Liraglutide Side Effects: Severity Distribution by Patient Phenotype

Adverse reactions in Saxenda adult trials (%) [1]

How the Labels Report Side-Effect Rates

The Saxenda label's adult safety table gives a single rate per reaction for all 3,384 liraglutide-treated patients, and its pediatric table a single rate for 125 adolescents [1]. The Victoza table gives rates by dose, 1.2 mg and 1.8 mg [2].

Frequency is not severity. Only a few label entries say how often a reaction was severe or ended treatment. Victoza reports severe gastrointestinal reactions in 4.4% of patients at 1.2 mg and 4.2% at 1.8 mg, versus 1.1% on placebo, and withdrawals for gastrointestinal reactions in 4.3% versus 0.5%, mostly during the first two to three months [2]. Saxenda reports that 9.8% of adults and 10.4% of adolescents stopped treatment because of an adverse reaction, versus 4.3% and 0% on placebo [1].

Adults on Saxenda 3 mg

Five placebo-controlled trials, 3,384 on Saxenda versus 1,941 on placebo, treatment up to 56 weeks [1]:

• Nausea 39.3% vs 13.8% [1]
• Diarrhea 20.9% vs 9.9% [1]
• Constipation 19.4% vs 8.5% [1]
• Vomiting 15.7% vs 3.9% [1]
• Headache 13.6% vs 12.6% [1]
• Injection site reaction 13.9% vs 10.5% [1]
• Dyspepsia 9.6% vs 2.7% [1]
• Fatigue 7.5% vs 4.6% [1]
• Dizziness 6.9% vs 5% [1]

About 68% versus 39% reported any gastrointestinal disorder, and the label notes that nausea declined as treatment continued [1]. Discontinuation for adverse reactions was 9.8% versus 4.3%, driven by nausea (2.9% vs 0.2%), vomiting (1.7% vs less than 0.1%) and diarrhea (1.4% vs 0%) [1].

Victoza: The Dose Comparison

Type 2 diabetes, pooled placebo-controlled trials (placebo N=661, 1.2 mg N=645, 1.8 mg N=1024) [2]:

• Nausea 5% / 18% / 20% [2]
• Diarrhea 4% / 10% / 12% [2]
• Vomiting 2% / 6% / 9% [2]
• Decreased appetite 1% / 10% / 9% [2]
• Constipation 1% / 5% / 5% [2]

Ages 12 to 17 on Saxenda

In the 56-week pediatric trial (125 liraglutide vs 126 placebo): nausea 42.4% vs 14.3%, vomiting 34.4% vs 4%, diarrhea 22.4% vs 14.3%, hypoglycemia below 70 mg/dL with symptoms 15.2% vs 4%, depression 4% vs 2.4%; 10.4% versus 0% stopped for adverse reactions [1].

Which Patients the Labels Do Single Out

• Personal or family history of medullary thyroid carcinoma or MEN 2: contraindicated [1].
• Severe gastroparesis: the Saxenda label says it is not recommended in these patients [1].
• Insulin or a sulfonylurea: hypoglycemia risk. Among adults with type 2 diabetes taking a sulfonylurea, glucose below 54 mg/dL occurred in 28.2% on Saxenda versus 12.7% on placebo, with sulfonylurea doses cut 50% at the start of the trial [1].
• Heart rate: mean resting increase of 2 to 3 bpm; a rise above 10 bpm at two consecutive visits in 34% versus 19% [1].
• Gallbladder: cholelithiasis 2.2% versus 0.8% and cholecystitis 0.8% versus 0.4% in Saxenda adult trials [1].

Does Severity Differ by Patient Phenotype?

The labels give frequency by dose or age group, plus how often gastrointestinal reactions were severe or led to stopping treatment [1][2]. The patient-specific cautions they state are the ones listed above.