Trulicity Side Effects Severity Distribution by Patient Phenotype

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What the label measures

The adult placebo-controlled pool covers 1,670 treated patients with a mean exposure of 23.8 weeks [1]. Investigators graded GI reactions as mild in 58% of cases on 0.75 mg and 48% on 1.5 mg, moderate in 35% and 42%, and severe in 7% and 11%; severe gastrointestinal adverse reactions were reported in 2.2% on 0.75 mg, 4.3% on 1.5 mg and 1.4% on placebo [1]. Any GI reaction was reported by 21% / 32% / 41% (placebo / 0.75 mg / 1.5 mg), and treatment was stopped for a GI reaction in 0.2% / 1.3% / 3.5% [1].

Dose is the modifier with numbers behind it

AWARD-11, a trial of 1,842 adults on metformin with adverse reactions reported through 36 weeks, compared 1.5 mg, 3 mg and 4.5 mg weekly: nausea 13.4%, 15.6% and 16.4%, vomiting 5.6%, 8.3% and 9.3% [1][2]. In AWARD-11, nausea and vomiting were reported more often at 4.5 mg than at 1.5 mg; the separate placebo-controlled pool also reported higher rates at 1.5 mg than at 0.75 mg [1].

Adults start at 0.75 mg weekly, may move to 1.5 mg after 4 weeks, then step up in 1.5 mg increments after at least 4 weeks on the current dose, to a maximum of 4.5 mg; the label says to follow this escalation to reduce the risk of gastrointestinal adverse reactions [1]. Trulicity is not recommended in patients with severe gastroparesis [1].

Insulin and sulfonylureas raise hypoglycemia rates

The label's concomitant-medication data concern hypoglycemia. With insulin glargine, glucose below 54 mg/dL occurred in 14.7% on 1.5 mg versus 9.3% on placebo, with severe hypoglycemia in 0.7% versus 0% [1]. Added to glimepiride, 3.3% on 1.5 mg versus 0% on placebo reached that threshold [1]. Over 78 weeks with a background sulfonylurea, glucose below 54 mg/dL occurred in 20% on 0.75 mg and 21% on 1.5 mg, with severe hypoglycemia in 0% and 0.7% [1]. The label says to consider reducing the insulin secretagogue or insulin dose when Trulicity is started [1].

Kidney function

Dulaglutide pharmacokinetics show no clinically relevant effect of renal or hepatic impairment, age, sex, race or body weight [1]. The label's renal warning is indirect: acute kidney injury has been reported, mostly in patients whose GI reactions caused dehydration, and the label says to monitor renal function in patients reporting reactions that could lead to volume depletion, especially during initiation and escalation [1]. The label gives no GI severity comparison by kidney function.

Children 10 and older

The pediatric trial randomised 154 patients aged 10 to under 18, and 150 were treated over a mean of 41.3 weeks [1]. The label describes the pediatric safety profile as consistent with adults except for injection-site reactions: 3.9% on 0.75 mg and 3.8% on 1.5 mg versus 2.0% on placebo [1]. The pediatric maximum is 1.5 mg weekly [1].