Do you know 39% of adults in the world are overweight? One out of five children or adolescents is overweight. With a large number of individuals who are obese as well as diabetic, a medicine that can treat both conditions is the need of the time[1].

But unfortunately, there are only limited treatment options available. This is because not many weight loss drugs have been removed from the market due to side effects.
Liraglutide is already available in the market as Victoza® (indicated for treating type 2 diabetes mellitus). However, Saxenda contains higher doses of Liraglutide than Victoza®. Company Novo Nordisk, Inc markets Saxenda® injection.
This article will discuss the use of Liraglutide as a weight loss medication, including its introduction, mechanism of action, and side effects.

What is Saxenda injection?

Saxenda (Active ingredient: Liraglutide) is an injectable drug that belongs to the class glucagon-like peptide-1 receptor analogue. Manufactured by recombinant technology, Saxenda is 97% similar to its analog, GLP-1[3].
Saxenda is a weight loss drug that helps your body feel full for a longer duration after eating. This leads to overall less eating. Although Saxenda is not recommended for everyone, it helps you reach your goal and maintain a healthier weight[4].
The U.S. Food and Drug Administration (FDA) approved Liraglutide on December 23, 2014[3], as adjuvant therapy to treat chronic weight management. And it is the only drug approved by FDA in injectable form for weight loss.

Who should use Saxenda injection?

Liraglutide is used as an adjunct to a low-calorie diet and increased exercise for the treatment of chronic weight loss in
• Patients with a Body Mass Index (BMI) of ≥30 kg/ m² (obese)[5]
• Patients with a BMI between 27-29 kg/m² (overweight) with one or more weight-related comorbidities (such as insulin resistance, hypertension, dyslipidemia, sleep apnea, arthritis, hyperuricemia, gall bladder disease)[6]
• Children aged 12 years or greater with a bodyweight of 132 pounds (60 kg) or greater

Is Saxenda injection effective for weight loss?

Two factors have a major impact on your weight loss journey with Liraglutide. These factors are as follows:
1. How well do you tolerate Liraglutide?
2. Your adherence to a healthy lifestyle, including a low-calorie diet and exercise
You need to continue your healthy lifestyle during the whole Saxenda therapy. If you do not maintain it, you will get no results.
The long-term efficacy and safety profile of Saxenda has been well-established[7]. During clinical trials, patients on Saxenda show more weight loss than patients on placebo. Liraglutide is the first drug approved by FDA only for weight loss.

According to the guidelines of the American Diabetes Association and the American Association of Clinical Endocrinologists, Saxenda is an effective drug for obesity management. However, Liraglutide has limited efficacy, and some patients do not respond to the therapy[8].
Many of you would be questioning how do you know if Saxenda is working or not? If you lose 4% of your body weight on your follow-up appointment after 4 months, then Saxenda is working. But if there is no reduction of at least 1% in your BMI, discontinue the therapy.

How to use Saxenda injection for weight loss?

Your health care provider will counsel you on the dosage, time, administration, and side effects of Saxenda.
• Dose of Saxenda injection:
The starting dose of Saxenda is 0.6mg injected once a day. This dose will be maintained for at least one week. Your doctor then increases the dose by 0.6mg each week until you reach 3mg (recommended dose for Saxenda). Do not increase your dose further.

• What time is best to take Saxenda injection?
Saxenda injection is prescribed once a day. You can take your Saxenda dose at any time of the day. But try to take your daily dose at the same time each day.

• Prefilled pen
Saxenda comes in a pre-filled, dial-a-dose pen. The amount of medicine already loaded in pen; 18 mg of Liraglutide. Depending on the dose you dial, you can inject doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, and 3 mg. You can watch a step-to-step video on the manufacturer’s website.

• Injection site
Saxenda injection is administered subcutaneously (under the skin). It can be injected in front of your abdomen, the front of your thigh, or your upper arm. Your doctor or nurse will teach you the technique to inject the needle.

• In case of missed dose:
If your dose of Saxenda and the next dose is more than 12 hours away, take the dose as soon as you remember. But if there are less than 12 hours until the next dose, skip the dose. And continue your regimen as usual from the next day. Do not take an extra dose or doubled the dose on the following day.
If you missed your dose for consecutive three or more days, consult your health care provider to start your therapy anew.
To improve your compliance, try using a medication reminder. It can be an alarm, timer, or reminder app on your smartphone.

• In case of overdose:
If you overdose on Saxenda, call the help centre immediately and seek medical attention.

How Saxenda works?

