- ACRONYMS AND DEFINITIONS
- BMI - Body mass index
- DM - Diabetes Mellitus
- GI - Gastrointestinal
- Thyroid C-cell tumor - same as thyroid medullary tumor
- DRUGS IN CLASS
- Saxenda® (liraglutide)
- Saxenda (liraglutide) is a GLP-1 analog
- GLP-1 analogs, including liraglutide, are approved for the treatment of Type 2 diabetes - see GLP-1 analogs in diabetes
- In diabetes studies, GLP-1 analogs caused a small amount of weight loss
- This observation led to the development of Saxenda for weight loss
- Liraglutide is marketed under the name Victoza® for Type 2 diabetes treatment
- MECHANISM OF ACTION
- GLP-1 analogs
- GLP-1 stands for "Glucagon-Like Peptide-1"
- GLP-1 is a hormone secreted into the bloodstream by special cells in the intestine
- GLP-1 is a physiological regulator of appetite and calorie intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation
- In animal studies, peripheral administration of liraglutide resulted in the presence of liraglutide in specific brain regions regulating appetite, including the hypothalamus
- The exact mechanism by which liraglutide regulates appetite is unknown
- FDA-APPROVED INDICATION
- Saxenda is FDA-approved for the following indications:
- Weight loss in adults with BMI ≥ 30
- Weight loss in adults with BMI ≥ 27 in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia)
- EFFECTIVENESS
- WEIGHT LOSS
- Liraglutide has been studied for weight loss in several randomized placebo-controlled trials
| 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 | |
| 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) | |
| 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 | |
- StraightHealthcare analysis:
- When prescribing Saxenda for one year, providers can expect the following:
- About 28% of patients will discontinue the drug
- On average, a 233-pound person will lose about 10 pounds more on Saxenda than if they were not taking it
- SIDE EFFECTS
- GASTROINTESTINAL (GI) SIDE EFFECTS
- 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 effect | Saxenda (% of patients) |
Placebo (% of patients) |
|---|---|---|
| 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
- Injection site reactions including redness, itching, and rash were reported in 14% of Saxenda-treated patients (10.5% of placebo-treated patients reported reactions)
- LIRAGLUTIDE ANTIBODIES
- 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
- StraightHealthcare analysis:
- 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 (INFLAMMATION OF THE PANCREAS)
- Pancreatitis is a condition where the pancreas becomes inflamed
- Pancreatitis is a painful, life-threatening condition
- 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
- StraightHealthcare analysis:
- In diabetes trials, the FDA reviewed a large amount of information regarding GLP-1 analogs and pancreatitis. No definitive link was found. See GLP-1 analogs and pancreatitis for more.
- DECREASED KIDNEY FUNCTION
- 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.
- StraightHealthcare analysis:
- Saxenda does not appear to directly affect kidney function
- Saxenda may indirectly affect kidney function if GI side effects lead to dehydration
- THYROID CANCER
- In toxicology studies, liraglutide was found to cause malignant and benign thyroid C-cell tumors (also called medullary thyroid cancer) in rats and mice
- It is unknown if liraglutide increases the risk of thyroid cancer in humans
- See GLP-1 analogs and thyroid cancer for more information
- GALLBLADDER DISEASE
- In trials, 1.5% of Saxenda-treated patients reported cholelithiasis vs 0.5% of placebo-treated patients
- In trials, 0.6% of Saxenda-treated patients reported cholecystitis vs 0.2% of placebo-treated patients
- Rapid weight loss can increase the risk of cholelithiasis, however, the risk was still elevated in Saxenda-treated patients after accounting for weight loss
- HEART RATE INCREASE
- In trials, Saxenda-treated patients had an average increase in resting heart rate of 2 - 3 beats per minute when compared to placebo
- The clinical significance of this effect is unknown
- BREAST CANCER
- In trials, 0.6% of 2379 Saxenda-treated patients developed breast cancer compared to 0.2% of 1300 placebo-treated patients. The incidence of breast cancer was too low to determine causality.
- An observational study published in the BMJ in 2016 found no increased risk of breast cancer among GLP-1 analog users when compared to DPP-4 inhibitor users (HR 1.40 (95%CI [0.91 to 2.16]). The average follow-up in the study was 3.5 years. [PubMed abstract]
- LIPASE INCREASES
- In trials, lipase increases were seen in 5.3% of Saxenda-treated patients and 2.2% of placebo-treated patients
- Lipase levels ≥ 3 X ULN were seen in 2.1% of Saxenda-treated patients and 1% of placebo-treated patients
- CALCITONIN INCREASES
- Calcitonin levels ≥ 2 X ULN were seen in 1.2% of Saxenda-treated patients and 0.6% of placebo-treated patients
- CONTRAINDICATIONS
- Known hypersensitivity
- Pregnancy
- Personal or family history of medullary thyroid carcinoma (MTC)
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- PRECAUTIONS
- KIDNEY DISEASE
- Saxenda has not been studied extensively in kidney disease. Use with caution.
