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Saxagliptin

Classification: C

Drug products: Komboglyze, Onglyza, Qtern

ATC code: A10BD10, A10BD21, A10BH03

Substances: saxagliptin, saxagliptin hydrate, saxagliptin hydrochloride

Summary

Published controlled studies on differences in efficacy of saxagliptin between men and women are lacking. Observational studies have found a higher risk of fractures in women, and an independent predictor of cancer in male patients with diabetes mellitus treated with 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).

Updated: 2021-05-12

Date of litterature search: 2021-03-10

References

  1. Gale EA, Gillespie KM. Diabetes and gender. Diabetologia. 2001;44(1):3-15. PubMed
  2. Jansson SP, Fall K, Brus O, Magnuson A, Wändell P, Östgren CJ et al. Prevalence and incidence of diabetes mellitus: a nationwide population-based pharmaco-epidemiological study in Sweden. Diabet Med. 2015;32(10):1319-28. PubMed
  3. Boulton DW, Goyal A, Li L, Kornhauser DM, Frevert U. The effects of age and gender on the singledose pharmacokinetics and safety of saxagliptin in healthy subjects [abstract]. Diabetes. 2008;57(suppl 1):A164.
  4. Deacon CF, Holst JJ. Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. Adv Ther. 2009;26(5):488-99. PubMed
  5. Tang W, Engman H, Zhu Y, Dayton B, Boulton DW. Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects. Clin Ther. 2019;41(8):1545-1563. PubMed
  6. Onglyza (saxagliptin). EPAR - Product information. European Medicines Agency (EMA) [updated 2021-03-03, cited 2021-03-22]
  7. Mosenzon O, Wei C, Davidson J, Scirica BM, Yanuv I, Rozenberg A, Hirshberg B, Cahn A, Stahre C, Strojek K, Bhatt DL, Raz I. Incidence of Fractures in Patients With Type 2 Diabetes in the SAVOR-TIMI 53 Trial. Diabetes Care. 2015;38(11):2142-50. länk
  8. Leiter LA, Teoh H, Mosenzon O, Cahn A, Hirshberg B, Stahre CA et al. Frequency of cancer events with saxagliptin in the SAVOR-TIMI 53 trial. Diabetes Obes Metab. 2016;18(2):186-90. PubMed
  9. Ling AW, Chan CC, Chen SW, Kao YW, Huang CY, Chan YH, Chu PH. The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors. Cardiovasc Diabetol. 2020;19(1):188. länk
  10. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2020 [cited 2021-03-10.] länk

Authors: Diana Rydberg, Linnéa Karlsson Lind

Reviewed by: Carl-Olav Stiller

Approved by: Karin Schenck-Gustafsson