Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new glucophage research articles will be listed here shortly after becoming available to us.
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Am J Chin Med. 2008; 36(6): 1083-104
Waisundara VY, Huang M, Hsu A, Huang D, Tan BK
This study investigated the effects of Rehmannia glutinosa individually as well as in combination with the oral hypoglycemic agent, metformin in streptozotocin (STZ)-induced diabetic Wistar rats. R. glutinosa ethanolic extract was prepared and the constituents were characterized using fractionation by column chromatography, followed by high performance liquid chromatography-mass spectrometry. STZ (65 mg/kg) was injected intraperitoneally to induce diabetes in Wistar rats. The diabetic rats were divided into the following groups (each n = 6) and received the respective treatments for 30 days: (1) metformin (500 mg/kg), (2) R. glutinosa (200 mg/kg), (3) metformin (500 mg/kg) and R. glutinosa (200 mg/kg) and (4) diabetic control (DC). A reduction in plasma glucose levels caused by the herb was not as significant as metformin compared to the diabetic control (p < 0.05). However, R. glutinosa-treated group showed reductions in plasma C-reactive protein (CRP) levels compared to the diabetic controls (p < 0.05) as well as metformin-treated group (p < 0.05). An enhanced reduction in CRP concentration was observed in the group receiving both herb and metformin compared to metformin-treated group (p < 0.05). Reduction in CRP levels suggests an anti-inflammatory activity of the herb.
Diabetes Metab. 2008 Nov 27;
Bringer J, Fontaine P, Detournay B, Nachit-Ouinekh F, Brami G, Eschwege E
AIMS: To estimate the prevalence of diagnosed type 2 diabetes mellitus in the French general population. Secondary objectives were to evaluate treatments and diabetic complications. METHODS: In this cross-sectional epidemiological survey, a representative sample of the French adult population was selected using a stratified quota method: 10,038 individuals were evaluated by a standardized face-to-face interview. The diagnosis of type 2 diabetes was determined on the basis of replies to six questions using a specific algorithm. Data were collected on risk factors, diabetes history, familial antecedents and diabetic complications. These patients also identified their treatments from an exhaustive list. RESULTS: The prevalence of type 2 diabetes was 5.08% in men and 4.11% in women, and rose progressively after the age of 50. Of these, 79patients (13.4%) received no pharmacological treatment, 477 (80.9%) were taking an oral antidiabetic drug and 134 (22.7%) were taking insulin. Renal and ocular complications were reported by 6.8% and 21.0%, respectively, of the patients. Also, 10.4% had been hospitalized at some time of that year for a diabetes-related problem. The most frequently reported treatments were metformin and sulphonylureas, used by more than 50% of the patients. In addition, 380 patients (65.9%) claimed to be following a diet and 228 (39.2%) were consulting a dietitian. CONCLUSION: The prevalence of treated and untreated type 2 diabetes mellitus in France was 4.57%.
J Mol Signal. 2008 Dec 1; 3(1): 18
Zhuang Y, Miskimins WK
ABSTRACT: BACKGROUND: The antihyperglycemic drug metformin may have beneficial effects on the prevention and treatment of cancer. Metformin is known to activate AMP-activated protein kinase (AMPK). It has also been shown to inhibit cyclin D1 expression and proliferation of some cultured cancer cells. However, the mechanisms of action by which metformin mediates cell cycle arrest are not completely understood. Results: In this study, metformin was found to inhibit proliferation of most cultured breast cancer cell lines. This was independent of estrogen receptor, HER2, or p53 status. Inhibition of cell proliferation was associated with arrest within G1 phase of the cell cycle. As in previous studies, metformin treatment led to activation of (AMPK) and downregulation of cyclin D1. However, these events were not sufficient for cell cycle arrest because they were also observed in the MDA-MB-231 cell line, which is not sensitive to growth arrest by metformin. In sensitive breast cancer lines, the reduction in cyclin D1 led to release of sequestered CDK inhibitors, p27Kip1 and p21Cip1, and association of these inhibitors with cyclin E/CDK2 complexes. The metformin-resistant cell line MDA-MB-231 expresses significantly lower levels of p27Kip1 and p21Cip1 than the metformin-sensitive cell line, MCF7. When p27Kip1 or p21Cip1 were overexpressed in MDA-MB-231, the cells became sensitive to cell cycle arrest in response to metformin. Conclusions: Cell cycle arrest in response to metformin requires CDK inhibitors in addition to AMPK activation and cyclin D1 downregulation. This is of interest because many cancers are associated with loss or downregulation of CDK inhibitors and the results may be relevant to the development of anti-tumor reagents that target the AMPK pathway.
