Glucose ; Diabetes Mellitus, Type 2/blood/*drug therapy ; Enzyme Inhibitors/adverse effects/therapeutic use ; Female ; Hemoglobin A, Glycosylated/analysis ; Humans ; Hypoglycemic Agents/adverse effects/therapeutic use ; Inositol/adverse effects/*analogs & derivatives/therapeutic use ; Insulin/*blood/therapeutic use ; Male ; Metformin/therapeutic use ; Middle Aged ; Prospective Studies ; alpha-Glucosidases/antagonists & inhibitors

BACKGROUNDIncretin-based therapies provide additional options for treating type 2 diabetes. We aimed to evaluate the efficacy and tolerability of exenatide monotherapy in obese patients with type 2 diabetes.

METHODSA 26-week, metformin controlled, parallel-group study was conducted among antidiabetic drug-naive obese patients aged > 18 years, and with type 2 diabetes. Participating patients were randomly assigned to receive exenatide or metformin treatments.

RESULTSFifty-nine patients (age (50.5 ± 8.6) years, body mass index (BMI) (30.2 ± 1.6) kg/m(2), and hemoglobin A1C (HbA(1C) (8.2 ± 1.2)%) were enrolled in the study. Glucose control and weight reduction improved in both groups receiving treatment. HbA(1C) and oral glucose tolerance test (OGTT) 2 hour glycemia reduction with exenatide was superior to that obtained with metformin ((-2.10 ± 1.79)% vs. (-1.66 ± 1.38)%, (-5.11 ± 2.68) mmol/L vs. (-2.80 ± 2.70) mmol/L, P < 0.05). Fast plasma glucose (FPG) reduction was not significantly different between the two groups ((-1.8 ± 2.0) mmol/L vs. (-1.6 ± 1.7) mmol/L, P > 0.05). Patients treated with exenatide achieved HbA(1C) of < 7% (97% of patients) and < 6.5% (79%) at end-point, vs. 93% and 73% with metformin (P > 0.05). Greater weight reduction was also achieved with exenatide ((-5.80 ± 3.66) kg) than with metformin ((-3.81 ± 1.38) kg, P < 0.01). Homeostasis model assessment of beta-cell function (HOMA-B) was not significantly increased, but the insulinogenic index and HOMA for insulin sensitivity (HOMA-S) were greatly improved in the exenatide group (P < 0.05). Nausea was the most common adverse effect in exenatide treatment (30% vs. 8%; P < 0.05), but most cases were of mild to moderate intensity. One case in the exenatide group was withdrawn early because of severe nausea. Hypoglycemia events were often observed during the first 4 weeks, with 12% of patients in the exenatide and 3.2% in metformin groups, respectively (P < 0.05). No incidents of severe hypoglycemia were reported.

CONCLUSIONSExenatide demonstrated more beneficial effects on HbA(1C), weight reduction and insulin resistance during 26 weeks of treatment, but there were more hypoglycemic events and mild-to-moderate nausea compared with metformin. These results suggested that exenatide monotherapy may provide a viable treatment option in newly developed type 2 diabetes.

Adult ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemia ; chemically induced ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Insulin Resistance ; Male ; Metformin ; adverse effects ; therapeutic use ; Middle Aged ; Nausea ; chemically induced ; Obesity ; blood ; drug therapy ; Peptides ; adverse effects ; therapeutic use ; Venoms ; adverse effects ; therapeutic use ; Weight Loss ; drug effects

OBJECTIVETo perform meta-analyses evaluating the efficacy of adding Liuwei Dihuang Pills (, LDP) to Western medicine in improving treatment outcomes for type 2 diabetes.

METHODSMedline, PubMed, Cochrane Library, and Chinese databases, including the Chinese National Knowledge Infrastructure were searched to identify eligible studies; i.e., if the study involved a randomized clinical trial in which the experimental group combined LDP with Western drugs and the control group used the corresponding Western drugs alone to treat type 2 diabetes. Outcomes were measured in terms of fasting blood glucose (FBG), postprandial blood glucose (2hPG) and HbA1c level. Efficacy was also measured by using control and response rates. The combined odds ratio (OR), mean difference (MD), and 95% confidence intervals (95% CI) were calculated.

