METHODS: We performed systematic searches using electronic databases including PubMed and EMBASE until December 2012. Key words included "metformin" AND ("ovarian cancer" OR "ovary tumor"). All human studies assessing the effects of metformin on ovarian cancer were eligible for inclusion. All articles were reviewed independently by 2 authors with a standardized approach for the purpose of study, study design, patient characteristics, exposure, and outcomes. The data were pooled using a random-effects model.
RESULTS: Of 190 studies retrieved, only 3 observational studies and 1 report of 2 randomized controlled trials were included. Among those studies, 2 reported the effects of metformin on survival outcomes of ovarian cancer, whereas the other 2 reported the effects of metformin on ovarian cancer prevention. The findings of studies reporting the effects on survival outcomes indicated that metformin may prolong overall, disease-specific, and progression-free survival in ovarian cancer patients. The results of studies reporting the effects of metformin on ovarian cancer prevention were meta-analyzed. It indicated that metformin tended to decrease occurrence of ovarian cancer among diabetic patients with the pooled odds ratio of 0.57 (95% confidence interval, 0.16-1.99).
CONCLUSIONS: Our findings showed the potential therapeutic effects of metformin on survival outcomes of ovarian cancer and ovarian cancer prevention. However, most of the evidence was observational studies. There is a call for further well-conducted controlled clinical trials to confirm the effects of metformin on ovarian cancer survival and ovarian cancer prevention.
AIMS: To examine the trends in prescribed antidiabetic treatments, including variations across age, gender, socioeconomic status and regions in the Irish population over the last 10 years.
METHODS: The Irish national pharmacy claims database was used to identify patients ≥ 16 years dispensed antidiabetic agents (oral or insulin) from January 2003 to December 2012 through the two main community drug schemes for diabetes. The rate of prescribing per 1,000 population was calculated. Logistic regression was used to examine variations in prescribing in patients with diabetes.
RESULTS: There was a significant increase in the prescribing of fast and long-acting insulin analogues with a rapid decline in the prescribing of human insulin (p < 0.0001). Increased prescribing of metformin, incretin modulators and fixed oral combination agents was observed (p < 0.0001). Females and older aged patients were more likely to be prescribed human insulin than other insulins. Metformin was less likely while sulphonylureas were more likely to be prescribed in older than younger aged patients. Socioeconomic differences were observed in increased prescribing of the newer and more expensive antidiabetic agents in the non-means tested scheme. Regional variations were observed in the prescribing of both insulin and oral antidiabetic agents.
CONCLUSION: There has been an increase over time in the prescribing of both insulin and oral antidiabetic agents in the Irish population with increasing uptake of newer antidiabetic agents. This has implications for projecting future uptake and expenditure of these agents given the rising level of diabetes in the population.
OBJECTIVES: To assess the effects of mormodica charantia for type 2 diabetes mellitus.
SEARCH METHODS: Several electronic databases were searched, among these were The Cochrane Library (Issue 1, 2012), MEDLINE, EMBASE, CINAHL, SIGLE and LILACS (all up to February 2012), combined with handsearches. No language restriction was used.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared momordica charantia with placebo or a control intervention, with or without pharmacological or non-pharmacological interventions.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. Risk of bias of the trials was evaluated using the parameters of randomisation, allocation concealment, blinding, completeness of outcome data, selective reporting and other potential sources of bias. A meta-analysis was not performed given the quality of data and the variability of preparations of momordica charantia used in the interventions (no similar preparation was tested twice).
MAIN RESULTS: Four randomised controlled trials with up to three months duration and investigating 479 participants met the inclusion criteria. Risk of bias of these trials (only two studies were published as a full peer-reviewed publication) was generally high. Two RCTs compared the effects of preparations from different parts of the momordica charantia plant with placebo on glycaemic control in type 2 diabetes mellitus. There was no statistically significant difference in the glycaemic control with momordica charantia preparations compared to placebo. When momordica charantia was compared to metformin or glibenclamide, there was also no significant change in reliable parameters of glycaemic control. No serious adverse effects were reported in any trial. No trial investigated death from any cause, morbidity, health-related quality of life or costs.
