Trulicity® (dulaglutid): Hypoglykemi

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. http://dx.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