Treating prediabetes with metformin Systematic review and meta-analysis

Primary Healthcare Research Unit, Health Science Centre, 300 Prince Philip Drive, St John's, Newfoundland.
Canadian family physician Medecin de famille canadien (Impact Factor: 1.34). 05/2009; 55(4):363-9.
Source: PubMed


To determine if the use of metformin in people with prediabetes (impaired glucose tolerance or impaired fasting glucose) would prevent or delay the onset of frank type 2 diabetes mellitus.
MEDLINE was searched from January 1966 to the present, and articles meeting the selection criteria were hand searched.
Randomized controlled trials that involved administration of metformin to delay or prevent type 2 diabetes in individuals with impaired glucose tolerance or impaired fasting glucose were included. Development of diabetes was a required outcome measure; follow-up time of at least 6 months was required. Three studies met these criteria.
The 3 studies varied in ethnicity of the population studied, in the rates of conversion to diabetes from prediabetes, and in the dose of metformin used. In general the studies were well done, although 2 of the 3 did not do true intention-to-treat analyses. A sensitivity analysis was completed by converting all data to intention-to-treat data and assuming a worst-case scenario for the people who were lost to follow-up.
Metformin decreases the rate of conversion from prediabetes to diabetes. This was true at higher dosage (850 mg twice daily) and lower dosage (250 mg twice or 3 times daily); in people of varied ethnicity; and even when a sensitivity analysis was applied to the data. The number needed to treat was between 7 and 14 for treatment over a 3-year period.

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    • "According to studies in some cases for prediabetic patients with severe risk factors, prescribing medication may be appropriate especially in those for whom lifestyle therapy is not sustainable and who are at high-risk for developing type-2 diabetes.[11] As mentioned earlier such cases were not eligible to enter the survey. "
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    ABSTRACT: Background: The beneficial effect of using nonacetylated salicylates such as salsalate on decreasing the speed of diabetes progression is a controversial issue. The aim of this study was to evaluate the effect of salsalate on metabolic-syndrome-associated parameters as well as the endothelial function of diabetic and impaired glucose tolerance patients. Materials and Methods: Patients were collected from Isfahan endocrinology research center referrals. Patients with impaired glucose tolerance diagnosis or newly diagnosed diabetes were enrolled in the study. Patients were randomized to receive 1.5 g salsalate (2 × 750 mg) BID or placebo twice a day for 3 months. After the mentioned period, all patients were recalled and complete examination was done; blood samples for biochemistry measurements were drawn (for measuring FBS, post prandial glucose, HbA1C, Total cholesterol, HDL, TG, LDL) and forearm flow-mediated dilation (FMD) was performed. Results: Forty patients were enrolled, 32 patients (80%) were female. Mean age of patients was 47.15 ± 6.67 years. FBS (fasting blood sugar) was shown to be significantly different between intervention and control subjects before or after treatment. FMD increased significantly in the intervention group (P = 0.004). Conclusion: The study showed that salsalate decreased FBS levels of patients. It may also improve endothelial function as FMD increased significantly in the intervention group.
    Journal of research in medical sciences 04/2014; 19(4):287-92. · 0.65 Impact Factor
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    • "Lily and Godwin reported a decreased rate of conversion from pre-diabetes to diabetes in individuals with IGT or IFG in their systematic review and meta-analysis of randomized controlled trials. This effect was seen at both a higher metformin dosage (850 mg twice daily) and lower metformin dosage (250 mg twice or 3 times daily) in people of varied ethnicity [15]. "
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    ABSTRACT: The management of T2DM requires aggressive treatment to achieve glycemic and cardiovascular risk factor goals. In this setting, metformin, an old and widely accepted first line agent, stands out not only for its antiglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution. These properties may have contributed to the decrease adverse cardiovascular outcomes otherwise not attributable to metformin's mere antihyperglycemic effects. Several other classes of oral antidiabetic agents have been recently introduced, introducing the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs. There is increasing evidence from in vivo and in vitro studies supporting its anti-proliferative role in cancer and possibly a neuroprotective effect. Metformin's negligible risk of hypoglycemia in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile. The tolerability of metformin may be improved by using an appropiate dose titration, starting with low doses, so that side-effects can be minimized or by switching to an extended release form. We reviewed the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits beyond its glycemic effect. We also discuss its potential role for a variety of insulin resistant and pre-diabetic states, obesity, metabolic abnormalities associated with HIV disease, gestational diabetes, cancer, and neuroprotection.
    Diabetology and Metabolic Syndrome 02/2013; 5(1):6. DOI:10.1186/1758-5996-5-6 · 2.17 Impact Factor
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    • "In fact, glucose parameters can be improved with physical activity, weight management and healthy diet and thus open doors for lifestyle recommendations and underline their significance [22-24]. Prediabetes can also be effectively treated with Metformin which can decrease the rate of conversion from prediabetes to diabetes [22,25,26]. Approaching persons early in the pathway to diabetes may be much more effective than treating them when diabetes is established. "
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    ABSTRACT: Background Established risk models for the prediction of cardiovascular disease (CVD) include blood pressure, smoking and cholesterol parameters. The use of total cholesterol for CVD risk prediction has been questioned, particularly for primary prevention. We evaluated whether glucose could be used instead of total cholesterol for prediction of fatal CVD using data with long follow-up. Methods We followed-up 6,095 men and women aged ≥16 years who participated 1977-79 in a community based health study and were anonymously linked with the Swiss National Cohort until the end of 2008. During follow-up, 727 participants died of CVD. Based on the ESC SCORE methodology (Weibull regression), we used age, sex, blood pressure, smoking, and fasting glucose or total cholesterol. The mean Brier score (BS), area under the receiver-operating characteristic curve (AUC) and integrated discrimination improvement (IDI) were used for model comparison. We validated our models internally using cross-validation and externally using another data set. Results In our models, the p-value of total cholesterol was 0.046, that of glucose was p < 0.001. The model with glucose had a slightly better predictive capacity (BS: 2216x10-5 vs. 2232x10-5; AUC: 0.9181 vs. 0.9169, IDI: 0.009 with p-value 0.026) and could well discriminate the overall risk of persons with high and low concentrations. The external validation confirmed these findings. Conclusions Our study suggests that instead of total cholesterol glucose can be used in models predicting overall CVD mortality risk.
    Cardiovascular Diabetology 01/2013; 12(1):24. DOI:10.1186/1475-2840-12-24 · 4.02 Impact Factor
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