AUTHORS' CONCLUSIONS: There is insufficient evidence on the effects of momordica charantia for type 2 diabetes mellitus. Further studies are therefore required to address the issues of standardization and the quality control of preparations. For medical nutritional therapy, further observational trials evaluating the effects of momordica charantia are needed before RCTs are established to guide any recommendations in clinical practice.
Subjects and methods: Sixty T2DM patients were recruited in a randomized, placebo-controlled, double-blinded, and multicenter trial. The patients, currently using Met, were randomly grouped into those treated with either GKB extract (120 mg/day) or placebo (starch, 120 mg/day) for 90 days. Blood glycated hemoglobin (HbA1c), fasting serum glucose, serum insulin, body mass index (BMI), waist circumference (WC), insulin resistance, and visceral adiposity index (VAI) were determined before (baseline) and after 90 days of GKB extract treatment.
Results: GKB extract significantly decreased blood HbA1c (7.7%±1.2% vs baseline 8.6%±1.6%, P<0.001), fasting serum glucose (154.7±36.1 mg/dL vs baseline 194.4±66.1 mg/dL, P<0.001) and insulin (13.4±7.8 μU/mL vs baseline 18.5±8.9 μU/mL, P=0.006) levels, BMI (31.6±5.1 kg/m2 vs baseline 34.0±6.0 kg/m2, P<0.001), waist WC (102.6±10.5 cm vs baseline 106.0±10.9 cm, P<0.001), and VAI (158.9±67.2 vs baseline 192.0±86.2, P=0.007). GKB extract did not negatively impact the liver, kidney, or hematopoietic functions.
Conclusion: GKB extract as an adjuvant was effective in improving Met treatment outcomes in T2DM patients. Thus, it is suggested that GKB extract is an effective dietary supplement for the control of DM in humans.
METHODS: We assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome).
RESULTS: Fasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels.
CONCLUSION: Serum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c.
METHODS: This open-label, parallel-group, 26-week, multicentre, treat-to-target trial, randomly allocated participants (1:1) to two titration arms. The Simple algorithm titrated IDegAsp twice weekly based on a single pre-breakfast self-monitored plasma glucose (SMPG) measurement. The Stepwise algorithm titrated IDegAsp once weekly based on the lowest of three consecutive pre-breakfast SMPG measurements. In both groups, IDegAsp once daily was titrated to pre-breakfast plasma glucose values of 4.0-5.0 mmol/l. Primary endpoint was change from baseline in HbA1c (%) after 26 weeks.
RESULTS: Change in HbA1c at Week 26 was IDegAspSimple -14.6 mmol/mol (-1.3%) (to 52.4 mmol/mol; 6.9%) and IDegAspStepwise -11.9 mmol/mol (-1.1%) (to 54.7 mmol/mol; 7.2%). The estimated between-group treatment difference was -1.97 mmol/mol [95% confidence interval (CI) -4.1, 0.2] (-0.2%, 95% CI -0.4, 0.02), confirming the non-inferiority of IDegAspSimple to IDegAspStepwise (non-inferiority limit of ≤ 0.4%). Mean reduction in fasting plasma glucose and 8-point SMPG profiles were similar between groups. Rates of confirmed hypoglycaemia were lower for IDegAspStepwise [2.1 per patient years of exposure (PYE)] vs. IDegAspSimple (3.3 PYE) (estimated rate ratio IDegAspSimple /IDegAspStepwise 1.8; 95% CI 1.1, 2.9). Nocturnal hypoglycaemia rates were similar between groups. No severe hypoglycaemic events were reported.
CONCLUSIONS: In participants with insulin-naïve Type 2 diabetes mellitus, the IDegAspSimple titration algorithm improved HbA1c levels as effectively as a Stepwise titration algorithm. Hypoglycaemia rates were lower in the Stepwise arm.
