Lifestyle changes and metformin appear most beneficial for pre-diabetes patients at highest risk

Patients at high risk of diabetes widely vary in their likelihood of benefiting from lifestyle changes or metformin, a study concluded.

To determine whether some patients were more or less likely to benefit from metformin or a structured lifestyle modification program, researchers conducted a post hoc analysis of data from the Diabetes Prevention Program, a randomized controlled trial among ambulatory care patients who had evidence of impaired glucose metabolism but who had not yet developed diabetes.

Criteria were designed to identify patients who were at high risk for developing diabetes. Researchers noted that they did not use the American Diabetes Association's diagnostic criteria for pre-diabetes but instead targeted patients with a body mass index of 24 kg/m² or higher (22 kg/m² or higher in Asians), a fasting plasma glucose concentration of 95 to 125 mg/dL (5.3 to 7 mmol/L), and a glucose concentration of 140 to 199 mg/dL (7.8 to 11 mmol/L) 2 hours after a 75-g oral glucose load.

Next, intervention groups received either metformin or a lifestyle modification program with the goals of weight loss and physical activity. Results appeared online Feb. 19 at The BMJ.

Of the 3,081 participants with impaired glucose metabolism at baseline, 655 (21%) developed diabetes over a median of 2.8 years. The lifestyle intervention provided a 6-fold greater absolute risk reduction in the highest risk quarter than in the lowest risk quarter, with patients in the lowest risk quarter seeing a 3-year absolute risk reduction of 4.9% (number needed to treat [NNT], 20.4) versus 28.3% (NNT, 3.5) in the highest risk quarter. Metformin's benefits were seen almost entirely in patients in the top quarter of risk of diabetes, and no benefit was seen in the lowest risk quarter. Participants in the highest risk quarter averaged a 21.4% 3-year absolute risk reduction (NNT, 4.6) from metformin.

The authors noted that average reported benefit for metformin was distributed very unevenly across the study population, with the quarter of patients at the highest risk for developing diabetes receiving a dramatic benefit but the remainder of the study population receiving modest or no benefit.

“Although patients at lower risk also received a much smaller absolute reduction from the lifestyle intervention than did higher risk patients, the relative effects of the lifestyle intervention were fairly constant across risk groups (hazard ratio=0.42),” the authors wrote. “These results could decrease drug overuse, help to prioritize lifestyle programs, and be a model for the secondary analysis of randomized trials.”