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Metformin: Beyond Lowering Glucose

“There are actually two things that I would like to take into account in diabetes treatment. One is of course lowering of blood sugar, as manifested by lowering of HbA1c, and, more importantly, reduction of weight of type 2 diabetic patients,” shared Dr. Augusto D. Litonjua, founding president of the Philippine Association for the Study of Overweight and Obesity. “Metformin is probably the only antidiabetic drug that does these two things well.”

According to Dr. Litonjua, metformin’s mechanism of action in lowering blood sugar resides in its ability to phosphorylate and activate the multi-subunit enzyme called adenosine monophosphate-activa. “This enzyme has several benefits, one of which is to suppress gluconeogenesis in the liver, thereby decreasing hepatic glucose production and lowering blood glucose level.”

Dr. Litonjua cited the 1996 study of Bailey and Turner published in the New England Journal of Medicine, which found that 1,000 mg of metformin per day for 3 weeks was associated with a 25 percent decrease in glucose uptake in the muscles, signifying a 25 percent increase in insulin sensitivity. He added that basal hepatic glucose production was also decreased by about 25 percent after the 3-week treatment with 1,000-mg metformin.

Dr. Litonjua also highlighted the importance of weight management in type 2 diabetes, and according to him, metformin is advantageous and unique as it does not cause weight gain, which is common among other antidiabetic drugs. In fact, a meta-analysis of 49 randomized, controlled trials found that metformin is the only antidiabetic drug that can actually lower body weight among patients, in contrast to sulfonylureas and thiazolidinediones.

The study of Strowig and colleagues published in Diabetes Care also found that the addition of metformin to insulin reduced the weight gain caused by the latter from 2.4 to 0.5 kg. “And not only do you achieve a reduction in blood sugar and body weight, but together with that is a 25 percent reduction in insulin requirements—all these due to metformin,” Dr. Litonjua stressed.

Dr. Litonjua further explained that another benefit afforded by metformin is its ability to reduce visceral fat, the most pathologic among body fats, as found by the study of Kurukulasuriya and colleagues published in Diabetes.

“All of these parameters of body weight are reduced with metformin. But we all know that visceral fat is the most of pathologic of all these fat, and we can see that metformin specifically reduces visceral fat.” “The key endocrine defects that are addressed by metformin in the pathophysiology of type 2 diabetes mellitus are not only one but several,” said Dr. Litonjua. “Hyperglycemia in type 2 diabetes is caused by insulin deficiency. Another process in hyperglycemia in type 2 diabetes is insulin resistance of the muscles where the muscles could not take up the glucose in the blood. This in turn is addressed and corrected by metformin.

Lipolysis is increased in type 2 diabetes resulting in increased insulin resistance—this again is reduced by metformin. And its greatest effect is in control of hepatic glycogenolysis, which is responsible for the fasting and postprandial hyperglycemia of type 2 diabetes and this is very well controlled by metformin.”

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