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Trulicity ® (dulaglutide)
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What is known about the long-term safety of Trulicity® (dulaglutide)?
In AWARD-5, over 104 weeks, more AEs were reported with each dulaglutide dose (0.75 and 1.5 mg) than with sitagliptin. In REWIND (median follow-up, 5.4 years), frequencies of AEs of special interest were similar between dulaglutide 1.5 mg and placebo.
Safety data on long-term treatment with dulaglutide
AWARD-5 Study
AWARD-5 was an adaptive, multicenter, randomized, 104-week, double-blind study that compared once-weekly dulaglutide 1.5 mg and dulaglutide 0.75 mg treatments with once-daily sitagliptin 100 mg and placebo in patients with type 2 diabetes inadequately controlled with metformin.1,2
Treatment with dulaglutide was associated with a significantly (p<.05) higher incidence of gastrointestinal (GI) treatment-emergent adverse events (TEAEs) than treatment with sitagliptin.1,2
Nausea, diarrhea, and vomiting were the most commonly reported adverse events (AEs) with the incidence highest after 2 weeks of treatment, with decreasing incidence at following visits.2
Both dulaglutide 1.5 mg and dulaglutide 0.75 mg treatment doses reported more AEs than the sitagliptin treatment group due to greater incidence of GI AEs ().2
A similar incidence of serious AEs was reported across treatment groups ().2
Variablea |
DULA 1.5 mg |
DULA 0.75 mg |
SITA 100 mg |
Treatment-emergent AEs ≥1 |
259 (85) |
255 (84) |
242 (77) |
Treatment-emergent GI AEs in ≥5% of participants |
|||
Nausea |
53 (17)b |
44 (15)b |
21 (7) |
Vomiting |
41 (14)b |
25 (8)b |
11 (4) |
Diarrhea |
49 (16)b |
36 (12)b |
18 (6) |
Abdominal pain |
21 (7) |
13 (4) |
11 (4) |
Abdominal distention |
13 (4) |
15 (5) |
3 (1) |
Dyspepsia |
18 (6) |
19 (6) |
14 (4) |
Pancreatic enzymes, median (Q1,Q3) [U/L] |
|||
Lipase |
6 (-1,14) |
6 (-1,18) |
3 (-2,9) |
Total amylase |
6 (-1,15) |
7 (-1,17) |
3 (-3,12) |
p-Amylase |
4 (0,9) |
4 (0,11) |
2 (-1,7) |
Pancreatitis |
0 (0) |
0 (0) |
2 (0.6) |
Serious AEs |
36 (12) |
23 (8) |
32 (10) |
Infections and infestations |
7 (2) |
3 (1) |
5 (2) |
Cardiac disorders |
6 (2) |
2 (1) |
4 (1) |
Neoplasms |
5 (2) |
3 (1) |
5 (2) |
GI AEs |
4 (1) |
2 (1) |
4 (1) |
Renal/urinary disorders |
5 (2) |
2 (1) |
0 (0) |
Death |
1 (<1) |
0 (0) |
2 (1) |
Injection site reactions |
4 (1.3) |
3 (1.0) |
3 (1.0) |
Hypoglycemiac, mean (SD) |
|||
Total |
0.0 (0.2) |
0.0 (0.5) |
0.0 (0.3) |
Documented symptomatic |
0.0 (0.1) |
0.0 (0.5) |
0.0 (0.3) |
Discontinuation resulting from AEs |
63 (21) |
64 (21) |
65 (21) |
Vital signs, LSM (SE) |
|||
Systolic blood pressure, mm Hg |
-0.1 (0.8) |
1.3 (0.8) |
<0.1 (0.8) |
Diastolic blood pressure, mm Hg |
0.4 (0.5) |
1.4 (0.5)b |
-0.4 (0.5) |
Pulse rate, beats/min |
2.3 (0.5)d |
2.8 (0.5)d |
-0.8 (0.5) |
Abbreviations: AE = adverse event; DULA = dulaglutide; GI = gastrointestinal; LSM = least squares mean; Q1 = first quartile; Q3 = third quartile; SITA = sitagliptin; U/L = units per liter.
aData presented as n (%) unless otherwise indicated.
bp<.05 vs SITA.
c<54 mg/dL cutoff, 1-year adjusted rate.
dp<.001 vs SITA.
