10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study.
BACKGROUND
In the 2.8 years of the Diabetes Prevention Program (DPP) randomised clinical trial, diabetes incidence in high-risk adults was reduced by 58% with intensive lifestyle intervention and by 31% with metformin, compared with placebo. We investigated the persistence of these effects in the long term.


METHODS
All active DPP participants were eligible for continued follow-up. 2766 of 3150 (88%) enrolled for a median additional follow-up of 5.7 years (IQR 5.5-5.8). 910 participants were from the lifestyle, 924 from the metformin, and 932 were from the original placebo groups. On the basis of the benefits from the intensive lifestyle intervention in the DPP, all three groups were offered group-implemented lifestyle intervention. Metformin treatment was continued in the original metformin group (850 mg twice daily as tolerated), with participants unmasked to assignment, and the original lifestyle intervention group was offered additional lifestyle support. The primary outcome was development of diabetes according to American Diabetes Association criteria. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00038727.


RESULTS
During the 10.0-year (IQR 9.0-10.5) follow-up since randomisation to DPP, the original lifestyle group lost, then partly regained weight. The modest weight loss with metformin was maintained. Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years (95% CI 4.1-5.7) in the intensive lifestyle intervention group, 7.8 (6.8-8.8) in the metformin group, and 11.0 (9.8-12.3) in the placebo group. Diabetes incidence rates in this follow-up study were similar between treatment groups: 5.9 per 100 person-years (5.1-6.8) for lifestyle, 4.9 (4.2-5.7) for metformin, and 5.6 (4.8-6.5) for placebo. Diabetes incidence in the 10 years since DPP randomisation was reduced by 34% (24-42) in the lifestyle group and 18% (7-28) in the metformin group compared with placebo.


CONCLUSIONS
During follow-up after DPP, incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group, but the cumulative incidence of diabetes remained lowest in the lifestyle group. Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years.


BACKGROUND
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Knowler
William C
WC
Fowler
Sarah E
SE
Hamman
Richard F
RF
Christophi
Costas A
CA
Hoffman
Heather J
HJ
Brenneman
Anne T
AT
Brown-Friday
Janet O
JO
Goldberg
Ronald
R
Venditti
Elizabeth
E
Nathan
David M
DM
D000368:Aged; D000704:Analysis of Variance; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D016640:Diabetes, Gestational / Q000209:etiology; D004311:Double-Blind Method; D005081:Exercise Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008019:Life Style; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D050177:Overweight / Q000150:complications / Q000517:prevention & control; D010353:Patient Education as Topic; D011247:Pregnancy; D012044:Regression Analysis; D040242:Risk Reduction Behavior; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D015431:Weight Loss / Q000187:drug effects
D007004:Hypoglycemic Agents; D008687:Metformin