SAXENDA® (LIRAGLUTIDE)



















  • Average baseline weight was 233 pounds (106 kg)
  • Average baseline BMI was 38
  • Dropout rate: liraglutide 28% | placebo 35.6%
  • Reference [1,2]
Liraglutide (Lir) vs placebo in a 56-week weight loss trial
Placebo (N=1244) Lir 3 mg daily (N=2487)
Weight loss (%)
(average % change from baseline at 56 weeks)
3% 7.4%
Weight loss (pounds)
(average pounds lost at 56 weeks)
7 17

  • Average baseline weight was 238 pounds (108 kg)
  • Average baseline BMI was 39
  • Dropout rate: liraglutide 47% | placebo 55%
  • Reference [4]
Liraglutide (Lir) vs placebo for 3 years in prediabetics
Placebo (N=738) Lir 3 mg daily (N=1472)
Weight loss (%)
(average % change from baseline at 3 years)
1.9% 6.1%
Weight loss lbs (kg)
(average pounds lost at 3 years)
4.4 lbs (2 kg) 14.3 lbs (6.5 kg)

  • Average baseline weight was 233 pounds (106 kg)
  • Average baseline BMI was 37
  • Dropout rate: liraglutide 3 mg - 23% | liraglutide 1.8 mg - 22% | placebo - 44%
  • Reference [3]
Liraglutide (Lir) vs placebo for 56 weeks in overweight diabetics
Placebo (N=212) Lir 1.8 mg daily (N=211) Lir 3 mg daily (N=423)
Weight loss (%)
(average % change from baseline at 56 weeks)
2% 4.7% 6%
Weight loss (pounds)
(average pounds lost at 56 weeks)
4.8 11 14




Gastrointestinal (GI) side effects
Overview
  • Gastrointestinal side effects are the most common side effects with Saxenda
  • GI side effects likely contribute to some degree to Saxenda's weight-loss properties
  • Side effects reported in placebo-controlled trials are presented in the table below

  • Reference [1]
Side effect Saxenda Placebo
Nausea 39% 14%
Diarrhea 21% 10%
Constipation 19.4% 8.5%
Vomiting 15.7% 3.9%
Upset stomach 9.6% 2.7%
Abdominal pain 5.4% 3.1%
GERD 4.7% 1.7%
Burping 4.5% 0.2%
Flatulence 4% 2.5%


Injection site reactions

Hypersensitivity reactions

Liraglutide antibodies
Overview
  • Liraglutide has the potential to induce an immune response
  • The immune response can lead to the production of antibodies against liraglutide
  • In trials, 2.8% of patients treated with liraglutide developed anti-liraglutide antibodies (1505 patients were tested)
  • In vitro studies showed that 43% of these antibodies had a neutralizing effect
Summary
  • It is not uncommon for injectable biologic drugs to induce antibodies (insulin is known for this)
  • The overall significance of this effect with liraglutide is unknown
  • Based on available evidence, a small percentage of liraglutide patients (1.2%) may experience a loss of effect if antibodies develop

Pancreatitis
Overview
  • Pancreatitis is a painful condition where the pancreas becomes inflamed. Severe pancreatitis can be life-threatening.
  • In clinical trials, acute pancreatitis was confirmed in 0.3% of 3291 Saxenda-treated patients and 0.1% of 1843 placebo-treated patients
  • The incidence of pancreatitis was too low to determine causality
Summary
  • The FDA reviewed a large amount of information regarding GLP-1 analogs and pancreatitis in diabetes trials and came to the conclusion that no definitive link could be proven. See GLP-1 analogs and pancreatitis for more.

Decreased kidney function
Overview
  • In patients receiving Saxenda, decreased kidney function has been reported
  • The majority of these cases occurred in patients who were experiencing gastrointestinal side effects. GI side effects can lead to dehydration which affects kidney function.
Summary
  • Saxenda does not appear to directly affect kidney function
  • Saxenda may indirectly affect kidney function if GI side effects lead to dehydration

Thyroid cancer

Gallbladder disease

Heart rate increase

Breast cancer

Lipase increases

Calcitonin increases






Kidney disease

Liver disease

Diabetes

Stomach disorders


Liraglutide (Saxenda®)

  • Diabetes medications - When Saxenda is taken with diabetes medications, the risk for low blood sugar is increased. High-risk medications include sulfonylureas, meglitinides, and insulin. Diabetics should watch their blood sugars closely when starting Saxenda and make adjustments if necessary. See GLP-1 analog blood sugar effects for a review of the blood sugar-lowering effects of liraglutide.
  • Drugs affected by decreased gastric emptying - see gastric emptying below
  • Drugs that alter gastrointestinal motility - Drugs that slow gastrointestinal motility may potentiate the gastric-slowing effects of GLP-1 analogs
  • Insulin - Saxenda should not be used in diabetics who are using insulin because of the high risk of hypoglycemia

Gastric emptying
Overview
  • When a person consumes food or medications, they are partially digested in the stomach
  • The stomach then "empties" food and medications into the small intestine
  • GLP-1 analogs slow the process of stomach emptying
  • Since most medications are absorbed in the small intestine, slowing of stomach emptying by GLP-1 analogs may affect the absorption of some medications
  • In many cases, the overall effect on the drug's therapeutic effect is not significant
  • The large number of possible interaction has not been studied extensively
  • The effect of the medications listed below may be altered by decreased gastric emptying caused by GLP-1 analogs
Antibiotics
  • Antibiotics require rapid absorption to achieve their desired therapeutic effect
  • GLP-1 analogs may alter their absorption
  • Antibiotics should be taken at least 1 hour before GLP-1 analogs
Drugs with a narrow therapeutic index
  • Drugs with narrow therapeutic index may be affected by GLP-1 analogs
  • Taking these drugs at least 1 hour before GLP-1 analogs may help prevent an interaction

Metabolism and clearance





Saxenda titration schedule
Week Saxenda dose
1 0.6 mg once daily
2 1.2 mg once daily
3 1.8 mg once daily
4 2.4 mg once daily
5 and on 3 mg once daily
  • Dose is titrated to limit GI side effects
  • Consider delaying escalation for 1 week if patient cannot tolerate increase