RESULTSStudies included in the analysis were less adequate than expected in terms of methodological quality. A total of 1,609 patients from 18 studies were included. We found that adding LDP can lower patients' FBG (MD=0.54 mmol/L, 95% CI [0.15, 0.93], P=0.007), 2hPG (MD=1.05 mmol/L, 95% CI [0.29, 1.81], P<0.01) and HbA1c (MD=0.23, 95% CI [0.02, 0.45], P=0.008). There were also improvements in treatment response rates (OR=3.41, 95% CI [2.38, 4.90], P<0.01) and control rates (OR=2.47, 95% CI [1.91, 3.20], P<0.01).

CONCLUSIONAdding LDP to Western medicine might improve treatment outcomes of diabetes, including FBG, 2hPG, response rates and control rates.

Blood Glucose ; metabolism ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Fasting ; blood ; Gliclazide ; adverse effects ; therapeutic use ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Metformin ; adverse effects ; therapeutic use ; Publication Bias ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Western World

Metformin is a kind of biguanide hypoglycemic agent that has been widely used in patients with diabetes mellitus. In clinical practice, whether metformin should be stopped before Fundus fluorescein angiography (FFA) remains largely unclear. Some endocrinologists suggest stop metformin before FFA. However, ophthalmologists do not always adopt this opinion in their practice. This situation may lead to disputes between physicians and patients. This article analyzed contrast-induced nephropathy(CIN) and the related contrast agent, as well as the adverse reactions of fluorescein angiography. It pointed out that the discrepancy may be caused by misunderstanding of contrast agents used in FFA. For angiography using iodine contrast agent, metformin must be stopped because of the increased possibility of CIN, while for FFA using fluorescein sodium, no CIN has been reported yet. Therefore, the authors believe FFA is safe for diabetic patients with oral metformin and it is unnecessary to stop metformin before the examination.
Administration, Oral ; Contrast Media ; adverse effects ; Diabetes Mellitus, Type 2 ; diagnostic imaging ; drug therapy ; Diabetic Retinopathy ; diagnostic imaging ; Fluorescein Angiography ; adverse effects ; methods ; Humans ; Hypoglycemic Agents ; therapeutic use ; Kidney Diseases ; chemically induced ; Metformin ; therapeutic use

BACKGROUNDAs one of most widely-used biguanides, metformin can induce the lactic acidosis in patients with renal failure though its incidence is very low. However, lactic acidemia induced by metformin was reported in patients without renal dysfunction. It is unclear that whether lactatemia exists in diabetic patients with normal renal function in Chinese or not and its influencing factors. This study aimed to clarify the influencing factors of lactic acid, and identify a practiced clinical marker to predict the hyperlactacidemia in diabetics with normal renal function.

METHODSThe clinical data and venous blood samples of 1024 type 2 diabetic patients treated with (n = 426) or without metformin (n = 599) were collected. The lactic acid was assayed by enzyme-electrode method. The biochemical indexes included creatinine (Cr) and hepatase were measured with enzymatic procedures. The lactic acid concentrations of different Cr subgroups were compared, and the correlation and receiver operating characteristic curve analysis were used.

RESULTSThe mean lactic acid level and the proportion of hyperlactatemia of metformin group were significantly higher than that of non-metformin group (P < 0.01), but no lactic acidosis was found in all patients. The correlation and multiple stepwise regression analysis indicated that the correlative factors of lactic acid in turn were Cr, metformin, alanine transferase (ALT), body mass index (BMI), Urine albumin (Ualb), and blood urea nitrogen (BUN) in total patients; and Cr, ALT, BMI and BUN in non-metformin treated patients; Cr and ALT in metformin-group. The lactate concentration increased with the increment of Cr levels, and reached its peak at Cr 111-130 micromol/L, and the optimal cutoff of Cr in predicting hyperlactacidemia was 96.5 micromol/L.

CONCLUSIONSMetformin can increase the incidence of lactatemia in type 2 diabetic patients without renal dysfunction. Cr, ALT, and BMI are independent associated factors of blood lactic acid levels. There is low proportion of lactatemia in type 2 diabetics without metformin therapy, the optimal cutoff of Cr to predict lactatemia in these patients is 96.5 micromol/L.