Liraglutide (Brand name: Saxenda) is a glucagon-like peptide-1 (GLP-1) receptor agonist[9]. GLP-1 is a hormone form in the small intestine. It releases shortly after food intake. Physiologically, GLP-1 regulates appetite and calorie intake. It lowers blood glucose levels by two actions:
1. Stimulating the production of insulin, a pancreatic hormone that regulates blood sugar levels
2. Restricts the liver from releasing excess glucose

GLP-1 receptors are located in several areas of the brain that are known to regulate appetite. Liraglutide and other GLP-1 agonists also slow gastric emptying[3] that will keep you full for a longer period after eating. In other words, Liraglutide increases satiety and reduces hunger, resulting in less food intake, leading to weight loss[5].

Duration of therapy for weight loss:
The duration of therapy depends on your weight loss goal. Within 2-weeks of the therapy, your weight loss starts and continues to lose up to 9 to 12 months.

How long Saxenda does takes to work?

Well, you will feel the appetite-suppressing effects from the day you start therapy on Saxenda. You will feel satisfied for a longer time and less hungry in general.
However, Researchers are not confidents how long Saxenda therapy would be best for weight loss. But FDA recommends checking patients after 16 weeks (4 months) to see whether the drug is working or not. If the person loses 4% of their body weight, the therapy continues. But if not, then discontinue the therapy.
Important side effects of Saxenda injection:
The most common side effects of Saxenda injections are:
• Nausea
• Low blood sugar
• Diarrhoea
• Constipation
• Vomiting
• Headache
• Decreased appetite
• Dyspepsia
• Tiredness (fatigue)
• Dizziness
• Abdominal pain
• Injection site reaction such as redness, itching, or rash
• Increase levels of lipase enzyme in your blood.

Nausea is the first symptom you will experience when starting Saxenda therapy but decreases over time. In children, Saxenda injection can cause fever and gastroenteritis.
However, some rare serious adverse reactions[10] is observed in patients treated with Saxenda injections are:
Pancreatitis:
Saxenda causes inflammation of the pancreas[11], characterized by severe pain in the abdomen (your stomach area to your back) that will not go away. This abdominal pain may or may not be accompanied by vomiting.
Gallbladder problems:
In clinical trials, Saxenda cause gallbladder problem[12] in some patients. These issues include
• Gallstones
• Pain in your upper stomach
• Jaundice (yellowing of eyes or skin, especially the palm of your hand and sole of your feet)
• Fever
• Pale-coloured stool

Hypoglycemia:
Saxenda increases the risk of low blood sugar levels. This adverse effect occurs in:
• Patients who have type 2 diabetes and are currently on sulfonylureas or insulin[13]
• Children of age ≥12 years
Before starting Saxenda therapy, you should check your blood sugar and continue to monitor it during the therapy. The signs and symptoms of hypoglycemia are sweating, headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, and a fast heartbeat.
Kidney problems:
Saxenda injection causes nausea, vomiting, and diarrhoea (that do not go away), leading to dehydration. And severe dehydration can result in kidney failure[14]. Drinking plenty of fluids is recommended during therapy with Saxenda. It can reduce the risk of dehydration and kidney failure.
Accelerated heart rate:
Saxenda injection can increase your resting heart rate that continues over time. Your physician will check your heart rate before starting the therapy and continue to monitor until the therapy is complete. Food and Drug Administration (FDA) recommends discontinuation of Saxenda therapy in patients who experience a sustained increase in heart rate[6].
Hypersensitivity reactions:

Like most drugs, Saxenda can cause a serious allergic reaction in some patients. Contact your health care provider immediately in case of the following symptoms:
• Swelling of face, lips, tongue, or throat
• Fainting or feeling dizzy
• Very rapid heartbeat
• Problems breathing or swallowing
• Severe rash or itching.

Depression:
Patients on Saxenda therapy can develop depression that may be characterized by suicidal thoughts[15]. The symptoms include low mood, irritability, anger outbursts, and constant sadness, hopelessness, and tearfulness.
Box warning of Liraglutide:
Liraglutide (Saxenda) has a boxed warning from FDA. Liraglutide is contraindicated in patients with multiple endocrine neoplasia type 2 (MEN 2). Liraglutide causes C-cell thyroid tumours in both genders of mice and rats. However, it is not proven that Saxenda causes C-cell thyroid tumours, including medullary thyroid carcinoma (MTC) in humans.

