Treatment of genotyped diabetic patients with DPP-IV inhibitors such as linagliptin

#The invention describes DPP-4 inhibitors, pharmaceutical compositions or combinations comprising a DPP-4 inhibitor as defined herein and optionally one or more other active substances, for use in methods of treatment or prevention as described herein, such as e.g. of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance, impaired fasting blood glucose and hyperglycemia inter alia. In a particular embodiment, the therapeutic and/or preventive methods of this invention comprise the step of identifying a patient being susceptible to the treatment and/or prevention, said identifying comprising testing whether the patient has variation(s) in one or more genes associated with metabolic diseases (e.g. whether the patient is of a TCF7L2 risk genotype as described herein) or whether the patient is of respective wild-type genotype (e.g. whether the patient is of TCF7L2 wild genotype as described herein), and the further step of administering such DPP-4 inhibitor, pharmaceutical composition or combination to the patient determined as being susceptible.

#Type 2 diabetes is an increasingly prevalent disease that due to a high frequency of complications leads to a significant reduction of life expectancy. Because of diabetes-associated microvascular complications, type 2 diabetes is currently the most frequent cause of adult-onset loss of vision, renal failure, and amputations in the industrialized world. In addition, the presence of type 2 diabetes is associated with a two to five fold increase in cardiovascular disease risk.

#After long duration of disease, most patients with type 2 diabetes will eventually fail on oral therapy and become insulin dependent with the necessity for daily injections and multiple daily glucose measurements.

#FIG. 1 shows the baseline HbA1c values for the whole patient population of the studies (full analysis set, FAS), for the subpopulation for which genetic analyses are performed (full analysis set for pharmacogenetic analyses, FASG), as well as for the subgroups defined by SNP rs7903146 in TCF7L2 genotypes (CC, CT, TT) of this subpopulation.

#FIG. 2 shows the association of SNP rs7903146 in TCF7L2 with linagliptin response.

#The term “active ingredient” of a pharmaceutical composition or combination of the present invention means the DPP-4 inhibitor and/or, if present, the second antidiabetic agent and/or, if present, the third antidiabetic agent of the present invention.

#The term “body mass index” or “BMI” of a human patient is defined as the weight in kilograms divided by the square of the height in meters, such that BMI has units of kg/m2.

#The term “overweight” is defined as the condition wherein the individual has a BMI greater than or 25 kg/m2 and less than 30 kg/m2. The terms “overweight” and “pre-obese” are used interchangeably.