January 18, 2019
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Combining metformin, intensive lifestyle marginally improves glycemic control, body mass

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Metformin therapy has a small effect on glycemic control and changes in body mass when combined with intensive lifestyle interventions in adults with type 2 diabetes and overweight or obesity, according to findings published in Metabolism.

“The established independent, antihyperglycemic effects of pharmacotherapies and lifestyle intervention have led to their simultaneous prescriptions to manage or treat type 2 diabetes,” Normand G. Boulé, PhD, a professor and associate dean in the faculty of kinesiology, sport and recreation at the University of Alberta in Edmonton, Canada, and colleagues wrote. “Given the frequency in which metformin and lifestyle intervention are concurrently prescribed as a first-line treatment for type 2 diabetes, surprisingly few studies have examined their interplay.”

Data from the Look AHEAD trial were used by the researchers for analysis. A total of 1,982 adults with type 2 diabetes who had a BMI greater than 25 kg/m2 (mean age, 57.4 years; 58.2% women; mean HbA1c, 7.4%) were recruited between August 2001 and April 2004 for the study.

Participants took part in intensive lifestyle intervention or diabetes education programs. Intensive lifestyle interventions included meetings with exercise specialists, dietitians and behavioral psychologists, with a goal to maintain weight loss of at least 7% per month via 175 minutes per week of moderately intensive physical activity and a lower calorie diet. Diabetes education programs included three group sessions in a year about healthy eating and physical activity. In addition, participants in each group were divided into two groups based on whether they received metformin therapy.

The researchers measured HbA1c, fasting plasma glucose, body mass and cardiorespiratory fitness for all participants after 1 year.

An interaction effect observed between metformin therapy and intensive lifestyle interaction (P = .031) was not seen after sensitivity analysis, which excluded participants who changed antihyperglycemic medications. The combination of metformin and intervention led to an average reduction of 0.72% in HbA1c compared with a reduction of 0.75% in participants with intervention and no metformin after sensitivity analysis. However, metformin combined with diabetes education programs led to a greater reduction in HbA1c (–0.18%) compared with no metformin and diabetes education (–0.16%).

When considered in the context of FPG, the interaction effect between metformin therapy and lifestyle intervention was significant both before (P = .043) and after (P = .04) sensitivity analysis. FPG levels decreased by an average of 21.5 mg/dL for participants who underwent intervention with metformin therapy, which compared with an average decrease of 24.2 mg/dL in intervention with no metformin participants. FPG levels declined by a greater margin in participants who combined metformin with diabetes education (–11 mg/dL) compared with participants with no metformin and diabetes education (–3.4 mg/dL).

Sensitivity analysis revealed an interaction effect of metformin with intervention on body mass (P = .005), which was not present before the adjustment. However, participants who underwent intervention with metformin lost less body mass (–7.2 kg) compared with participants with intervention and no metformin (–9.1 kg). Metformin with diabetes education led to an average loss of body mass of 0.9 kg compared with an average loss of 1 kg in participants with no metformin and diabetes education.

“With established independent effects of pharmacotherapies and lifestyle intervention, combined therapies have widely been recommended with an expectation of further benefit,” the researchers wrote. “While the small magnitude of the observed interaction should not discourage the concomitant use of these therapies, the interaction between metformin therapy and lifestyle intervention on glycemia highlights the complicated nature of combining therapies.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.