Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new metformin research articles will be listed here shortly after becoming available to us.
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Medical research on metformin
HIV-associated lipodystrophy: a review of underlying mechanisms and therapeutic options.
J Antimicrob Chemother. 2008 Jun 18;
Mallewa JE, Wilkins E, Vilar J, Mallewa M, Doran D, Back D, Pirmohamed M
Lipodystrophy (LD) is a common adverse effect of HIV treatment with highly active antiretroviral therapy, which comprises morphological and metabolic changes. The underlying mechanisms for LD are thought to be due to mitochondrial toxicity and insulin resistance, which results from derangements in levels of adipose tissue-derived proteins (adipocytokines) that are actively involved in energy homeostasis. Several management strategies for combating this syndrome are available, but they all have limitations. They include: switching from thymidine analogues to tenofovir or abacavir in lipoatrophy, or switching from protease inhibitors associated with hyperlipidaemia to a protease-sparing option; injection into the face with either biodegradable fillers such as poly-l-lactic acid and hyaluronic acid (a temporary measure requiring re-treatment) or permanent fillers such as bio-alcamid (with the risk of foreign body reaction or granuloma formation); and structured treatment interruption with the risk of loss of virological control and disease progression. There is therefore a need to explore alternative therapeutic options. Some new approaches including adipocytokines, uridine supplementation, glitazones, growth hormone (or growth hormone-releasing hormone analogues), metformin and statins (used alone or in combination) merit further investigation.
Fertil Steril. 2008 Jun 17;
Luque-Ramírez M, Mendieta-Azcona C, Alvarez-Blasco F, Escobar-Morreale HF
OBJECTIVE: To compare the effects of metformin versus an antiandrogenic contraceptive pill on ambulatory blood pressure monitoring (ABPM) and carotid intima media thickness (CIMT) in women with polycystic ovary syndrome (PCOS). DESIGN: Clinical randomized trial. SETTING: Academic hospital. PATIENT(S): Thirty-four consecutive PCOS patients. INTERVENTION(S): PCOS patients randomized to oral treatment with metformin (n = 19) or with Diane(35) Diario pill (n = 15) for 24 weeks. MAIN OUTCOME MEASURE(S): ABPM recordings and ultrasound measurements of CIMT as marker of subclinical atherosclerosis obtained at baseline and after treatment. RESULT(S): Metformin resulted in reductions in daytime and 24-hour average systolic and diastolic blood pressure whereas Diane(35) Diario induced a slight increase in these parameters. Compared with a nonhyperandrogenic control group, the increased CIMT values of PCOS patients decreased to the normal range after treatment with either metformin or Diane(35) Diario. CONCLUSION(S): Metformin treatment decreased daytime ABPM recordings whereas Diane(35) Diario exerted the opposite effect. The safer blood pressure profile of metformin should be considered in PCOS patients who present with a history of hypertension or who are at risk for this disorder. Treatment with either Diane(35) Diario or metformin improved CIMT mean values.
Int J Clin Pract. 2008 Jun 19;
Preiss D, Sattar N, Harborne L, Norman J, Fleming R
Context: The prevalence of non-alcoholic fatty liver disease (NAFLD) in polycystic ovarian syndrome (PCOS) is high. Small studies have shown reductions in serum alanine aminotransaminase (ALT) and gamma-glutamyltransaminase (GGT) concentrations, both surrogate liver fat markers, and sometimes improvements in liver histology in individuals with NAFLD treated with metformin. Aims: We investigated whether metformin reduces serum ALT and GGT concentrations in obese women with PCOS. Methods: We performed post hoc data analysis from a trial, involving 82 obese women aged 22-46 years with PCOS, conducted at an academic institution. Participants were treated with metformin 1500 or 2550 mg/day for 8 months. Anthropometric measurements and blood samples (serum ALT, GGT, lipids, leptin, C-reactive protein, insulin, glucose analyses) were taken at baseline, 4 and 8 months. Results: Sixty-six participants completed the study. Mean weight, serum ALT and GGT decreased from 100.3 to 96.6 kg (p < 0.0001), 29.7 to 25.8 U/l (p = 0.012) and 21.4 to 16.9 U/l (p < 0.0001) respectively. Associations between weight reduction and decreases in serum ALT and GGT were highly significant and independent of change in Homeostasis Model Assessment of Insulin Resistance. In women with baseline ALT > 29.7 U/l (median), ALT reduction was highly significant (p = 0.005); however in those with baseline ALT < 29.7 U/l, ALT did not change despite similar weight reduction. There was no difference in reductions in ALT and GGT when the two metformin doses were compared. Intention-to-treat analyses gave comparable results. Conclusions: Metformin therapy is associated with reductions in surrogate liver fat markers in obese women with PCOS. This adds indirect support for a benefit of metformin in attenuating/reversing liver fat accumulation in PCOS and more generally.
