The UK Prospective Diabetes Study concluded that metformin (Glucophage) was as effective as sulfonylureas in obese patients with type 2 diabetes but might be preferable, because it was associated with less weight gain and fewer hypoglycemic episodes. Now for the first time evidence has shown that metformin is as effective, and possibly even more effective, in diabetic patients who are not obese.
“This study provides evidence-based data to support metformin use in nonobese individuals who have type 2 diabetes,” Cynthia R. Ong, MD, of the Royal Prince Alfred Hospital, Sydney, Australia, and colleagues write in (2006; 29:2361-2364).
This analysis of a large database of Australian patients included 644 adults with type 2 diabetes who had been treated with metformin or sulfonylurea monotherapy for a period ranging from 1 to 4 years before they were switched to dual oral therapy. When they first started taking monotherapy, the median patient age ranged from 51.9 to 61.1 years.
The patients were categorized by body mass index (BMI) into 3 groups: normal (BMI <25 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obese (BMI ≥30 kg/m2). Investigators then compared changes in weight and hemoglobin (Hb) A1c over time, and looked for any associations between diabetes duration and BMI. They also calculated the incidence of diabetes-related macrovascular and microvascular complications according to initial monotherapy type.
During a follow-up of 3.6 to 5.3 years, obese diabetic patients receiving metformin monotherapy lost more weight than obese diabetic patients receiving sulfonylurea monotherapy, while the nonobese patients in the metformin group remained consistently thinner. HbA1c levels did not differ significantly between the groups at any time point.
Obese patients made the switch from monotherapy to dual therapy sooner than normal/overweight patients, regardless of whether they were taking metformin or a sulfonylurea. This suggests that the longer duration of glycemic control with either agent alone in the normal/overweight patients was likely the result of the effects of body weight on the disease process, not to an individual drug.
At the time patients were switched to dual therapy, the nonobese patients in the metformin monotherapy group were taking an average of 2.5 tablets versus 2.8 tablets (all 0.5 g) in the obese group. Thus, “even with a slightly lower dosage, there was a longer duration of successful glycemic control with metformin monotherapy in the two groups of nonobese subjects compared with the obese individuals,” the authors write.
“When the 27 metformin-treated patients with BMI <25 kg/m2 were examined, their median duration of successful monotherapy was longer at 7.0 years, compared with 6.4 years in their sulfonylurea-treated counterparts.” The authors note that this suggests that metformin may be even more effective in patients with type 2 diabetes who are thin.