Receiving Metformin Treatment Research Articles

Does Diabetes Mellitus Abolish the Beneficial Effect of Primary Coronary Angioplasty on Long-term Risk of Reinfarction After Acute ST-Segment Elevation Myocardial Infarction Compared With Fibrinolysis? (A DANAMI-2 Substudy)

Little is known about the effect of diabetes mellitus on long-term clinical outcome after primary percutaneous coronary intervention (pPCI) compared with fibrinolysis in patients who have acute ST-elevation myocardial infarction. We analyzed 3-year clinical outcome in diabetic patients and nondiabetic patients who had been randomized to fibrinolysis or pPCI in the DANAMI-2 trial to compare long-term clinical outcome. The primary end point was a composite of death, clinical reinfarction, or disabling stroke. Median follow-up was 3.8 years. Among 1,572 consecutive patients who had ST-elevation myocardial infarction and were randomized to pPCI or fibrinolysis, 173 (11.0%) had diabetes mellitus; 60 of these patients received metformin treatment and were excluded. After 3 years no difference was found between diabetic patients who underwent pPCI versus fibrinolysis (combined event p=0.37, reinfarction p=0.06 in favor of fibrinolysis), whereas pPCI was superior to fibrinolysis in nondiabetic patients (combined event p=0.002, clinical reinfarction p<0.001). Three-year incidence of clinical reinfarction analyzed with Cox's regression showed that pPCI compared with fibrinolysis increased the relative risk of clinical reinfarction in diabetic patients (relative risk 2.57, 95% confidence interval 1.48 to 4.46, p <0.001) but decreased the risk in nondiabetic patients (relative risk 0.52, 95% confidence interval 0.36 to 0.74, p<0.001). In conclusion, from the DANAMI-2 trial we hypothesize that diabetes may abolish the beneficial effect of pPCI on long-term risk of clinical reinfarction.

Vitamin B12 status of patients treated with metformin: a cross-sectional cohort study

Aim To assess the vitamin B12 status of patients with type 2diabetes who had been receiving metformin treatment for at least one year. Methods Patients with type 2 diabetes attending a diabetes clinic were included in a cross-sectional cohort study. Patients exposed to metformin for more than one year (n=53) were compared with a non-exposed control group (n=31). Serum cobalamin and other variables reflecting vitamin B12 status were measured. Results Patients on metformin had lower cobalamin (289±137 vs. 395±162 pmol/L; p&lt;0.01) and holotranscobalamin (76±49 vs. 97±41 pmol/L; p&lt;0.05), and higher HCy (11.3+3.3 vs. 10.3±2.3 µmol/L; p&lt;0.05); these changes were correlated. Eight metformin patients, but no controls, had holotranscobalamin below the normal range (p&lt;0.05). Methylmalonic acid and folate were similar in both groups. Conclusion Patients exposed to long-term metformin therapy had 26.7% lower cobalamin, 21.6% lower holotranscobalamin and 9.7% higher HCy serum concentrations than control subjects. Such changes indicate a potential risk for development of vitamin B12 deficiency. Our results highlight the necessity of checking B12 status during metformin therapy.

Effects of Metformin on the Uterine and Ovarian Stromal Blood Flow in Women with Polycystic Ovary Syndrome

Objective: To investigate the influence of metformin on the uterine and ovarian stromal blood flow in women with polycystic ovary syndrome (PCOS). Material(s) and Method(s): Thirty-six infertile patients with PCOS were included initially. These patients received metformin treatment for three months with a dosage of 500 mg three times daily. During the period of this study, 13 patients dropped out of the study. Finally, 23 cases had undertaken blood flow assessment of bilateral uterine and ovarian stromal arteries before and after 3-month treatment by the conventional transvaginal color Doppler ultrasonography. The pulsatility index (P1) and resistance index (RI) of the bilateral uterine and ovarian stromal arteries were measured. The data before treatment were compared with the ones after treatment. Among them, the pregnant patients were further identified and received another analysis to compare the changes after metformin treatment. Result(s): When comparing the vascular impedance of all the patients before and after metformin treatment, the P1 and RI of the bilateral uterine and ovarian stromal arteries showed no significant differences. In addition, in the seven patients (30.4%) who were pregnant, the vascular impedance of these pregnancy women did not have significant differences while compared with that of these non-pregnancy women who also received metformin treatment. Conclusion(s): Although some previous studies reported that metformin might improve regional blood flow, no significant changes in the vascular impedance of uterine and ovarian flow after metformin treatment can be observed in this study. Besides, no differences in the P1 or RI of the uterine and ovarian arteries were found in the pregnant women after treatment, which implies that metformin may not ameliorate blood flow indexes in PCOS women. However, the underlying effect of metformin to PCOS remains to be solved and further studies are needed.

Cardioprotection by metformin is abolished by a nitric oxide synthase inhibitor in ischemic rabbit hearts.

We investigated the effects of metformin on myocardial metabolism during ischemia by 31P-nuclear magnetic resonance (NMR) in isolated rabbit hearts. Metformin was administered 60 min prior to induction of global ischemia, or in combination with a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), at 5 min or 60 min prior to the ischemia. Normothermic global ischemia was then carried out for 45 min. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each: a control (C) group; an M group receiving metformin treatment alone; an M+L (5) group receiving metformin treatment with L-NAME at 5 min before ischemia; and an M+L (60) group receiving metformin treatment with L-NAME at 60 min before ischemia. During ischemia, the decrease in adenosine triphosphate (ATP) was significantly inhibited in the M group in comparison with the C group (p < 0.01). However, this preservation of ATP in the M group was inhibited in the M+L (5) group during ischemia. In contrast, in the M+L (60) group, this preservation of ATP in the M group was not inhibited during, but not at the end of, ischemia. These results suggest that metformin has a significant beneficial effect for improving the myocardial energy metabolism during myocardial ischemia. This cardioprotection may be more dependent on nitric oxide synthase during ischemia than during pre-ischemia.