Current treatment of non-alcoholic fatty liver disease.
Diabetes Obes Metab. 2008 Jun 16;
Ahmed MH, Byrne CD
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in Western World and frequently associated with insulin resistance and overweight and occurs often with type 2 diabetes. Interestingly, NAFLD is not only regarded as a hepatic component of the metabolic syndrome but also as an independent risk factor and a marker for increase in cardiovascular disease (CVD). Significantly, NAFLD is associated with an increased risk of all-cause mortality and predicts future CVD events independent of age, sex, LDL-cholesterol and features of metabolic syndrome. Although there was initial concern about drug toxicity with NAFLD, increasing evidence suggests that commonly used drugs such as metformin and statins do not cause harm and the thiazolidinediones (TZDs) may even confer a therapeutic benefit in NAFLD. Interestingly, medical and surgical treatments of obesity show potential benefit in treating NAFLD. In this review, we have focused on the safety and therapeutic impact of TZDs, statins, metformins and obesity medications in NAFLD. The potential benefit of bariatric surgery and the role of weight loss per se in treating NAFLD are also discussed.
Rev Med Liege. 2008 Mar; 63(3): 158-65
Scheen AJ, Van Gaal LF
Exenatide (Byetta) is a synthetic derivative of exendin-4 and an agonist of receptors of glucagon-like peptide-1 (GLP-1). It is resistant to the rapid inactivation by dipeptidylpeptidase-4 and acts as an incretin mimetic. It stimulates insulin secretion by the B cell in a glucose-dependent manner whereas it inhibits glucagon secretion. Exenatide improves mainly postprandial glucose concentrations and lowers glycated haemoglobin (HbA(1c)) levels, without being directly responsible for hypoglycaemia or requiring mandatory home blood glucose monitoring. Furthermore, it slows down gastric emptying and promotes sustained body weight reduction, even in absence of frequently reported nausea following treatment initiation. Exenatide is recommended and reimbursed in Belgium for the treatment of type 2 diabetes, in combination with metformin and a sulfonylurea, in patients not adequately controlled with maximal tolerated doses of these oral glucose-lowering agents. Exenatide is presented as pre-filled pens for subcutaneous injection. The recommended initial dose is 5 microg before morning and evening meals, to be up titrated to 10 microg twice daily. Exenatide may represent a valuable alternative to insulin therapy, especially in overweight or obese patients with type 2 diabetes and not ready to perform home blood glucose monitoring.
Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin.
Vasc Health Risk Manag. 2008; 4(2): 383-94
Ahrén B
Inhibition of dipeptidyl peptidase-4 (DPP-4) as a novel therapy for type 2 diabetes is based on prevention of the inactivation process of bioactive peptides, the most important in the context of treatment of diabetes of which is glucagon-like peptide-1 (GLP-1). Most clinical experience with DPP-4 inhibition is based on vildagliptin (GalvusR, Novartis) and sitagliptin (JanuviaR, Merck). These compounds improve glycemic control both in monotherapy and in combination with other oral hyperglycemic agents. Both have also been shown to efficiently improve glycemic control when added to ongoing metformin therapy in patients with inadequate glycemic control. Under that condition, they reduce HbA1C levels by 0.65%-1.1% (baseline HbA1C 7.2-8.7%) in studies up to 52 weeks of duration in combination versus continuous therapy with metformin alone. Sitagliptin has also been examined in initial combination therapy with metformin have; HbA1 was reduced by this combination by 2.1% (baseline HbA1C 8.8%) after 24 weeks of treatment. Both fasting and prandial glucose are reduced by DPP-4 inhibition in combination with metformin in association with improvement of insulin secretion and insulin resistance and increase in concentrations of active GLP-1. The combination of DPP-4 inhibition and metformin has been shown to be highly tolerable with very low risk of hypoglycemia. Hence, DPP-4 inhibition in combination with metformin is an efficient, safe and tolerable combination therapy for type 2 diabetes.
[Acidosis lactic by metformin.]