- Manufacturer makes no dosage recommendations
- LIVER DISEASE
- Saxenda has not been studied extensively in liver disease. Use with caution.
- Manufacturer makes no dosage recommendations
- DIABETES
- Diabetics who are taking diabetes medications (particularly sulfonylureas and meglitinides) may be at increased risk of hypoglycemia when taking liraglutide
- Diabetics should monitor blood sugars closely when starting liraglutide
- Diabetics may need to lower their dose of sulfonylurea or meglitinide when starting Saxenda
- The manufacturer states that Saxenda should not be used in diabetics who are using insulin
- STOMACH DISORDERS
- Stomach disorders that slow gastric emptying (ex. diabetic gastroparesis) may be worsened by Saxenda
- Caution should be used in these patients
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- HIGH ALERT INTERACTIONS
- Insulin
- Saxenda should not be used in diabetics who are using insulin because of the high risk of hypoglycemia
- Diabetes medications
- When Saxenda is taken with diabetes medications, the risk for low blood sugar is increased
- High-risk medications include sulfonylureas and meglitinides
- Diabetics may need to lower their dose of sulfonylurea or meglitinide when starting Saxenda
- METABOLISM AND ELIMINATION
- Saxenda does not undergo significant liver metabolism
- OTHER
- Stomach (gastric) emptying
- 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
- Saxenda slows the process of stomach emptying
- Since most medications are absorbed in the small intestine, slowing of stomach emptying by Saxenda can affect the absorption of medications
- In many cases, the overall effect on the drug's therapeutic action is not significant
- The large number of possible interaction has not been studied extensively
- The following types of medications may be more susceptible to a significant interaction:
- Oral contraceptives
- Antibiotics
- Antibiotics require rapid absorption to achieve their desired therapeutic effect
- Saxenda may alter their absorption
- Antibiotics should be taken at least 1 hour before Saxenda
- Drugs with a narrow therapeutic index
- Drugs with narrow therapeutic index may be affected by Saxenda
- Taking these drugs at least 1 hour before Saxenda may help prevent an interaction
- Drugs with a narrow therapeutic index:
- Carbamazepine (Tegretol®)
- Cyclosporine (Neoral®)
- Digoxin
- Levothyroxine (Synthroid®)
- Lithium
- Phenytoin (Dilantin®)
- Tacrolimus (Prograf®)
- Theophylline (Theo-24®)
- Warfarin (Coumadin®) [9]
- Drugs that alter gastrointestinal motility
- Drugs that slow gastrointestinal motility may potentiate the gastric-slowing effects of Saxenda
- Examples include:
- Anticholinergic medications
- Opiate pain medications (hydrocodone, morphine, etc.)
- DOSING
- DOSAGE FORM
- Saxenda comes in a 3ml pen that contains 6 mg/ml of liraglutide
- The pen can be dialed to doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg
- The pens come in packages that contain 3 pens (18 doses at 3 mg) or 5 pens (30 doses at 3 mg)
- DOSING
- Saxenda is injected once daily
- Saxenda is injected subcutaneously in the abdomen, thigh, or upper arm
- Saxenda can be injected at any time during the day without regard to meals or food
- Initial titration schedule
- Dose is titrated to limit GI side effects
- Consider delaying escalation for 1 week if patient cannot tolerate increase
| 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 |
- Recommended maintenance dose
- 3 mg once daily
- OTHER
- Efficacy of doses < 3 mg a day has not been established
- Evaluate weight loss at 16 weeks. Discontinue Saxenda if weight loss is < 4% of baseline weight.
- If dose is missed, resume as prescribed at the next scheduled dose
- If more than 3 days elapse since the last dose, restart Saxenda at 0.6 mg and use the titration schedule above
- Saxenda solution should be clear and colorless without particles. Otherwise, it should be discarded.
- STORAGE
- UNOPENED PENS
- Store in refrigerator
- Good until expiration date
- PUNCTURED/USED PENS
- May be stored in refrigerator or room temperature
- Good for 30 days
- NEEDLES
- Compatible with NovoFine® and NovoTwist® disposable pen needles up to a length of 8mm
- LONG-TERM SAFETY
- GLP-1 analogs, including Saxenda, are relatively new medications
- Saxenda was FDA-approved in DEC 2014
- There is no long-term safety information for Saxenda
- GENERIC AVAILABILITY
- Generics
- None currently
- Other patent expirations:
| DRUG | PATENT EXPIRES |
|---|---|
| Saxenda® (liraglutide) | AUG 2017 |
- NOTE: Drug companies typically file multiple patents on their drugs in order to protect them from competition. The patent expiration listed here is the date that the earliest patent on the drug expires (accounting for pediatric exclusivity). Because drug companies use numerous techniques to extend the life of their patents, it does not necessarily mean a generic will become available around this date.
- BIBLIOGRAPHY
- What is PMID?
- PI = Manufacturer's Package Insert
- # PMID
- 1 - Saxenda PI
- 2 - Saxenda NDA
- 3 - 26284720 - SCALES study
- 4 - 28237263 - 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet (2017)