6 months ago this column reported  Bahani  ea’s  Surrey University open study showing  that in gestational diabetes GDM,  with metformin up to 2500mg/day, “Neonatal morbidity was improved in the metformin group p<0.01:  prematurity (0 vs. 10%), neonatal jaundice (8 vs. 30% ) and admission to neonatal unit (6 vs. 19%)”; and   “It is just a year since Glueck ea in Cincinnati showed that adding metformin to tolerance to sensible diet in women with PCOS  before conception greatly improved both conception rate, successful pregnancy and lowered gestational diabetes rate from 30% to 12%.”
Now the third RCT of metformin in GDM has just been reported, bringing to 963 the number of diabetic pregnancies treated prospectively in randomized controlled trials RCTs of metformin vs other antidiabetics.
METFORMIN vs INSULIN: In 2007 Rowan ea from New Zealand reported 751 GDM cases treated in an open prospective randomized controlled trial RCT  from a mean of 30weeks pregnancy and a mean BMI  of 32kg  with a median of 2500mg metformin a day OR insulin. Maternal or foetal complication outcomes were identical 32% on the two drugs.  More women stated  they would choose to receive metformin treatment again (76.6% vs. insulin 27%, P<0.001). Only 46% of the women allocated initially to metformin eventually required also some insulin”.       And Lisa Moore ea at the University New Mexico similarly randomized 63 pregnant women with GD to metformin or insulin ; ” metformin appears to be an effective alternative to insulin in the treatment of GDM”.

METFORMIN vs GLYBURIDE: Now the same Lisa Moore Albuquerque team reports similar RCT comparison of metformin with glyburide in 149 GDM  cases with BMI about 32kg, height about 1.585m  treated from about week 28 with 500mg up to 2000mg metformin  or glyburide. They found that “In the patients who achieved adequate glycemic control, the mean fasting and 2-hour postprandial blood glucose levels were not statistically different between the two groups. However, 26 patients in the metformin group (34.7%) and 12 patients in the glyburide group (16.2%) did not achieve adequate glycemic control and required insulin therapy (P=.01).
However,  with hindsight  in the 2nd Moore trial,  the starting dose of metformin was too high- 500mg/d- so that one patient fell out of the trial immediately because of intolerance to metformin (25% fell out of the USA DPP trial early  for similar reason) ; and  the ceiling dose of metformin was only 2000mg/d, when renal clearance- glomerular filtration rate- is increased  about 50% in pregnancy, and tolerance of metformin may be genetically so good that some tolerate 3g/day well.
If these physiological principles are followed as we normally do in practice- where the median dose of metformin is 2500mg/d as used in the far bigger New Zealand trial, then the results on metformin compared to glyburide may be expected to be  much better. One of the many problems of pregnancy is constipation which again will improve metformin tolerance in this regard.
Charles Glueck’s team in Cincinnatti has shown in  many studies (2002 et seq) the past decade how metformin 2550mg/day reverses the weight gain preceding metabolic syndrome, and reverses the infertility of PCOS polycystic ovary syndrome to the extent that it almost eliminates gestational diabetes and normalizes fertility, conception, pregnancy success and outcomes in such women and their infants .
These facts confirm why the centuries-old antidiabetic galega officinalis  derivative dimethylguanidine metformin (1922) is the best chronic multisystemic- beneficial drug ever discovered, like so many other natural drugs like  marine omega3,  hormones, the ~16  (co)vitamins including coQ10,  minerals including lithium,  other human biologicals like arginine carnitine Nacetylcysteine alphalipoic acid and carnosine, and plant (extracts)  like reserpine, huperzine A , garlic, stevia and catsclaw,   are  better chronic preventative drugs than every single designer synthetic chronic drug developed by modern science.
It is now inexcusable, unethical to delay initiating, at any age from children to the old, permanent metformin  slowly up  to comfortable tolerance in anyone who cannot with reasonable diet and lifestyle prevent increasing overweight or waist girth, let alone with prediabetes, diabetes of either type, gestational diabetes, PCOS, or cancer.
12 Jan 2009: Dr Charles Glueck from frozen Cincinnati sums it up: “The crucial issue here is dose. Our data suggests that optimum outcomes come with 2.5 g, with subjects slowly titrated up to that dose. There is also a very big difference between treatment of already established GD, when the pancreatic insulin reserve is already overwhelmed, and PREVENTING GD by reducing insulin resistance. Metformin may well be a better drug in prevention of GD than in treatment, but without optimal dosing, the question of treatment remains unresolved. We are looking into a RCT of this issue”. CJG

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