METHODS: A double blind randomized trial. 103 women scheduled to receive two doses of 12-mg intramuscular dexamethasone 12-hour apart were separately randomized to take prophylactic metformin or placebo after stratification according to their gestational diabetes (GDM) status. First oral dose of allocated study drug was taken at enrolment and continued 500 mg twice daily for 72 hours if not delivered. Six-point blood sugar profiles were obtained each day (pre- and two-hour post breakfast, lunch and dinner) for up to three consecutive days. A hyperglycemic episode is defined as capillary glucose fasting/pre-meal ≥ 5.3 mmol/L or two-hour post prandial/meal ≥ 6.7 mmol/L. Primary outcome was hyperglycemic episodes on Day-1 (first six blood sugar profile points) following antenatal corticosteroids.
RESULTS: Number of hyperglycemic episodes on the first day were not significantly different (mean ± standard deviation) 3.9 ± 1.4 (metformin) vs. 4.1 ± 1.6 (placebo) p = 0.64. Hyperglycemic episodes markedly reduced on second day in both arms to 0.9 ± 1.0 (metformin) vs. 1.2 ± 1.0 (placebo) p = 0.15 and further reduced to 0.6 ± 1.0 (metformin) vs. 0.7 ± 1.0 (placebo) p = 0.67 on third day. Hypoglycemic episodes during the 3-day study period were few and all other secondary outcomes were not significantly different.
CONCLUSIONS: In euglycemic and diet controllable gestational diabetes mellitus women, antenatal corticosteroids cause sustained maternal hyperglycemia only on Day-1. The magnitude of Day-1 hyperglycemia is generally low. Prophylactic metformin does not reduce antenatal corticosteroids' hyperglycemic effect.
TRIAL REGISTRATION: The trial is registered in the ISRCTN registry on May 4 2017 with trial identifier https://doi.org/10.1186/ISRCTN10156101 .
MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into 5 groups, namely: normal control (NC), diabetic control (DC), diabetic on 300 mg/kg b.w. MP, diabetic on 300 mg/kg b.w. metformin, and diabetic on MP and metformin combined therapy. Treatment was done orally for 4 weeks, and NC and DC groups received distilled water as vehicle.
KEY FINDINGS: Results showed increased fasting blood glucose and serum markers of hepatic lesion (aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase and gamma-glutamyl transferase), increased hepatic lactate dehydrogenase activity, decreased hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase activities, increased immunoexpressions of nuclear factor kappa B, tumor necrosis factor-α, interleukin(IL)-1β and caspase-3, and decreased immunoexpressions of IL-10 and proliferating cell nuclear antigen in the liver of DC group. Histopathology of the liver revealed numerous hepatocytes with pyknotic nuclei and inflammatory infiltration, while periodic acid-schiff staining decreased in the liver of DC group. Treatment with MP attenuated these negative effects and was comparable to metformin. Furthermore, these effects were better attenuated in the combined therapy-treated diabetic rats.
SIGNIFICANCE: Malaysian propolis attenuates hepatic lesion in DM and exerts a synergistic protective effect with the anti-hyperglycemic medication, metformin.
OBJECTIVES: To compare the clinical effectiveness of combined therapy using SGLT2 inhibitor and metformin with monotherapy using metformin alone in HbA1c and body weight reduction.
METHOD: A systematic review of the randomized controlled trials has been carried out and Cochrane risk of bias tool was used for the quality assessment. Patient, Intervention, Comparison and Outcomes (PICO) technique is used to select the relevant articles to meet the objective.
RESULTS: The studies used in this article are multicenter, double-blinded randomized controlled trials on SGLT2 inhibitors with methformin, there were a total of 3897 participants, with a range of 182 to 1186 individual study size were included. Studies showed that combined therapy were more effective in HbA1c and body weight reduction as compared to monotherapy.
CONCLUSION: The combined therapy of SGLT2 inhibitor along with metformin is more effective in HbA1c reduction and weight reduction as compared to monotherapy using metformin alone. Among the three SGLT2 inhibitors such as dapagliflozin canagliflozin and empagliflozin do not differ much in the efficiency of weight reduction. However, Empagliflozin 25mg is effective in HbA1c reduction.