An Med Interna. 2008 Mar; 25(3): 153-4
Marchena Yglesias PJ, García González I, Rico Villoria N, Castellanos Llauger P, Ricart Conesa A
Endocr Pract. 2008 May-Jun; 14(4): 511-3
Miranda-Garduño LM, Gómez-Pérez FJ, Rull JA
J Pediatr Endocrinol Metab. 2008 Apr; 21(4): 339-48
Atabek ME, Pirgon O
AIM: To determine whether metformin treatment for 6 months is effective in reducing body weight and hyperinsulinemia and also ameliorating insulin sensitivity indices in obese adolescents with hyperinsulinemia. METHODS: One hundred and twenty adolescents (age range 9-17 years) with BMI >95th percentile for age and sex were included (metformin group, n = 90 [45 females, 45 males]; placebo group, n = 30 [15 females, 15 males]). The groups received 500 mg metformin (n = 90) or placebo (n = 30) twice daily for 6 months, plus individually tailored diet, exercise and behavioral therapy. Hyperinsulinism and insulin sensitivity indices were defined from fasting samples. Oral glucose tolerance tests were performed before and after treatment. RESULTS: Before treatment, there were no significant differences between the metformin group and control group in terms of anthropometric data and metabolic parameters. After metformin, there was a significant decline in body mass index (from 28.5 +/- 3.4 to 26.7 +/- 4 kg/m2, p < 0.001), fasting insulin (from 19.2 +/- 10.4 to 11.1 +/- 6.1 microU/ml, p < 0.001) and 120 min insulin levels (from 103.7 +/- 73.8 to 49.8 +/- 30.9 microU/ml, p < 0.001). FGIR increased significantly from 6.26 +/- 3.0 to 12.5 +/- 10.6 (p < 0.001) and HOMA-IR was reduced from 4.95 +/- 3.34 to 2.6 +/- 1.6 (p < 0.001) after treatment. QUICKI significantly increased from 031 +/- 0.02 to 034 +/- 0.03 (p < 0.001) in the metformin group. Moreover, in comparison of changes in insulin sensitivity indices between the metformin treated and control groups, the metformin treated group showed significantly improved metabolic control at the end of the study. CONCLUSION: These data suggest that metformin treatment is effective in reducing insulin resistance and also ameliorating metabolic complications of insulin resistance syndrome in obese adolescents with hyperinsulinemia.
Clin Ther. 2008 May; 30(5): 858-67
Schwartz SL, Ratner RE, Kim DD, Qu Y, Fechner LL, Lenox SM, Holcombe JH
Objective: The aim of this study was to examine the glucose-lowering effect of exenatide over 24 hours in patients with type 2 diabetes with inadequate glycemic control using metformin, with or without a thiazolidinedione (TZD). Methods: This randomized, double-blind, 2-arm, parallel-group, placebo-controlled, 2-week study was conducted in patients with type 2 diabetes with inadequate glycemic control, despite metformin with or without a TZD. Patients underwent a baseline and a week-2 (study end) 24-hour admission during which serial serum glucose measurements were taken. Preprandial and postprandial concentrations of triglycerides and free fatty acids were also measured. Meals provided for each patient were identical at the baseline and week-2 assessments. Following the baseline admission, patients were randomized to receive SC injections of either exenatide (5 mug BID for 1 week, then 10 mug BID for the next week) or placebo (volume equivalent) for 14 days. Results: A total of 30 patients (19 women [63%], 11 men [37%]; mean [SD] age, 52.6 [11.2] years; weight, 94.3 [23.0] kg; body mass index, 34.2 [6.1] kg/m(2); glycosylated hemoglobin value, 8.0% [0.9%]; diabetes duration, 8.7 [5.6] years; race, Hispanic 18 [60%], white 10 [33%], black 2 [7%]) were eligible. Seventeen patients (57%) were randomized to treatment with exenatide and 13 patients (43%) received placebo. Concurrent antidiabetic medications were metformin only (n = 19 [63%]) and metformin plus a TZD (n = 11 [37%]). All postbaseline values were least squares mean (SE). After 2 weeks (study end), the 24-hour time-average glucose values were 7.0 (0.2) and 8.8 (0.3) mmol/L for exenatide-treated and placeboadministered patients, respectively (P < 0.001). The glucose values for patients treated with exenatide were lower compared with those in patients who received placebo 2 hours after the morning meal (6.6 [0.4] vs 12.0 [0.5] mmol/L; P < 0.001), the midday meal (8.8 [0.5] vs 11.8 [0.6] mmol/L; P = 0.001), and the evening meal (6.8 [0.4] vs 11.3 [0.4] mmol/L; P < 0.001). The mean durations of patient exposure to glucose concentrations >7.8 and >11.1 mmol/L were significantly shorter for the exenatide group compared with the placebo group (>7.8 mmol/L: 6.8 [0.9] vs 14.1 [1.1] hours; >11.1 mmol/L: 1.0 [0.7] vs 4.7 [0.8] hours; both, P < 0.001). After 2 weeks, the postprandial triglyceride excursions after the morning and evening meals for patients treated with exenatide were significantly lower compared with those treated with placebo. There was no apparent effect on free fatty acid concentrations. Conclusions: In these patients with type 2 diabetes, exenatide was associated with significantly reduced glucose concentrations at multiple time points during 24 hours, with the greatest effect seen on postprandial glucose concentrations. In addition, exenatide was associated with decreased overall hyperglycemic exposure and significantly decreased postprandial triglyceride excursions. These results are consistent with those seen in other studies that reported the effectiveness of exenatide in controlling hyperglycemia in patients with type 2 diabetes.