Mechanism of Action

Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects (except in special circumstances, see PRECAUTIONS) and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.

Pharmacokinetics

Absorption and Bioavailability

Two pharmacokinetic studies have been performed in healthy volunteers to evaluate the bioavailability of RIOMETin comparison with the commercially available metformin tablets under fasting and fed conditions (study 1 and study 2). A third pharmacokinetic study (study 3) assessed effects of food on absorption of RIOMET.

The rate and extent of absorption of RIOMET was found to be comparable to that of Metformin tablets under fasting or fed conditions (see Table 1).

Table 1. Select Mean (±S.D.) Pharmacokinetic Parameters Following Single Oral Doses of 1000 mg RIOMET and Metformin tablets in healthy, nondiabetic adults (n= 36) under fed and fasting conditions

The food-effect study (study 3) assessed the effects of a high fat/high calorie meal and a low fat/low calorie meal on the bioavailability of RIOMET in comparison with administration in the fasted state, in healthy volunteers. The extent of absorption was increased by 21% and 17% with the low fat/low calorie meal and the high fat/high calorie meal, respectively, compared with the administration in the fasted state. The rate and extent of absorption with high fat/high calorie and low fat/ low calorie meal were similar. The mean tmax was 2.5 hours under fasting conditions as compared to 3.9 hours with both low fat/ low calorie meal and high fat/high calorie meals (see Table 2).

Table 2. Select Mean (±S.D.) Metformin Pharmacokinetic Parameters Following Single Oral Doses of 1000 mg RIOMET in healthy, nondiabetic adults (n= 33) under fed (high fat/high calorie meal and low fat/low calorie meal) and fasting conditions (study 3)

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