Emerging dipeptidyl peptidase-4 inhibitors for the treatment of diabetes.
Expert Opin Emerg Drugs. 2008 Dec; 13(4): 593-607
Ahrén B
Inhibition of dipeptidyl peptidase-4 (DPP-4) prevents the inactivation of glucagon-like peptide-1 (GLP-1). This increases circulating levels of active GLP-1, stimulates insulin secretion and inhibits glucagon secretion, resulting in lowering of glucose levels and improvement of glycemic control in patients with type 2 diabetes. Several DPP-4 inhibitors are emerging for therapeutic use. Most experience exists for sitagliptin, vildagliptin, saxagliptin and alogliptin. They all improve metabolic control in type 2 diabetes in monotherapy and in combination therapy with metformin, sulfonylurea and thiazolidinediones. Vildagliptin and alogliptin have also been shown to improve glycemic control when added to insulin therapy, and sitagliptin improves glycemic control in triple therapy with metformin plus thiazolidinedione. DPP-4 inhibition also shows a favorable safety profile, high tolerability, only a minimal risk of hypoglycemia, and body-weight neutrality. The main clinical indication for DPP-4 inhibitors will be in the early stage of type 2 diabetes, in combination with metformin or other treatments in subjects with inadequate glycemic control on these treatments alone. The durability and long-term safety of DPP-4 inhibition, as well as clinical positioning in relation to GLP-1 mimetics, remain now to be established.
Med Hypotheses. 2008 Nov 25;
Cohen P
Metformin-associated lactic acidosis in intensive care unit.
Crit Care. 2008 Nov 26; 12(6): R149
Peters N, Jay N, Cravoisy A, Barraud D, Nace L, Bollaert PE, Gibot S
ABSTRACT: INTRODUCTION: Metformin-associated lactic acidosis (MALA) is a classical side effect of metformin and is known to be a severe disease with a high mortality rate. MALA's treatment by dialysis is controversial and is subject to many case reports. We aimed to assess the prevalence of MALA in a 16-bed, university-affiliated, intensive care unit (ICU), and the effect of dialysis on patients' outcome. METHODS: Over a 5-year period, we retrospectively identified all patients who either were admitted into the ICU with metformin as a usual medication, or who attempted suicide by metformin ingestion. Within this population, we selected patients presenting with a lactic acidosis, thus defining MALA, and described their clinical and biological features. RESULTS: Metformin-associated lactic acidosis accounted for 0.84% of all admissions during the studied period (30 MALA admissions over 5 years) and was associated with a 30% mortality rate. The only factors associated with a fatal outcome were the reason for admission in the ICU and the initial prothrombin time. Although patients who went on to hemodialysis had higher illness severity scores, as compared to those who were not dialyzed, the mortality rates were similar between the two groups (31.3% versus 28.6%). CONCLUSIONS: Metformin-associated lactic acidosis can be encountered in the ICU several times a year and still remains a life-threatening condition. Treatment is mostly restricted to supportive measures, although hemodialysis may possess a protective effect.
The citrus fruit flavonoid naringenin suppresses hepatic glucose production from Fao hepatoma cells.
