Metformin's Effects on Glucose and Lipid Metabolism in Patients with Secondary Failure to Sulfonylureas

Fanghänel, Guillermo; Sánchez‐Reyes, Leticia; Trujillo, C; Sotres, David; Espinosa-Campos, Jorge

doi:10.2337/diacare.19.11.1185

Cited by 49 publications

(32 citation statements)

References 25 publications

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“…Significant reduction of HbA 1C (-0.79 ± 1.18%) was observed after 6 months administration of metformin. While an improvement of lipid metabolism in European and American populations has been reported [2,6,13,14], no such improvement has been reported in a Japanese one [4,5]. This may be attributable to the difference in the setting of the therapeutic dosage, BMI, insulin secretion capacity, and 'thrifty' genetic factors between Japanese and American / European populations.…”

Section: Discussionmentioning

confidence: 64%

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Clinical Characteristics Influencing the Effectiveness of Metformin on Japanese Type 2 Diabetes Receiving Sulfonylureas

et al. 2007

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Abstract. In this study, we described the effectiveness of metformin on Japanese type 2 diabetes patients receiving sulfonylureas and the clinical characteristics of the patients whose glycemic control were significantly improved with metformin administration. Our results showed that the reduction of glycohemoglobin (HbA 1C ), serum concentration of total cholesterol, and diastolic blood pressure was statistically significant through the administration of metformin. The clinical characteristics of the patients who responded to metformin therapy exhibited lower systolic blood pressure in addition to higher HbA 1C value just before administration of metformin when compared with ∆HbA 1C (HbA 1C 6 months after administration of metformin -HbA 1C before administration of metformin). Moreover, effectiveness of metformin was weakened, in comparison with non-hypertensive patients, even though the blood pressure of hypertensive patients was reduced to normal range by medication with antihypertensive drugs. But average reduction of HbA 1C level of hypertensive patients without antihypertensive medications was smaller than those of patients with high blood pressure with such medication. These results suggested that high blood pressure and hypertension phenotype itself were suppressive factors of metformin but antihypertensive therapy itself enhanced the effectiveness of metformin regardless of the improvement of blood pressure.

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Section: Discussionmentioning

confidence: 64%

“…Reports on the improvement of blood pressure have been published by Landin et al [13] and Fanghanel et al [14] and a significant reduction in SBP and DBP was also observed. Meanwhile, no weight change was observed during these studies.…”

Section: Discussionmentioning

confidence: 82%

Clinical Characteristics Influencing the Effectiveness of Metformin on Japanese Type 2 Diabetes Receiving Sulfonylureas

et al. 2007

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“…8 Metformin improves insulin sensitivity, decreases insulin levels, and controls hyperglycemia. 10,11 In addition, metformin improves lipid profiles and lowers blood pressure in both patients and animal models with impaired glucose tolerance and type 2 diabetes mellitus. [11][12][13][14] In addition to its insulin-sensitizing effects, metformin has also been shown to have direct vascular effects.…”

mentioning

confidence: 99%

“…10,11 In addition, metformin improves lipid profiles and lowers blood pressure in both patients and animal models with impaired glucose tolerance and type 2 diabetes mellitus. [11][12][13][14] In addition to its insulin-sensitizing effects, metformin has also been shown to have direct vascular effects. 15,16 Thus, it is currently unclear whether the hypotensive effect of metformin is due to a direct vascular effect, its ability to improve insulin sensitivity, its ability to improve lipids, or a combination of mechanisms.…”

