Trulicity® (dulaglutid): Användning med DPP-4-hämmare

Detailed Information

The use of DPP-4 inhibitors, such as sitagliptin, in combination with dulagutide, was not evaluated in the clinical studies assessing dulaglutide.

Coadministration of Dulaglutide With Sitagliptin

An open-label, 2-period, crossover, clinical pharmacology study was done in 29 patients with T2DM that evaluated the mutual effects on the PK of both dulaglutide 1.5 mg and sitagliptin 100 mg.¹

Potential for Dulaglutide to Influence the Pharmacokinetics of Sitagliptin

Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products.²

Sitagliptin exposure was unaffected when coadministered with a single dose of dulaglutide. Following coadministration with 2 consecutive doses of dulaglutide, resulted in a decrease of the sitagliptin

• AUC_(0-τ) and by approximately 7.4 %

• C_max by approximately 23.1 %,.

Sitagliptin t_max increased approximately 0.5 hours following coadministration with dulaglutide compared to sitagliptin alone.²

Based on the analysis, no clinically significant effect on the PK of sitagliptin was seen and no dose adjustment was recommended for sitagliptin when coadministered with dulaglutide (Figure 1).¹

Figure 1. Impact of Dulaglutide on the Pharmacokinetics of Coadministered Dipeptidyl Peptidase-4 Inhibitor, Sitagliptin¹

Abbreviations: AUC = area under the time-concentration curve; Cmax = maximum concentration; PK = pharmacokinetic.
Note: Reference group is coadministered medication given alone.

Potential for Coadministered Sitagliptin to Influence the Pharmacokinetics of Dulaglutide

Sitagliptin can produce up to 80 % inhibition of DPP‑4 over a 24‑hour period.²

Compared to dulaglutide being taken alone, the coadministration of a single dose of dulaglutide 1.5 mg with steady-state sitagliptin 100 mg resulted in dulaglutide's increase in 

• the area under the AUC by approximately 38%

• Cmax by approximately 27%, and

• Tmax concentration of approximately 24 hours.^1,2 

Therefore, dulaglutide does have a high degree of protection against DPP‑4 inactivation. The increased exposure may enhance the effects of dulaglutide on blood glucose levels.²

References

1. Geiser J, de la Peña A, Cui X, et al. No dose adjustment is needed when coadministering dulaglutide with once-daily sitagliptin. Poster presented at: American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting: March 15-18, 2017; Washington, D.C.

2. Trulicity [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

Glossary

AUC = area under the curve

C_max = maximum plasma concentration

DPP-4 = dipeptidyl peptidase-4

GLP-1 RA = glucagon-like peptide-1 receptor agonist

PK = pharmacokinetic

T2DM = type 2 diabetes mellitus

T_max = time to maximum concentration