Trulicity (Dulaglutide) in Patients 65 and Older: Transitioning to Adult Care

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Does dulaglutide need a different dose after 65?

No. The label's pharmacokinetic summary states that age, sex, race, body weight and renal or hepatic impairment have no clinically relevant effect on dulaglutide exposure [1]. The dosing section gives one adult schedule with no older-adult variant: 0.75 mg subcutaneously once weekly, 1.5 mg after at least 4 weeks if additional glycemic control is needed, then increases in 1.5 mg steps at intervals of at least 4 weeks, up to 4.5 mg once weekly [1]. The half-life is about 5 days [1].

The label's only dose limit tied to age applies to younger patients: those 10 years and older follow the same 0.75 mg start but stop at 1.5 mg weekly, while the adult maximum is 4.5 mg [1].

On missed doses, the label says to give the missed dose if at least 3 days (72 hours) remain before the next scheduled dose, and otherwise skip it; the weekly day can be moved if the last dose was 3 or more days earlier [1]. Injections go into the abdomen, thigh or upper arm at any time of day, with or without food, rotating sites [1].

How much of the safety data comes from patients over 65?

Limited. The placebo-controlled pool behind the common adverse reaction table included 568 patients on placebo, 836 on 0.75 mg and 834 on 1.5 mg, with mean exposure of 23.8 weeks; the mean age was 56 years, 1% were 75 or older, and 96% had a baseline eGFR of 60 or above [1]. The 3 mg and 4.5 mg dose-ranging trial enrolled 1,842 adults on metformin [3].

A qualitative review of completed Phase 4 ClinicalTrials.gov studies in adults 65 and older identified 37 trials of GLP-1 receptor agonists with posted results, 7 of them involving dulaglutide. Across all 37 trials (not dulaglutide alone), gastrointestinal intolerance was reported at 15% to 30%, injection-site reactions at 5% or less, and hypoglycemia at under 5% [4].

Nausea, vomiting and volume depletion

In the adult placebo-controlled pool [1]:

• Nausea: 12.4% at 0.75 mg and 21.1% at 1.5 mg, versus 5.3% on placebo
• Diarrhea: 8.9% and 12.6%, versus 6.7%
• Vomiting: 6.0% and 12.7%, versus 2.3%
• Decreased appetite: 4.9% and 8.6%, versus 1.6%
• Any GI reaction: 32% and 41%, versus 21%
• Stopped treatment for a GI reason: 1.3% and 3.5%, versus 0.2%
• Severe GI reactions: 2.2% at 0.75 mg and 4.3% at 1.5 mg, versus 1.4%

Most events were mild to moderate [1]. In the 36-week AWARD-11 trial, nausea occurred in 13.4% of patients on 1.5 mg, 15.6% on 3 mg and 16.4% on 4.5 mg [1]. Over a median 5.4 years in REWIND, 47.4% of dulaglutide patients reported a GI adverse event versus 34.1% on placebo [2].

The label warns that gastrointestinal reactions, especially vomiting or diarrhea, can lead to volume depletion and acute kidney injury; most reported cases of acute kidney injury occurred in patients with such reactions. It advises monitoring renal function in patients reporting reactions that could lead to volume depletion, especially during initiation and dose escalation [1]. The label also states that Trulicity is not recommended in patients with severe gastroparesis [1].

Hypoglycemia depends on what else the patient takes

In a 26-week trial with metformin, glucose below 54 mg/dL occurred in 0% of patients receiving placebo, 0.3% receiving 0.75 mg, and 0.7% receiving 1.5 mg [1].

With a sulfonylurea or insulin the rates are higher. With glimepiride, glucose below 54 mg/dL occurred in 3.3% on 1.5 mg versus 0% on placebo [1]. In a 78-week trial with a sulfonylurea, it occurred in 20% on 0.75 mg and 21% on 1.5 mg, with severe hypoglycemia in 0% and 0.7% [1]. With insulin glargine, glucose below 54 mg/dL occurred in 14.7% on 1.5 mg versus 9.3% on placebo, and severe hypoglycemia in 0.7% versus 0% [1].

The label says to consider reducing the dose of an insulin secretagogue such as a sulfonylurea, or of insulin, when starting Trulicity, to lower hypoglycemia risk [1].

Cardiovascular risk reduction

For adults with type 2 diabetes who have established cardiovascular disease or multiple cardiovascular risk factors, the label includes an indication to reduce the risk of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke [1].

REWIND enrolled 9,901 adults aged 50 and older with type 2 diabetes and either a previous cardiovascular event or risk factors, 31.5% of whom had established cardiovascular disease; participants received dulaglutide 1.5 mg weekly or placebo, with a median follow-up of 5.4 years [2]. The primary composite endpoint occurred in 12.0% of the dulaglutide group versus 13.4% of the placebo group (hazard ratio 0.88, 95% CI 0.79 to 0.99; p=0.026). All-cause death was 10.8% versus 12.0% (hazard ratio 0.90, not significant) [2]. The label reports fatal or non-fatal stroke at 3.2% versus 4.1% (hazard ratio 0.76) [1]. Older adults were eligible, but these figures are the overall trial result rather than an age-specific result for patients in their seventies or eighties [2].

In SURPASS-CVOT, 13,165 adults with type 2 diabetes and atherosclerotic cardiovascular disease (mean age 64.1) received tirzepatide or dulaglutide 1.5 mg. Cardiovascular death, myocardial infarction or stroke occurred in 13.1% on dulaglutide versus 12.2% on tirzepatide (hazard ratio 0.92, 95.3% CI 0.83 to 1.01), meeting noninferiority but not superiority [5].

Kidney function

Dulaglutide is presumed to be degraded into amino acids by general protein catabolism, and renal or hepatic impairment has no clinically relevant effect on its exposure [1]. AWARD-7 randomized 577 adults with type 2 diabetes and stage 3 to 4 chronic kidney disease to dulaglutide 1.5 mg, dulaglutide 0.75 mg or insulin glargine, each with insulin lispro; at 26 weeks both dulaglutide doses were non-inferior to insulin glargine for HbA1c change, and eGFR and the urine albumin-to-creatinine ratio were secondary endpoints [6].

Other label warnings

• Thyroid C-cell tumors: dulaglutide caused dose-related thyroid C-cell tumors in rats; human relevance is unknown, and it is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2 [1]
• Acute pancreatitis: the label says to discontinue if pancreatitis is suspected [1]
• Serious hypersensitivity including anaphylaxis and angioedema: the label says to discontinue if one occurs [1]
• Diabetic retinopathy complications: reported in a cardiovascular outcomes trial; the label advises monitoring patients with a history [1]
• Acute gallbladder disease: the label says gallbladder studies are indicated if cholelithiasis or cholecystitis is suspected [1]
• Pulmonary aspiration during general anesthesia or deep sedation: reported with GLP-1 receptor agonists; the label says to instruct patients to inform healthcare providers of planned surgeries or procedures [1]

Label points that matter when care changes hands

• Trulicity is a once-weekly injection; the label lets the weekly day be changed if the last dose was 3 or more days before the new day [1]
• Missed dose: give it if at least 3 days (72 hours) remain before the next scheduled dose; otherwise skip it [1]
• With insulin, the label says to give Trulicity as a separate injection and never mix them; the same body region is acceptable but the injections should not be adjacent [1]
• If insulin or a sulfonylurea is co-prescribed, the label says to consider reducing their dose when starting Trulicity [1]
• The label says to train patients and caregivers on injection technique before starting, and that the solution should be clear and colorless and not used if particulate matter or coloration is seen [1]