OBJECTIVE: Behcet's disease (BD) is an autoimmune disorder that causes most commonly mouth and genital ulcerations and erythema nodules of the skin and currently has limited options of therapeutic medicines. Metformin is recently reported to suppress immune reaction, and we hypothesized that metformin could be an option for treatment of BD. METHODS: Thirty patients with BD were enrolled in this perspective single-blinded, before-after study. We recorded the changes in the mucocutaneous activity index for BD (MAIBD), relapse frequency, C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) after metformin treatment to assess the changes in the disease activity. We also analyzed the changes in the protein and mRNA expression levels of Foxp3, interleukin-35 (IL-35), transforming growth factor-β (TGF-β), Ror-γt, IL-17, and tumor necrosis factor- (TNF-) in these patients using ELISA and qRT-PCR. RESULTS: Of the 30 patients enrolled, 26 completed the trial. After the treatment, favorable responses were achieved in 88.46% (23/26) of the patients, and partial remission was obtained in 11.54% (4/26) of them. During the treatment, 8 patients complained of gastrointestinal side effects, for which 4 chose to withdraw from the study in the first week. Our results showed that metformin treatment decreased MAIBD and relapse frequency in the patients, and significantly lowered the clinical inflammatory indexes including CRP and ESR. The results of ELISA and qRT-PCR revealed that metformin treatment obviously increased Foxp3 and TGF-β expressions at both the protein and mRNA levels and significantly decreased the levels of ROR-γt, IL-17 and TNF- as well as IL-35 level in these patients. CONCLUSIONS Metformin treatment relieves the clinical symptoms, reduces the inflammatory reaction indexes and regulates the Treg/Th17 axis in patients with BD, suggesting the potential of metformin as a candidate medicine for treatment of BD.
Behcet Syndrome ; drug therapy ; metabolism ; Controlled Before-After Studies ; Forkhead Transcription Factors ; metabolism ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Interleukin-17 ; metabolism ; Interleukins ; metabolism ; Metformin ; adverse effects ; therapeutic use ; Neoplasm Recurrence, Local ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; metabolism ; RNA, Messenger ; metabolism ; Recurrence ; Single-Blind Method ; T-Lymphocytes, Regulatory ; cytology ; Th17 Cells ; cytology ; Transforming Growth Factor beta ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

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

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

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

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

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

We evaluated the prevalence of vitamin B12 deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B12 and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12 < or = 300 pg/mL without folate deficiency (folate > 4 ng/mL). The prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B12 level was 662.5 +/- 246.7 pg/mL. Vitamin B12 deficient patients had longer duration of metformin use (P < 0.001) and higher daily metformin dose (P < 0.001) than non-deficient patients. Compared with daily metformin dose of < or = 1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and > or = 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80 (95% CI, 1.82-7.92, P < 0.001). Compared with metformin use of < 4 yr, the adjusted odds ratios for 4-10 yr, and > or = 10 yr were 4.65 (95% CI, 2.36-9.16, P < 0.001) and 9.21 (95% CI, 3.38-25.11, P < 0.001), respectively. In conclusion, our study indicates that patients with type 2 diabetes treated with metformin should be screened for vitamin B12 deficiency, especially at higher dosages (> 1,000 mg) and longer durations (> or = 4 yr) of treatment.
Aged ; Area Under Curve ; Diabetes Mellitus, Type 2/complications/diagnosis/*drug therapy ; Female ; Folic Acid/blood ; Humans ; Hypoglycemic Agents/adverse effects/*therapeutic use ; Immunoassay ; Male ; Metformin/adverse effects/*therapeutic use ; Middle Aged ; Odds Ratio ; Patients ; Prevalence ; ROC Curve ; Time Factors ; Vitamin B 12/blood ; Vitamin B 12 Deficiency/diagnosis/epidemiology/*etiology

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

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

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