Saxagliptin

Additional information

For type 1 diabetes mellitus when diagnosed under the age of 15, the prevalence between boys and girls is similar. In adult populations of patients with both type 1 and 2 diabetes, the differences between the sexes in prevalence seem to vary depending on several factors such as incidence of disease, age groups and ethnicities studied.  Studies indicate that men in the early middle age display a higher prevalence of type 2 diabetes mellitus compared with women in the same age group [1]. In a nationwide population-based pharmaco-epidemiological study in Sweden, the total age-standardized prevalence of pharmacologically and non-pharmacologically treated diabetes (2012) was 56% for men and 39% for women [2].

Pharmacokinetics and dosing

In a review on the effect and safety of saxagliptin [1], data from a single-dose study on sex- differences of saxagliptin (10 mg) pharmacokinetics (PK) in healthy subjects were investigated [3]. There were no sex differences in saxagliptin PK parameters, although women had a slightly higher exposure (~25%) than men. The conclusion from Boulton et al.  [3] was that dose adjustment for patient’s sex was unnecessary [4].

In a study that evaluated the bioequivalence and safety of two fixed-combination drug products of dapagliflozin/saxagliptin/metformin extended release (XR FCDPs) to the individual components (ICs) in healthy subjects (55 men, 29 women), the Cmax and AUC of the study drugs were compared between women and men to assess sex differences in exposure. Both XR FCDPs were bioequivalent to their ICs. In both cohorts (XR FCDPs vs ICs), exposure was higher in women compared to men. The AUC of dapagliflozin, saxagliptin, 5-OH saxagliptin, and metformin was 8%-18%, 16%-18%, 25%-27%, and 3%-14% higher in women than men, respectively. According to the authors, this could potentially be due to the lower body weight in women [5].

Effects

According to the original manufacturer [6], reductions in HbA1c were seen across subgroups and regardless of a patient’s sex. Published controlled studies on differences between men and women regarding the efficacy of saxagliptin are lacking.

Adverse effects

In patients with type 2 diabetes from the SAVOR-TIMI 53 trial (11037 men, 5455 women), the incidence of fractures was calculated. The risk of fractures was higher in women than men (HR 1.84; 95%CI 1.53-2.21) [7].

In the SAVOR-TIMI 53 trial, the frequency of cancer events with saxagliptin treatment was investigated in patients with type 2 diabetes (11037 men, 5455 women). Male sex was found to be an independent predictor of cancer [8].

The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors was evaluated in an observational study from Taiwan. The subgroup analysis showed a lower risk of incident atrial fibrillation for SGLT2 inhibitors (9091 men, 6515 women) versus DPP-4 inhibitors (6911 men, 5472 women) in women compared to men with type 2 diabetes (HR men 0.51, HR women 0.70, p interaction =0.10) [9].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).