Detailed
Information
Hypoglycemia
in the AWARD Studies
Across
the AWARD studies, documented symptomatic hypoglycemia was defined as
a PG ≤70 mg/dL with or without signs or symptoms associated
with hypoglycemia while severe hypoglycemia was defined as a
hypoglycemic event that required the assistance of another person for
treatment. Hypoglycemic events that occurred between bedtime and
waking were designated as nocturnal.1-10
AWARD
Studies in Which Patients Received Dulaglutide Without Concomitant
Treatment With a Sulfonylurea or Insulin
In
the 5 AWARD studies in which dulaglutide was not used concomitantly
with a sulfonylurea or insulin, the duration of the studies ranged
from 24 to 104 weeks. The incidence and mean rate, defined as
episodes/patient/year, of documented symptomatic and severe
hypoglycemia were similar across treatment groups.1-5
Across
the 5 AWARD studies, the incidence of documented symptomatic
hypoglycemia ranged from
1.4%
to 10.9% in the dulaglutide 1.5 mg treatment groups, and
2.1%
to 6.3% in the dulaglutide 0.75 mg treatment groups.1-5,11
Of
the patients treated with dulaglutide, severe hypoglycemia was only
reported in 1 patient of whom received dulaglutide 0.75 mg.5
AWARD
Studies in Which Patients Received Dulaglutide and Concomitant
Treatment With a Sulfonylurea or Insulin
In
the 5 AWARD studies in which dulaglutide was used concomitantly with
a sulfonylurea or insulin, the duration of the studies ranged from 24
to 78 weeks.6-10
Overall, the incidence and mean rate of documented symptomatic,
nocturnal, and severe hypoglycemia were lower in patients treated
with dulaglutide 1.5 mg or dulaglutide 0.75 mg compared with those
treated with an active comparator along with a sulfonylurea or
insulin.7,9,10
Across
the 5 AWARD studies, the incidence of documented symptomatic
hypoglycemia ranged from
11.3%
to 80.8% in the dulaglutide 1.5 mg treatment groups, and
39%
to 85.6% in the dulaglutide 0.75 mg treatment groups.6-10
The
incidence of nocturnal hypoglycemia ranged from
6.7%
to 54.3% in the dulaglutide 1.5 mg treatment groups, and
23.2%
to 53.8% in the dulaglutide 0.75 mg treatment groups.6-10
The
incidence of severe hypoglycemia ranged from
0%
to 3.4% in the dulaglutide 1.5 mg treatment groups, and
0%
to 3% in the dulaglutide 0.75 mg treatment groups.6-10
AWARD
Studies With Insulin Glargine as Comparator
Overall,
the incidence and mean rate of documented symptomatic, nocturnal, and
severe hypoglycemia were lower in patients treated with dulaglutide
1.5 mg or dulaglutide 0.75 mg compared with those treated with the
active comparator insulin glargine.7,9,10
Use
of Dulaglutide With Medications Known to Cause Hypoglycemia
The
risk of hypoglycemia is increased when dulaglutide is used in
combination with insulin secretagogues, such as sulfonylureas, or
insulin. Patients may require a lower dose of the sulfonylurea or
insulin to reduce the risk of hypoglycemia in this setting.12
References
1.
Umpierrez G, Tofé Povedano S, Pérez Manghi F, et al.
Efficacy and safety of dulaglutide monotherapy versus metformin in
type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes
Care. 2014;37(8):2168-2176. https://doi.org/10.2337/dc13-2759
2.
Weinstock 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
3.
Dungan KM, Povedano ST, Forst T, et al. Once-weekly dulaglutide
versus once-daily liraglutide in metformin-treated patients with type
2 diabetes (AWARD-6): a randomised, open-label, phase 3,
non-inferiority trial. Lancet. 2014;384(9951):1349-1357.
https://doi.org/10.1016/S0140-6736(14)60976-4
4.
Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of
dulaglutide added onto pioglitazone and metformin versus exenatide in
type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes
Care. 2014;37(8):2159-2167. https://doi.org/10.2337/dc13-2760
5.
Ludvik B, Frías JP, Tinahones FJ, et al. Dulaglutide as
add-on therapy to SGLT2 inhibitors in patients with inadequately
controlled type 2 diabetes (AWARD-10): a 24-week, randomised,
double-blind, placebo-controlled trial. Lancet Diabetes
Endocrinol. 2018;6(5):370-381.
https://doi.org/10.1016/S2213-8587(18)30023-8
6.
Dungan KM, Weitgasser R, Perez Manghi F, et al. A 24-week study to
evaluate the efficacy and safety of once-weekly dulaglutide added on
to glimepiride in type 2 diabetes (AWARD-8). Diabetes Obes Metab.
2016;18(5):475-482. http://dx.doi.org/10.1111/dom.12634
7.
Giorgino F, Benroubi M, Sun JH, et al. Efficacy and safety of
once-weekly dulaglutide versus insulin glargine in patients with type
2 diabetes on metformin and glimepiride (AWARD-2). Diabetes Care.
2015;38(12):2241-2249. https://doi.org/10.2337/dc14-1625
8.
Pozzilli P, Norwood P, Jódar E, et al. Placebo-controlled,
randomized trial of the addition of once-weekly glucagon-like
peptide-1 receptor agonist dulaglutide to titrated daily insulin
glargine in patients with type 2 diabetes (AWARD-9). Diabetes Obes
Metab. 2017;19(7):1024-1031. http://dx.doi.org/10.1111/dom.12937
9.
Blonde L, Jendle J, Gross J, et al. Once-weekly dulaglutide versus
bedtime insulin glargine, both in combination with prandial insulin
lispro, in patients with type 2 diabetes (AWARD-4): a randomised,
open-label, phase 3, non-inferiority study. Lancet.
2015;385(9982):2057-2066.
https://doi.org/10.1016/S0140-6736(15)60936-9
10.
Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus
insulin glargine in patients with type 2 diabetes and
moderate-to-severe chronic kidney disease (AWARD-7): a multicentre,
open-label, randomised trial. Lancet Diabetes Endocrinol.
2018;6(8):605-617. https://doi.org/10.1016/S2213-8587(18)30104-9
11.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
12.
Trulicity [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
Glossary
AWARD
= Assessment of Weekly AdministRation of LY2189265 in Diabetes
PG =
plasma glucose