Trulicity Switching Protocols: Moving To and From Dulaglutide Safely

Does the label describe how to switch?

No. The dosage section covers the starting dose, escalation, the missed-dose rule and how to change the weekly injection day [1]. It does not describe moving from semaglutide, tirzepatide, liraglutide or exenatide onto dulaglutide, or the reverse. The label says the weekly injection day can be changed if the last dose was given 3 or more days before the new day [1].

What the label does specify

The label gives a 0.75 mg once-weekly starting dose for Trulicity. It does not explain how to select a starting dose when changing from another GLP-1 receptor agonist [1]. The label says the dose may be increased to 1.5 mg after 4 weeks, then in 1.5 mg steps after at least 4 weeks on the current dose, to a maximum of 4.5 mg weekly in adults. For pediatric patients 10 years and older, the label gives a maximum of 1.5 mg weekly [1].

When Trulicity is initiated, the label says to consider reducing the dose of a sulfonylurea or insulin to reduce hypoglycemia risk [1]. With insulin glargine, glucose below 54 mg/dL occurred in 14.7% of patients on dulaglutide 1.5 mg versus 9.3% on placebo; with glimepiride, 3.3% versus 0% [1].

How dulaglutide compares in trials

These trials assigned patients to a drug at the start rather than studying a switch from one product to another.

SUSTAIN 7, open-label, 1,201 patients on metformin: HbA1c fell 1.8 points with semaglutide 1 mg versus 1.4 with dulaglutide 1.5 mg at 40 weeks [2].

SURPASS-CVOT randomized 13,299 patients with type 2 diabetes and atherosclerotic cardiovascular disease. After 134 exclusions, 13,165 patients were included in the modified intention-to-treat analysis; cardiovascular death, myocardial infarction or stroke occurred in 12.2% on tirzepatide and 13.1% on dulaglutide, meeting noninferiority but not superiority [3].

Kidney function, cardiovascular history and tolerability

Dulaglutide is presumed to be degraded into amino acids by general protein catabolism. Age, sex, race, body weight, and renal or hepatic impairment had no clinically relevant effect on its pharmacokinetics [1].

The cardiovascular indication covers adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors [1]. REWIND randomized 9,901 adults aged 50 or older, 31.5% with established cardiovascular disease, to dulaglutide 1.5 mg weekly or placebo. The composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death occurred in 12.0% versus 13.4% (hazard ratio 0.88, 95% CI 0.79 to 0.99) [5].

Gastrointestinal adverse reactions were reported in 21% of placebo recipients, 32% of patients receiving 0.75 mg, and 41% receiving 1.5 mg in the adult placebo-controlled pool; treatment was stopped for GI reasons by 0.2%, 1.3%, and 3.5%, respectively [1].