Saxenda (Liraglutide 3 mg) Safety in Adults 65 and Older

Does the label exclude older adults?

No. Saxenda is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2), and in patients with a serious hypersensitivity reaction to liraglutide or to any excipient [1]. Age is not part of either criterion. The label's adult schedule is a single one: 0.6 mg once daily for one week, then 1.2 mg, 1.8 mg and 2.4 mg at weekly intervals, reaching 3 mg daily from week 5 [1]. The 3 mg dose is the recommended adult dose and the lower doses are for titration only [1].

The indication is drawn by body weight and comorbidity, not age: adults with obesity, or adults with overweight plus at least one weight-related comorbid condition, used alongside a reduced-calorie diet and more physical activity [1].

Who produced the safety numbers

Saxenda was evaluated in five double-blind, placebo-controlled adult trials: 3,384 patients on Saxenda and 1,941 on placebo, treatment up to 56 weeks at 3 mg daily [1]. Mean age at baseline was 47 years; 71% were women, 39% had hypertension, 15% had type 2 diabetes, 34% had dyslipidemia and 9% had cardiovascular disease [1].

The weight-management trial behind the headline results, SCALE Obesity and Prediabetes, randomized 3,731 adults without diabetes (2,487 to liraglutide 3.0 mg and 1,244 to placebo). Its mean age was 45.1 years, with a standard deviation of 12.0 [2]. At week 56, mean weight loss was 8.4 kg with liraglutide 3.0 mg and 2.8 kg with placebo, a difference of 5.6 kg [2].

Gastrointestinal reactions and the kidney warning

In the pooled adult trials, nausea occurred in 39.3% of Saxenda-treated patients versus 13.8% on placebo, diarrhea in 20.9% versus 9.9%, constipation in 19.4% versus 8.5% and vomiting in 15.7% versus 3.9% [1]. About 68% versus 39% reported some gastrointestinal disorder, and nausea became less frequent as treatment continued [1]. Adverse reactions led to discontinuation in 9.8% versus 4.3%, with nausea the most common reason (2.9% versus 0.2%) [1].

Two Warnings and Precautions items concern volume loss and the gut. The first is acute kidney injury due to volume depletion, where the label says to monitor renal function in patients reporting adverse reactions that could lead to volume depletion. The second is severe gastrointestinal reactions, with the statement that Saxenda is not recommended in patients with severe gastroparesis [1].

Heart rate

Resting heart rate rose by a mean of 2 to 3 beats per minute on Saxenda compared with placebo [1]. More Saxenda-treated patients had changes from baseline of more than 10 bpm at two consecutive visits (34% versus 19%) and more than 20 bpm (5% versus 2%); at least one reading above 100 bpm was recorded in 6% versus 4%, and tachycardia was reported as an adverse reaction in 0.6% versus 0.1% [1]. Continuous 24-hour monitoring in a clinical pharmacology trial showed a heart rate 4 to 9 bpm higher than with placebo [1]. The label says to monitor heart rate at regular intervals [1].

Dizziness and falls

Dizziness was reported by 6.9% of Saxenda-treated adults versus 5.0% on placebo [1]. Falls are not listed in the label's adult adverse reaction table, which lists reactions reported by at least 2% of Saxenda-treated patients and more frequently than with placebo [1].

Hypoglycemia when insulin or a sulfonylurea is also used

Hypoglycemia is a Warnings and Precautions item, not a boxed warning; the boxed warning is the thyroid C-cell tumor risk [1]. In adults with type 2 diabetes taking a sulfonylurea, glucose below 54 mg/dL with or without symptoms occurred in 28.2% of Saxenda-treated patients versus 12.7% on placebo, in a trial where sulfonylurea doses were reduced by 50% at the start per protocol [1]. The label says the risk may be lowered by reducing the dose of the sulfonylurea or insulin, and asks that patients on these drugs be told the signs and symptoms of hypoglycemia [1].

Gallbladder, pancreatitis and the thyroid boxed warning

Cholelithiasis was reported in 2.2% of Saxenda-treated adults versus 0.8% on placebo and cholecystitis in 0.8% versus 0.4%; most of those patients required cholecystectomy, and the excess over placebo remained after accounting for the degree of weight loss [1]. Acute pancreatitis is among the warnings, and the label says to discontinue Saxenda if pancreatitis is suspected [1]. The boxed warning covers thyroid C-cell tumors in rats and mice, states that human relevance is unknown, and contraindicates use in patients with a personal or family history of MTC or MEN 2 [1]. The label also warns about pulmonary aspiration during general anesthesia or deep sedation and says patients should be instructed to inform healthcare providers of planned procedures [1].

Titration and stopping rules in the label

The schedule is 0.6 mg in week 1, 1.2 mg in week 2, 1.8 mg in week 3, 2.4 mg in week 4, and 3 mg from week 5 onward [1]. If a dose increase is not tolerated during escalation, the label says to consider delaying escalation for approximately one additional week [1]. It also says to discontinue Saxenda if the 3 mg dose cannot be tolerated [1]. If more than 3 days have passed since the last dose, the label says to restart at 0.6 mg and follow the escalation schedule again [1]. Body weight is evaluated 16 weeks after starting, and the label says to discontinue Saxenda if less than 4% of baseline body weight has been lost [1].

Oral medications and delayed gastric emptying

Saxenda delays gastric emptying and may affect absorption of oral medicines. In clinical pharmacology trials, it did not affect absorption of the tested oral medicines to a clinically relevant degree; the label advises monitoring for consequences of delayed absorption [1]. The interaction section treats oral medicines as a class rather than naming individual drugs, and the label gives no instruction to switch or add contraception [1].

What the tables do not show for adults 65 and older

The label's adverse reaction tables report rates for all adults combined, not by age group, and the adult trials averaged age 47 [1]. An older patient is therefore being treated on overall adult data, with the GI, kidney, heart-rate and hypoglycemia warnings above as the label's stated cautions.