Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes Prevention Program.

Objective: We tested genetic associations with weight loss and weight regain in the Diabetes Prevention Program, a randomized controlled trial of weight loss-inducing interventions (lifestyle and metformin) versus placebo.

Research Design And Methods: Sixteen obesity-predisposing single nucleotide polymorphisms (SNPs) were tested for association with short-term (baseline to 6 months) and long-term (baseline to 2 years) weight loss and weight regain (6 months to study end).

Results: Irrespective of treatment, the Ala12 allele at PPARG associated with short- and long-term weight loss (-0.63 and -0.93 kg/allele, P ≤ 0.005, respectively). Gene-treatment interactions were observed for short-term (LYPLAL1 rs2605100, P(lifestyle*SNP) = 0.032; GNPDA2 rs10938397, P(lifestyle*SNP) = 0.016; MTCH2 rs10838738, P(lifestyle*SNP) = 0.022) and long-term (NEGR1 rs2815752, P(metformin*SNP) = 0.028; FTO rs9939609, P(lifestyle*SNP) = 0.044) weight loss. Three of 16 SNPs were associated with weight regain (NEGR1 rs2815752, BDNF rs6265, PPARG rs1801282), irrespective of treatment. TMEM18 rs6548238 and KTCD15 rs29941 showed treatment-specific effects (P(lifestyle*SNP) < 0.05).

Conclusions: Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention.