Obviously it is not possible to comment on your plant extract because of lack of detailed information, as to how it works but in case of metformin, it does reduce hepatic glucose production, in vivo.

http://diabetes.diabetesjournals.org/content/51/1/139.short

Does your high fat diet contain high glucose/carbohydrate as well?

Is there any possibility that your blood glucose measurements may be inaccurate?  22mM is not high enough to become difficult to measure even with a portable glucometer designed for home use. The other potential issue may be animal handling experience. Sprague-Dawley rats tend to be more inherently more "unfriendly" than Wistar or Lewis strains of rats. If you are getting them a little excited while trying to draw the blood, you will raise their blood glucose levels.

Thank you so Tausif.

The composition of HFD was 35% CHO, 45% fat and 20% protein and the period of feeding was 8 weeks. Bood glucose is measuring weekly by glucometer .  For in vitro test, IC5o of  inhibition of alpha - glucosidase activity was 

In addition to the Dr. Tausif Alam  , at what time you measure the glucose? Is it after overnight fasting? After how many hour you administrate the drug you measure the glucose? Is it in the morning or afternoon you provide the drug? And check also the metformin (250mg/kg BW) if you prepared it from the tablet in the market?     

Thank you Dr. paulos  

  I measure the glucose  after overnight night fasting  12 -10 hours and after 24 h from last drug administration.  I provide the drug in the morning and

I weight the drug again from the tablet. 

Best regards

I presume the extract is being given by oral route, if so, the bioavailability of plant extract at stomach pH may be the issue.  If not absorbed sufficiently from gut in-vitro activity will not match in-vivo.  If you have access to MDCK cell line testing that might be helpful in determining PD/PK of extract. If not solubilized/absorbed well at gut pH that would explain lack of in-vivo activity.

I can't comment on your plant extract but the lack of activity with metformin may be a function of PK.  Metformin has a relatively short half-life, around 4 hours in humans which is one of the reasons it is dosed BID.  In rats, the half-life may be as short as 2 hours:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992897/

The glucose reducing effects of metformin are also short-lived in rats:

http://dmd.aspetjournals.org/content/30/8/861.full

There's no reason you need to dose 5 weeks to see activity of metformin.  Look at blood glucose levels within 2-6 hours after dosing.  If there is no effect, measure plasma levels of metformin at the same time to confirm bioavailability.

Thank you so much Dr. Alan Carter and Dr. Eric Vajda  about worth information.

Hello...

Please try with increased dose of Metformin. I remember Metformin can be dosed 350 to 450mg/kg BW once daily in you mentioned animal model. Hope it will work. I experience the same.

I can not answer about your plant extract. Thank you, Regards

Thank you so much Dr. Chandra

I am using metformin (50 mg/kg b.w.) as a standard for my study. It reduced the glucose levels to near normal in high fructose diet induced insulin resistance animal model. I had given metformin orally. Insulin resistance may get reversed, diabetes may not. Feeding HFD for 28 days will result in insulin resistance more than that period. DIABETES? Try measuring Insulin. Beta cell dysfunction? there may be problem with insulin secretion or insulin binding. Duration of the treatment may depends on many factor.  

Thank you so much for your  worth information