The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial.
BACKGROUND
The metabolic syndrome is a high-risk state for diabetes and cardiovascular disease. Little is known about its prevalence and prevention in those with impaired glucose tolerance.


OBJECTIVE
To determine the prevalence of the metabolic syndrome at baseline in the Diabetes Prevention Program and the effect of intensive lifestyle intervention and metformin therapy on the syndrome's incidence and resolution.


METHODS
Randomized, controlled clinical trial.


METHODS
Research and community-based centers.


METHODS
Participants had impaired glucose tolerance (World Health Organization criteria plus fasting plasma glucose level >or=5.3 mmol/L [>or=95 mg/dL]) and were followed for a mean of 3.2 years after random assignment to intensive lifestyle intervention, metformin therapy, or placebo.


METHODS
Metformin, 850 mg twice daily, or intensive lifestyle intervention designed to achieve and maintain a 7% weight loss and 150 minutes of exercise per week.


METHODS
The metabolic syndrome was defined as having 3 or more characteristics (waist circumference; blood pressure; and levels of high-density lipoprotein cholesterol, triglycerides, and fasting plasma glucose) that met criteria from the National Cholesterol Education Program Adult Treatment Panel III.


RESULTS
Fifty-three percent of participants (n = 1711) had the metabolic syndrome at baseline; incidence did not vary substantially by age. However, low levels of high-density lipoprotein cholesterol predominated in younger participants (age 25 to 44 years), and high blood pressure predominated in older participants (age 60 to 82 years). In life-table analyses (log-rank test), incidence of the metabolic syndrome was reduced by 41% in the lifestyle group (P < 0.001) and by 17% in the metformin group (P = 0.03) compared with placebo. Three-year cumulative incidences were 51%, 45%, and 34% in the placebo, metformin, and lifestyle groups, respectively. There was no significant heterogeneity by ethnic group.


CONCLUSIONS
The study involved a volunteer group with impaired glucose tolerance, which limits generalizability.


CONCLUSIONS
The metabolic syndrome affected approximately half of the participants in the Diabetes Prevention Program at baseline. Both lifestyle intervention and metformin therapy reduced the development of the syndrome in the remaining participants.
Orchard
Trevor J
TJ
Diabetes Prevention Program Coordinating Center, The Biostatistics Center, George Washington University, Rockville, Maryland 20852, USA.
Temprosa
Marinella
M
Goldberg
Ronald
R
Haffner
Steven
S
Ratner
Robert
R
Marcovina
Santica
S
Fowler
Sarah
S
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004038:Diet, Reducing; D005081:Exercise Therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008019:Life Style; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000517:prevention & control*; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
D007004:Hypoglycemic Agents; D008687:Metformin