Mol Nutr Food Res. 2008 Nov 26;
Purushotham A, Tian M, Belury MA
Hepatic gluconeogenesis is the major source of fasting hyperglycemia. Here, we investigated the role of the citrus fruit flavonoid naringenin, in the attenuation of hepatic glucose production from hepatoma (Fao) cells. We show that naringenin, but not its glucoside naringin, suppresses hepatic glucose production. Furthermore, unlike insulin-mediated suppression of hepatic glucose production, incubation of hepatocytes with the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor Ly294002 had no effect on the ability of naringenin to suppress hepatic glucose production. Further, naringenin did not increase phosphorylation of Akt at Ser473 or, Thr308, indicating this down-stream target of PI3-kinase is also not a player in naringenin-mediated suppression of hepatic glucose production. Importantly, like the dimethylbiguanide, metformin, naringenin significantly decreased cellular ATP levels without increasing cell cytotoxicity. Together, these results suggest that the aglycone, naringenin, has a role in the attenuation of hyperglycemia and may exert this effect in a manner similar to the drug, metformin.
Insulin and insulin-like growth factor signalling in neoplasia.
Nat Rev Cancer. 2008 Dec; 8(12): 915-28
Pollak M
Insulin and insulin-like growth factors (IGFs) are well known as key regulators of energy metabolism and growth. There is now considerable evidence that these hormones and the signal transduction networks they regulate have important roles in neoplasia. Epidermiological, clinical and laboratory research methods are being used to investigate novel cancer prevention and treatment strategies related to insulin and IGF signalling. Pharmacological strategies under study include the use of novel receptor-specific antibodies, receptor kinase inhibitors and AMP-activated protein kinase activators such as metformin. There is evidence that insulin and IGF signalling may also be relevant to dietary and lifestyle factors that influence cancer risk and cancer prognosis. Recent results are encouraging and have justified the expansion of many translational research programmes.
Management of type 2 diabetes in patients with heart failure.
Curr Treat Options Cardiovasc Med. 2008 Dec; 10(6): 465-75
Aguilar D
Diabetes mellitus and heart failure (HF) commonly coexist, and together these conditions are associated with increased morbidity and mortality compared with either condition alone. Although the optimal treatment strategy to achieve glucose control in HF patients with type 2 diabetes has not been well studied, given the common coexistence of these conditions and the need to adequately treat hyperglycemia to prevent microvascular complications, it is important for clinicians to understand the potential implications of diabetic therapy in patients with established HF. Until recently, metformin was contraindicated in patients with HF because of the potential risk of lactic acidosis; however, recent retrospective studies of metformin use in HF patients have shown that this medication may be used safely and indeed may be beneficial in patients with stable HF. The association between thiazolidinediones (TZDs) and HF remains controversial, but recent prospective randomized trials of TZD use in HF patients suggest that worsening volume retention associated with these agents may lead to worsening of HF symptoms. The recently developed incretin-based therapies, such as exenatide and sitagliptin, also have not been extensively studied in HF populations; however, small pilot studies of glucagon-like peptide-1 have shown potential promise in the treatment of diabetic patients with HF. Although they may be difficult to perform, future randomized controlled trials are needed to establish optimal treatment goals and strategies in this population.
[Impact of overweight on the outcome of ovarian stimulation]
Bull Acad Natl Med. 2008 Apr; 192(4): 661-70; discussion 670-1
Hugues JN
Overweight and obesity have a negative impact on the efficacy of agents used to induce ovulation, and especially on the dose of clomiphene citrate or gonadotrophins required to achieve ovulation. BMI is a major predictor of the ovarian response. In IVF-ICSI cycles, overweight is associated with a decrease in the number of oocytes. While the pregnancy rate is not dependent on weight, the risk of early miscarriage is increased in obese women. Therefore, overweight should be managed before ovarian stimulation begins. The efficacy of insulin-sensitizing agents such as metformin is not fully clear, but their combination with clomiphene citrate or FSH seems promising.