Who should not use Saxenda injection for weight loss?
Although the Saxenda is effective for weight loss, you should not use it if:
• You are allergic to Liraglutide.
• You are suffering from Multiple endocrine neoplasia type 2 (MEN 2) – tumours in your glands.
• You have a medical or family history of medullary thyroid carcinoma (MTC) – a type of thyroid cancer.
• Have diabetic ketoacidosis
• You are currently on insulin or other Liraglutide drugs (albiglutide, dulaglutide, exenatide, Bydureon, Tanzeum, and Trulicity).
• You are pregnant. Saxenda is not safe for the unborn baby.
• Saxenda is not approved for weight loss in children below 12 years of age. Also, it is not approved for use in patients younger than 18 years.
• You breastfeed your baby as it is unknown whether Saxenda excretes in milk or not.

Before starting Saxenda therapy, consult your health care provider if you have any of the following:
• Stomach problems causing indigestion
• Kidney or liver disease
• High-level triglycerides in the blood)
• Heart problems because the effects of Saxenda on cardiovascular morbidity and mortality are not known yet.
• History of pancreatitis or gallbladder problems
• History of depression or suicidal thoughts.
Precautions while using Saxenda injection:

What should you avoid while using Saxenda injection?
As Saxenda is taken as an injection, you should avoid sharing needles or pens with others. Do not other weight loss medications, appetite suppressants, and insulin during Saxenda therapy.

How do other drugs affect the efficacy of Saxenda injection?

Saxenda slows gastric emptying. Hence, it can interfere with the absorption of oral medications. Following drugs should not use along with Saxenda therapy:
• Insulin and other diabetic medicines – when Liraglutide is used along with insulin or other oral diabetic medications, the risk of hypoglycemia can increase by many folds. That’s why this combination must be avoided at all costs.
• Drugs that slow gastric motility – Anticholinergic and opioids that reduce gastric motility can decrease gastric emptying of Liraglutide.
• Narrow therapeutic index drugs – Liraglutide slows gastric emptying and alters the absorption of these drugs that can be harmful.
Comparison with other drugs: Saxenda is not compared directly with other approved weight loss medications. But as other weight-loss drugs are taken orally, they are more convenient to administer. However, Saxenda is effective in case of obesity accompanied by one or more comorbidities.

Final thoughts: Saxenda is used for the treatment of chronic weight management, in addition to exercise and a low-calorie diet. But always consult your health care provider to ensure the information displayed on this page applies to your circumstances.

References:
1. Onge, E.S., et al., Liraglutide (Saxenda®) as a Treatment for Obesity. 2016. 7(04): p. 227.
2. Bray, G.A., Medical Consequences of Obesity. The Journal of Clinical Endocrinology & Metabolism, 2004. 89(6): p. 2583-2589.
3. T-Cells, C., Novo Nordisk Receives FDA Approval of Saxenda®(Liraglutide) injection 3 mg Label Update Including Long-Term Safety and Efficacy Data from 3-Year Trial.
4. Halawi, H., et al., Effects of Liraglutide on weight, satiation, and gastric functions in obesity: a randomized, placebo-controlled pilot trial. 2017. 2(12): p. 890-899.
5. Lambert, L.J.J.o.E., Metabolism and D.o.S. Africa, Focus on Saxenda® solution for injection. 2021. 25(1): p. 8-10.
6. Aschenbrenner, D.S.J.A.T.A.J.o.N., New Trade Name and New Indication for Liraglutide. 2015. 115(4): p. 22-23.
7. TO, T., The long-term efficacy and safety profile of Saxenda® has been well established.
8. Tan, T. Novel therapies for obesity-an update. in Endocrine Abstracts. 2018. Bioscientifica.
9. Jacobsen, L.V., et al., Liraglutide in type 2 diabetes mellitus: clinical pharmacokinetics and pharmacodynamics. 2016. 55(6): p. 657-672.
10. Plourde, G.J.C.R.i.D. and Endocrinology, Saxenda in the management of obesity in a type 2 diabetes mellitus patient: a case report. 2018. 1(1): p. 1-7.
11. Brewer, F., Liraglutide (Victoza/Saxenda) for Diabetes & Weight Loss.
12. Whitten, J.S.J.A.f.p., Liraglutide (Saxenda) for weight loss. 2016. 94(2): p. 161-166.
13. Davies, M.J., et al., Efficacy of Liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. 2015. 314(7): p. 687-699.
14. Wong, N. and Y. Cooperman, Does taking Victoza help with weight loss?
15. Elliott, W.T.J.I.M.A., Liraglutide Injection (Saxenda®). 2015. 37(11).