Glucose-dependent insulinotropic polypeptide (GIP) beyond its insulinotropic effects may regulate post-prandial lipid metabolism. While the insulinotropic action of GIP is known to be impaired in type 2 diabetes mellitus (T2DM), its adipogenic effect is unknown. We hypothesised GIP is anabolic in human subcutaneous adipose tissue (SAT) promoting triacylglycerol (TAG) deposition through re-esterification of non-esterified fatty acids (NEFA) and this effect may differ according to obesity status or glucose tolerance. Methods: 23 subjects, categorised in four groups: normoglycaemic lean (n=6), normoglycaemic obese, (n=6), obese with impaired glucose regulation (IGR) (n=6) and obese, T2DM (n=5) participated in a double-blind, randomised, crossover study involving a hyperglycaemic clamp with a 240 minute GIP infusion (2pmol kg^-1min^-1) or normal saline. Insulin, NEFA, SAT-TAG content and gene expression of key lipogenic enzymes were determined before and immediately after GIP/saline infusions. Results: GIP lowered NEFA concentrations in obese T2DM group despite diminished insulinotropic activity (mean NEFA AUC_0-4hr ± SEM, 41992 ±9843 µmol/L/min vs 71468 ±13605 with placebo, p=0.039; 95% CI 0.31 to 0.95). Additionally, GIP increased SAT-TAG in obese T2DM (1.78 ±0.4 vs 0.86 ±0.1 fold with placebo, p=0.043; 95% CI: 0.1 to 1.8). Such effect with GIP was not observed in other three groups despite greater insulinotropic activity. Reduction in NEFA concentration with GIP correlated with adipose tissue insulin resistance for all subjects (Pearson r=0.56, p=0.005). There were no significant gene expression changes in key SAT lipid metabolism enzymes. Conclusion: GIP appears to promote fat accretion and thus may exacerbate obesity and insulin resistance in T2DM.