Adult ; Aged ; Aged, 80 and over ; Creatinine ; blood ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Female ; Humans ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Lactic Acid ; blood ; Male ; Metformin ; adverse effects ; therapeutic use ; Middle Aged ; Radioimmunoassay ; Young Adult

To examine the efficacy and safety for metformin in treating antipsychotic-induced dyslipidemia.
 Methods: Two randomized placebo-controlled trials were included in the analysis. A total of 201 schizophrenia patients with dyslipidemia after treatment with an antipsychotic were collected, and the patients were divided into two groups: a 1 000 mg/d metformin group (n=103) and a placebo group (n=98). The clinical symptoms and metabolic indicators such as body weight, blood glucose, and blood lipids were assessed at baseline, the 12th week and the 24th week after treatment respectively.
 Results: After metformin treatment, the mean difference in the low-density lipoprotein cholesterol (LDL-C) value between the metformin group and the placebo group was from 0.16 mmol/L at baseline to -0.86 mmol/L at the end of the 24th week, which was decreased by 1.02 mmol/L 
(P<0.01). At the 24th week, the LDL-C was more than 3.37 mmol/L in 25.3% patients in the metformin group, which was significantly lower than that in the placebo group (64.8%) (P<0.01). Compared with the placebo group, there were significant changes in the weight, body mass index (BMI), insulin, insulin resistance index, total cholesterol and triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the metformin group (all P<0.05). The treatment effects on weight and insulin resistance appeared at the 12th week and further improved at the 24th week, but the effects on improving dyslipidemia only significantly occurred at the end of the 24th week.
 Conclusion: The metformin treatment is effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effect to reduce the antipsychotic-induced insulin resistance appears earlier than the effect to improve dyslipidemia.
Antipsychotic Agents ; adverse effects ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Double-Blind Method ; Dyslipidemias ; chemically induced ; drug therapy ; Humans ; Hypoglycemic Agents ; Metformin ; therapeutic use

BACKGROUNDAt present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.

METHODSThis study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.

RESULTSAt week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.

CONCLUSIONSCompared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.

REGISTRATION NUMBERChiCTR-TRC-13003776.

Adult ; Blood Glucose ; drug effects ; C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drug Combinations ; Drug Therapy, Combination ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Metformin ; administration & dosage ; adverse effects ; therapeutic use ; Middle Aged ; Thiazoles ; administration & dosage ; adverse effects ; therapeutic use

BACKGROUNDFew studies have given suggestions on appropriate initiation insulin dosage when combined with oral antidiabetic drugs (OADs). This research was to investigate appropriate initiation insulin doses for insulin-naive type 2 diabetes patients with different combinations and the relationship between insulin dosage and relevant factors.

METHODSThis was a randomized, open-label, treat to target study. The target was 20% decrease of both fasting plasma glucose (FPG) and 2 hours post-breakfast blood glucose (P2hBG). One hundred and forty-seven insulin-naive Chinese patients recruited were randomly assigned to 3 groups: group A, patients received insulin monotherapy; group B, received insulin plus metformin (0.5 g, tid) and group C, received insulin plus metformin (0.5 g, tid) and pioglitazone (15 mg, qd). Insulin doses were initiated with a dose of 0.3 U×kg(-1)×d(-1) and titrated according to FPG and P2hBG till reached the targets.

RESULTSBoth the time of getting 20% reduction of FPG and P2hBG showed significant differences among the three groups. The time was shortest in Group C. The insulin doses needed to achieve glucose reduction of 20% in three treatment groups were (0.40 ± 0.04) U×kg(-1)×d(-1) for Group A, (0.37 ± 0.04) U×kg(-1)×d(-1) for Group B, and (0.35 ± 0.03) U×kg(-1)×d(-1) for Group C, respectively. Multiple linear stepwise regression analysis showed that insulin doses correlated with body weight, FPG, diabetes duration, age and history of sulfonylurea treatment. The standardized regression coefficients were 0.871, 0.322, 0.089, 0.067 and 0.063 (with all P < 0.05).

CONCLUSIONSTo achieve blood glucose's reduction of 20% within safety context, initial insulin doses were recommended as the following: 0.40 U×kg(-1)×d(-1) for insulin mono-therapy, 0.37 U×kg(-1)×d(-1) for insulin plus metformin treatment, and 0.35 U×kg(-1)×d(-1) for insulin plus metformin and pioglitazone treatment in Chinese type 2 diabetes outpatients. Body weight is found the most closely related factor to the insulin dosage.

Adult ; Aged ; Blood Glucose ; analysis ; Body Weight ; drug effects ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drug Therapy, Combination ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; Insulin ; administration & dosage ; adverse effects ; therapeutic use ; Linear Models ; Male ; Metformin ; administration & dosage ; adverse effects ; Middle Aged ; Outpatients ; Regression Analysis ; Thiazolidinediones ; administration & dosage ; adverse effects