Trulicity ® (dulaglutid) injektion

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Trulicity® (dulaglutid): Mag-tarmbiverkningar i AWARD-11

En fas 3-studie visade signifikanta minskningar av HbA1c med dulaglutid 3 mg och/eller 4,5 mg med biverkningar som huvudsakligen var av mag-tarm karaktär.

Label information

Dulaglutide is indicated for the treatment of adults with insufficiently controlled T2DM as an adjunct to diet and exercise

  • as monotherapy when metformin is considered inappropriate due to intolerance or contraindications, and

  • in addition to other medicinal products for the treatment of diabetes.1

The recommended dose of dulaglutide is 0.75 mg once weekly as monotherapy.1

The recommended dose of dulaglutide is 1.5 mg once weekly as add-on therapy.1

For potentially vulnerable populations 0.75 mg once weekly can be considered as a starting dose.1

For additional glycaemic control,

  • the 1.5 mg dose may be increased after at least 4 weeks to 3 mg once weekly

  • the 3 mg dose may be increased after at least 4 weeks to 4.5 mg once weekly.

The maximum dose is 4.5 mg once weekly1

Detailed Information

The AWARD-11 trial was a phase 3, randomized, double-blind, active controlled, parallel-arm study that assessed the efficacy and safety of dulaglutide 3.0 mg and dulaglutide 4.5 mg compared to dulaglutide 1.5  mg in in patients with inadequately controlled T2DM on concomitant metformin therapy.2

The primary endpoint of the AWARD-11 trial was the change from baseline in HbA1c at 36 weeks in patients with inadequately controlled T2DM who were also receiving concomitant metformin therapy.2-4

Data from the AWARD-11 trial suggests that escalation from dulaglutide 1.5 mg to dulaglutide 3 mg or dulaglutide 4.5 mg once-weekly provided clinically relevant, dose-related improvements in glycemic control and BW with an acceptable safety profile.2

Gastrointestinal Adverse Events in Patients Taking Dulaglutide

Treatment with dulaglutide 4.5 mg resulted in significantly greater reductions in HbA1c, weight, FSG, and proportion achieving HbA1c <7.0% compared to dulaglutide 1.5 mg.2

The most frequently reported TEAEs in AWARD-11 were GI in nature (Table 1).2-4

Table 1. Most Frequently Reported GI TEAEs Reported in AWARD-112-4

Parameter

DULA 3.0 mg
(n=616)

DULA 4.5 mg
(n=614)

DULA 1.5 mg
(n=612)

Total
(n=1842)

P Valuea

36 weeks

Patients ≥1 TEAE, n (%)

351 (57.0)

378 (61.6)

346 (56.5)

1075 (58.4)

.140

Nausea

96 (15.6)

101 (16.4)

82 (13.4)

279 (15.1)

.305

Diarrhea

70 (11.4)

66 (10.7)

43 (7.0)

179 (9.7)

.018

Vomiting 

51 (8.3)

57 (9.3)

34 (5.6)

142 (7.7)

.036

Dyspepsia

31 (5.0)

16 (2.6)

17 (2.8)

64 (3.5)

.044

52 weeks

Patients ≥1 TEAE, n (%)

384 (62.3)

408 (66.4)

380 (62.1)

1172 (63.6)

.204

Nausea

99 (16.1)

106 (17.3)

87 (14.2)

292 (15.9)

.336

Diarrhea

74 (12.0)

71 (11.6)

47 (7.7)

192 (10.4)

.021

Vomitting

56 (9.1)

62 (10.1)

39 (6.4)

157 (8.5)

.048

Dyspepsia

31 (5.0)

17 (2.8)

17 (2.8)

65 (3.5)

.060

Abbreviations: AWARD = Assessment of Weekly AdministRation of LY2189265 in Diabetes; DULA = dulaglutide; GI = gastrointestinal; TEAE = treatment emergent adverse event.

a P values for overall treatment effect were computed using Fisher’s Exact test.

Consistent with the known safety profile of dulaglutide, the most common AEs were related to GI symptoms. The incidence was highest early after dulaglutide initiation and tended to wane over time.2,4

Nearly all cases of nausea, vomiting, and diarrhea reported by patients, >95% for each, were mild to moderate in severity.4

All safety findings for the AWARD-11 trial were similar across the elderly patient population, ≥ 65 years old, when compared to the general patient population.4

Gastrointestinal events are the most common TEAEs associated with the use of GLP-1 RAs. These events typically have an early onset, are mild or moderate in severity, and decrease in frequency with continued treatment.5,6

In single-dose studies, most GI AEs were reported during the first 2 to 3 days after dosing and usually diminished by 7 days of dosing with dulaglutide.4

In multiple-dose studies, these AEs were evaluated in daily and weekly intervals. Most of these AEs were reported during the first 2 to 3 days after the initial dose of dulaglutide and declined over the first week of dosing and after each subsequent dose.4

References

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

2. Frias JP, Nevárez Ruiz L, Li YG, et al. Efficacy and safety of higher dulaglutide doses (3.0 mg and 4.5 mg) when added to metformin in patients with type 2 diabetes: a phase 3, randomized, double-blind, parallel arm study (AWARD-11). J Endocr Soc. 2020;4(suppl 1):A1036. Endocrine Society abstract OR26-08. https://doi.org/10.1210/jendso/bvaa046.2057

3. Frias JP, Bonora E, Nevarez Ruiz LA, et al. Efficacy and safety of dulaglutide 3mg and 4.5mg vs. dulaglutide 1.5mg: 52-week results from AWARD-11. Diabetes. 2020;69(suppl 1). American Diabetes Association abstract 357-OR. https://doi.org/10.2337/db20-357-OR

4. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

5. Aroda VR, Ratner R. The safety and tolerability of GLP-1 receptor agonists in the treatment of type 2 diabetes: a review. Diabetes Metab Res Rev. 2011;27(6):528-542. https://doi.org/10.1002/dmrr.1202

6. Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond. Drugs Context. 2015;4:212283. https://doi.org/10.7573/dic.212283

Glossary

AE = adverse event

AWARD = Assessment of Weekly AdministRation of LY2189265 in Diabetes

BW = body weight

FSG = fasting serum glucose

GI = gastrointestinal

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

HbA1c = glycated hemoglobin

TEAE = treatment-emergent adverse event

T2DM = type 2 diabetes mellitus

Datum fӧr senaste ӧversyn 2020 M06 16


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