REWIND Study
The REWIND study was an event-driven, randomized, double-blind, phase 3 cardiovascular (CV) outcomes study of dulaglutide.4
The study evaluated the effect on major adverse cardiovascular events (MACE-3, defined as the composite of CV death, nonfatal myocardial infarction, or nonfatal stroke) and other serious outcomes with once-weekly dulaglutide 1.5 mg treatment compared with placebo when added to standard of care in participants 50 years of age and older with type 2 diabetes
- with established CV disease, or
- without established CV disease with multiple CV risk factors.4
A total of 9901 patients were randomized to receive dulaglutide (n=4949) or placebo (n=4952) and followed up for a median of 5.4 years.4
During the follow-up, GI AEs were reported by 47·4% of participants who received dulaglutide compared to 34·1% of participants who received placebo (p<.001).3,4
TEAE, n (%) |
Dulaglutide (N=4949) |
Placebo (N=4952) |
Nausea |
737 (14.89)a |
271 (5.47) |
Diarrhea |
671 (13.56)a |
442 (8.93) |
Constipation |
364 (7.36)a |
213 (4.30) |
Vomiting |
330 (6.67)a |
159 (3.21) |
Dyspepsia |
292 (5.90)a |
148 (2.99) |
Abdominal pain |
213 (4.30) |
182 (3.68) |
Abbreviations: N = total number of randomized patients in each treatment group; n = number of patients with adverse event in each treatment group; TEAE = treatment-emergent adverse event.
ap<.001 vs placebo.
Dulaglutide did not differ significantly from placebo in frequencies of prespecified AEs of special interest including first study drug discontinuation, serious GI events, severe hypoglycemia, cancers, or pancreatitis ().4
Parametera |
Dulaglutide |
Placebo |
First study drug DC |
2092 (42.3) |
2171 (43.8) |
Acute pancreatitisb |
23 (0.5) |
13 (0.3) |
Any cancerc |
351 (7.1) |
348 (7.0) |
Medullary thyroid carcinoma or C-cell hyperplasiad |
1 (<0.1) |
0 |
Thyroid cancer |
7 (0.1) |
3 (0.1) |
Pancreatic cancer |
19 (0.4) |
12 (0.2) |
Serious GI event |
120 (2.4) |
117 (2.4) |
Serious hepatic event |
25 (0.5) |
40 (0.8) |
Serious renal or urinary evente |
84 (1.7) |
93 (1.9) |
Immune reactions |
8 (0.2) |
20 (0.4) |
Severe hypoglycemia |
64 (1.3) |
74 (1.5) |
Supraventricular tachycardia or CV conduction disorders |
216 (4.4) |
192 (3.9) |
Abbreviations: CV = cardiovascular; DC = discontinuation; GI = gastrointestinal; N = total number of randomized patients in each treatment group; n = number of patients with adverse event in each treatment group.
aData presented as n (%).
bBased on the first occurrence of acute pancreatitis, diagnosed on the basis of at least 2 of the 3 diagnostic criteria (symptoms, elevated pancreatic enzymes, or an abnormal pancreatic image).
cExcluding nonmelanoma skin cancers.
dThere were no cases of medullary thyroid carcinoma.
eBased on a search of the REWIND database for any reported adverse event linked to acute renal failure.
References
1Nauck M, Weinstock RS, Umpierrez GE, et al. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care. 2014;37(8):2149-2158. http://dx.doi.org/10.2337/dc13-2761
2Weinstock RS, Guerci B, Umpierrez G, et al. Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 2 years in metformin-treated patients with type 2 diabetes (AWARD-5): a randomized, phase III study. Diabetes Obes Metab. 2015;17(9):849-858. http://dx.doi.org/10.1111/dom.12479
3Data on file, Eli Lilly and Company and/or one of its subsidiaries.
4Gerstein HC, Colhoun HM, Dagenais GR, et al; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121-130. https://doi.org/10.1016/S0140-6736(19)31149-3
Date of Last Review: 25 October 2023