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confidence: 99%

Metformin Improves Vascular Function in Insulin-Resistant Rats

et al. 2000

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Abstract-This study assessed the effect of metformin treatment on insulin, mean arterial pressure (MAP), and endothelial function in insulin-resistant (IR) rats. In addition, we assessed the direct effect of metformin in vitro. Sprague-Dawley rats were randomized to control (nϭ28) or IR (nϭ28) groups. Rats were further randomized to receive metformin (300 mg/kg) or placebo for 2 weeks. MAP and insulin were measured. Subsequently, a third-order branch of the superior mesenteric artery was isolated, and endothelial function was assessed. Specifically, dose-response experiments of acetylcholine (ACh) with or without N-nitro-L-arginine (LNNA) were performed. For in vitro experiments, mesenteric arteries were removed from untreated control and IR rats and treated with metformin (100 mol/L) before AChϮLNNA. MAP and insulin levels were improved in IR-metformin compared with IR-placebo rats. Maximal relaxation (E max ) to ACh was enhanced in IR-metformin (92Ϯ2%) compared with IR-placebo rats (44Ϯ4%) (PϽ0.05). Relaxation in response to AChϩLNNA was greater in IR-metformin (33Ϯ4%) than in IR-placebo rats (12Ϯ4%) but remained depressed compared with control rats (E max ϭ68Ϯ5%). The control group was not affected by metformin. In vitro treatment of arteries with metformin in response to ACh produced results similar to those in the experiments with metformin-treated rats. Although metformin improves metabolic abnormality in IR rats, this action does not appear to mediate its effect on vascular function. Both in vivo and in vitro metformin improved ACh-induced relaxation in IR rats to control levels, apparently through nitric oxide-dependent relaxation. These data suggest that metformin improves vascular function through a direct mechanism rather than by improving metabolic abnormalities. Key Words: insulin resistance Ⅲ relaxation Ⅲ metformin Ⅲ nitric oxide Ⅲ blood pressure E xcess cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus) is not explained by the presence of traditional cardiovascular risk factors. 1,2 In addition, glucose control with traditional agents, such as sulfonylureas or insulin, does not alter the risk of macrovascular complications. 3 Epidemiological and observational studies suggest that insulin resistance (IR) may play a role in the development of vascular disease in type 2 diabetes mellitus. 4 -6 Moreover, a recent study has shown that treatment of obese type 2 diabetes mellitus patients with metformin, an insulinsensitizing agent, improves cardiovascular sequelae. 7 Taken together, these data suggest that IR is an important risk factor for the development of cardiovascular disease. Unfortunately, the underlying mechanism(s) by which IR promotes vascular disease remains unknown. Previous data from our laboratory and others suggest endothelial dysfunction as a possible mechanism linking IR to vascular disease. 8,9 Specifically, we have shown that endothelium-dependent relaxation is impaired in IR rats because of a defect in nitric o...

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“…One logical explanation for this large effect is that metformin does more than lower blood glucose. A prospective study noted favourable changes in lipids as well as in blood pressure 20 . The large risk reduction associated with MI makes the use of metformin economical.…”

Section: Metforminmentioning

confidence: 99%

Cardiovascular risk reduction in diabetes: underemphasised and overdue. Messages from major trials

Adler

2001

Clinical Medicine

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Diabetes markedly increases the risk of coronary artery disease and death, but is underrecognised as a cardiovascular risk factor, despite the existence of effective treatments. Because patients with diabetes are at high risk for coronary disease, they have more to gain from prevention. There is evidence from clinical trials that select cardiovascular therapies may work better in diabetes, beyond their expected benefit, and may prevent diabetes itself.Diabetes more than doubles the risk of heart disease 1 . This increase is made more serious by figures showing that cardiovascular disease is already the most common cause of death in the general population. In the UK, 35% of all deaths are attributable to cardiovascular disease 2 ; in people with type 2 diabetes this figure reaches almost 60% 3 . Myocardial infarction (MI) is the most common and the most costly complication in diabetes, as well as the number one cause of death. Despite this, doctors and patients apparently do not perceive diabetes to be a major risk for cardiovascular disease. Trials have identified a number of effective means of reducing cardiovascular complications in patients with diabetes. This article will highlight differences between diabetes and other known cardiovascular risk factors and, using examples from large trials, discuss why interventions: may be more important in diabetes work better in diabetes work beyond their expected benefit may prevent diabetes itself. Differences between diabetes and other risk factorsThere are several differences between diabetes and other well-acknowledged risk factors for cardiovascular disease, but perhaps the most important is the lack of prominence and import accorded to diabetes. The under-recognition of diabetes was admitted in 1997 by officials from the US National Institutes of Health who convened a special emphasis panel on the prevention and treatment of cardio- As further evidence, patients with diabetes appear less likely to receive cardiovascular prevention. Aspirin reduces the risk for cardiovascular events in patients with diabetes, hypertension and coronary artery disease to a degree equivalent to other hypertensive patients 5 , but rates of aspirin use for cardiovascular prophylaxis are poor. US national survey data show that only 32% of individuals with both diabetes and cardiovascular disease take aspirin 6 . Diabetic patients admitted for suspected MI are less likely to receive treatment with thrombolysis and aspirin 7 , while diabetic patients discharged following MI are less likely to receive aspirin 8 .Diabetes and cardiovascular disease have been shown to be equivalent in terms of the risk increase for MI 9 . However, among over 15,000 patients enrolled in the MRC/BHF HPS only 7% of those with diabetes but without coronary artery disease reported taking aspirin compared to 77% of patients with coronary artery disease 10 (see end of text for explanation of trials). Aspirin trials for primary prevention in diabetes have not been performed, but there is no obvious reason to believe ...

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Metformin's Effects on Glucose and Lipid Metabolism in Patients with Secondary Failure to Sulfonylureas

Cited by 49 publications

References 25 publications

Clinical Characteristics Influencing the Effectiveness of Metformin on Japanese Type 2 Diabetes Receiving Sulfonylureas

Clinical Characteristics Influencing the Effectiveness of Metformin on Japanese Type 2 Diabetes Receiving Sulfonylureas

Metformin Improves Vascular Function in Insulin-Resistant Rats

Cardiovascular risk reduction in diabetes: underemphasised and overdue. Messages from major trials

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