Dulaglutide

Additional information

Studies indicate that men in the early middle age have a higher prevalence of type 2 diabetes mellitus compared with women in the same age group [1]. In Sweden, the age-standardized prevalence of pharmacologically and non-pharmacologically treated diabetes was 56% for men and 39% for women in 2012 [2].

Pharmacokinetics and dosing

According to the product information, patient’s sex had no clinically meaningful effect on the pharmacokinetics of dulaglutide [3]. Analysis of pharmacokinetic data from phase 2 and phase 3 clinical studies suggest that no dose adjustment of dulaglutide is necessary based on patient’s sex [4].

Effects

Patient’s sex had no significant effect on any clinical or laboratory outcome when the efficacy, safety, and the factors predicting the response of dulaglutide were evaluated in a retrospective study (472 men, 310 women) [5].

Pooled analysis from clinical trials of patients treated with dulaglutide 1.5 mg (969 men, 989 women) showed similar reduction in HbA1c at 6 months compared with baseline, in men and women [6]. In a retrospective study of GLP-1-RA agonist naïve patients treated with dulaglutide in a clinical setting, changes in HbA1c and body weight (≤30 months after baseline) were similar in men and women (687 men, 387 women) [7]. Data from six phase 3 clinical trials (5171 patients, 42-56% women) showed no consistent correlation between changes in weight and HbA1c, and patient’s sex was not related to different combinations of outcome responses [8].

A subgroup analysis of three phase 3 trials (648 men, 204 women) of once weekly dulaglutide 0.75 mg for 26 weeks in Japanese patients found that the change in HbA1c from baseline was similar for both men and women. Women had significantly greater weight loss compared to men (-0.05 kg vs -0.59 kg) [9].

Similar reductions in HbA1c were observed for men and women, both when dulaglutide was compared to liraglutide (341 men, 76 women) and insulin glargine (258 men, 103 women). Dulaglutide-treated women had the greatest mean weight loss across the treatments and sexes [10].

Adverse effects

Women had a higher incidence of nausea (percentage of patients experiencing nausea) compared to men (6.0% vs 10.7%) when treated with once weekly dulaglutide 0.75 mg for 26 weeks (649 men, 206 women) [9].

Greater proportions of women compared to men in the dulaglutide, liraglutide, and insulin glargine treatment groups experienced adverse events (range 72-87% women vs 58-73% men). Nausea, constipation, and diarrhea also generally occurred more frequently among women compared to men in all treatment groups. Incidence of early discontinuation of study drug due to adverse events was low (<10%) regardless of patient’s sex and treatment. The incidences of total or nocturnal hypoglycemia were similar between men and women in any treatment group [10].

A cohort study with register data from Sweden, Denmark, and Norway, comparing new-users of GLP-1-RAs and dipeptidyl peptidase 4 (DPP-4) inhibitors, assessed the risk of serious renal events in routine care. The use of GLP-1-RAs was associated with a significantly lower risk of renal replacement therapy and hospitalization for renal events, compared with DPP-4 inhibitor. The subgroup analysis (22 043 men, 16 688 women treated with GLP-1-RAs) showed no interaction between treatment status and patient’s sex [11].

Reproductive health issues

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