Liraglutide (SAXENDA): The Wrong Choice for Weight Loss

In 2014, the Food and Drug Administration (FDA) approved the drug liraglutide, which had been marketed for treatment of type 2 diabetes under the brand name VICTOZA, for a new use: weight loss.[1] The much higher-dose weight-loss version of this drug is marketed under a separate brand name: SAXENDA.

Public Citizen unsuccessfully petitioned the FDA in 2012 to ban liraglutide as a diabetes treatment because the drug offers no benefit over other diabetes treatments and increases the risk of thyroid cancer, pancreatitis and other serious adverse effects.[2]

The high-dose version of liraglutide that has been approved for weight loss also offers minimal benefits and can cause more of the same dangerous adverse events as the lower-dose form. Public Citizen’s Health Research Group therefore recommends that patients not use this dangerous drug and instead stick to the existing gold-standard nondrug treatment for overweight and obese adults who wish to achieve better health: diet and exercise.

Raising the dose on a toxic drug

Liraglutide was first approved by the FDA in 2010 as a treatment for type 2 diabetes at a dosage of up to 1.8 milligrams (mg) per day.[3] The drug, which is injected under the skin, was not originally approved for weight loss. However, clinical trials testing the drug for diabetes revealed that while on the drug, some research subjects did lose weight.[4] This discovery was not surprising, given that some of the drug’s most common adverse effects were nausea, vomiting and diarrhea.[5] The drug also slows the rate at which food empties from the stomach.

Before approving a drug for weight loss, the FDA generally requires that such drugs be compared with placebo in clinical trials that last at least one year and satisfy criteria set by the agency for what it considers to be clinically meaningful weight loss.[6] After testing several doses of liraglutide for up to one year to assess weightloss effects, the drug’s manufacturer, Novo Nordisk, determined that a much higher dosage of 3 mg per day was needed to meet the FDA’s standards for approving a weight-loss drug. This higher-dose version was given a new brand name: Saxenda.[7]

In clinical testing, the higher-dose liraglutide did meet the FDA’s effectiveness criteria for a weight-loss drug. But to keep the weight off, patients had to continue taking the drug. Subjects who stopped taking the drug at the end of the year gained back more than 2% of their weight, on average, in just 12 weeks.[8]

“The thought of food makes me want to throw up”

As with the clinical trials of liraglutide for diabetes, rates of gastrointestinal adverse effects were high in the liraglutide weight-loss trials: Nearly seven out of 10 subjects receiving liraglutide experienced some form of gastrointestinal problem, most often nausea, diarrhea, constipation, vomiting or indigestion, compared with only four out of 10 placebo-treated subjects.[9] This proved to be a very uncomfortable way to lose weight, and about 6% of subjects taking liraglutide withdrew from the weight-loss trials due to gastrointestinal adverse events, compared with only 1% of placebo-treated subjects.[10]

Many patients taking liraglutide for both diabetes and weight loss in the real world have quit after coming to the same conclusion. Some have gone online to slam the drug in scathing reviews. As one woman posted on the website AskaPatient.com regarding use of the drug for borderline diabetes and weight loss:

“I am nauseated all the time, and my stomach is tender and bloated... The thought of food makes me want to throw up; if you can’t eat, then of course you’re going to lose weight... this just isn’t the way I want to do it.”[11]

Dangerous adverse effects

Although many adverse effects of liraglutide produce only temporary discomfort, a few are more serious. Liraglutide carries a black-box warning about the drug causing thyroid tumors in mice and rats.[12] This warning further notes that the drug should never be used by patients who have a personal or family history of medullary thyroid cancer or by patients with a hereditary condition called multiple endocrine neoplasia syndrome type 2, which predisposes patients to cancer of the thyroid, parathyroid and adrenal glands.

Severe vomiting caused by liraglutide can lead to dehydration and kidney impairment, which in some cases may require hemodialysis.[13] In clinical trials, the drug also quadrupled the rate of pancreatitis, inflammation of the pancreas that can be life-threatening.[14]

Two out of every 100 subjects taking liraglutide for weight loss in clinical trials also experienced gallstones or related disorders, compared with only one out of 100 placebo-treated subjects. These problems also tended to be more severe than those that occurred in the placebo group, leading to more frequent withdrawals from the trials.[15] Some of this extra risk can be explained by the fact that losing weight quickly can increase a person’s chances of getting a gallstone.[16] But some of the risk was due to the drug itself: Even when comparing subjects who lost the same amount of weight, the rates of gallstones were higher among subjects taking liraglutide than in those taking a placebo.[17]

Risk of birth defects is another potential concern, as the drug is likely to be used by women who are sexually active and young enough to have children. Birth defects and early loss of pregnancy were observed in studies of rats and rabbits when the animals were exposed to liraglutide at doses even lower than are used in patients with diabetes.[18] When high-dose liraglutide was tested for weight loss in clinical trials, rates of miscarriage (spontaneous abortion) were twice as high among subjects taking liraglutide as in those taking a placebo, even though the women had stopped taking the drug after they realized they were pregnant.[19]

What You Can Do

We recommend that you do not use liraglutide for weight loss or for diabetes, as the drug is minimally effective and has many dangerous adverse effects, which are even more frequent with the higher-dose weight-loss version.

There is currently no medication that can be used safely to achieve weight loss effortlessly and without dangerous adverse effects. Rather than focus on losing weight by turning to risky drugs, overweight and obese adults seeking to achieve better health should make reasonable and sustainable changes to their lifestyle, such as eating a healthy diet and getting regular exercise.

Healthy eating and exercise may not guarantee dramatic long-term weight loss, but they remain by far the safest option for people seeking to lose weight in a healthy, sustainable way.
 

References

[1] Food and Drug Administration. FDA approves weight-management drug Saxenda. December 23, 2014. https://wayback.archive-it.org/7993/20170111160832/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427913.htm. Accessed September 14, 2020.

[2] Public Citizen. Petition to ban diabetes drug liraglutide (Victoza). April 19, 2012. https://www.citizen.org/article/petition-to-ban-diabetes-drug-liraglutide-victoza/. Accessed September 14, 2020.

[3] Novo Nordisk. Label: liraglutide (Victoza). August 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022341s035lbl.pdf. Accessed September 14, 2020.

[4] Ibid.

[5] Ibid.

[6] Food and Drug Administration. Draft guidance for Industry: Developing products for weight management (revision 1). February 2007. https://www.fda.gov/media/71252/download. Accessed September 14, 2020.

[7] Food and Drug Administration. FDA briefing document: NDA 206321; Liraglutide injection, 3 mg; Sponsor: Novo Nordisk; Endocrinologic and Metabolic Drugs Advisory Committee. September 11, 2014. https://wayback.archive-it.org/7993/20170405215615/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf. Accessed September 14, 2020.

[8] Ibid.

[9] Ibid.

[10] Ibid.

[11] Ask a Patient. Drug ratings for VICTOZA. https://www.askapatient.com/viewrating.asp?drug=22341&name=VICTOZA&sort=dateadded&page=9. Accessed September 14, 2020.

[12] Novo Nordisk. Label: liraglutide (Saxenda). March 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206321s011lbl.pdf. Accessed September 14, 2020.

[13] Ibid.

[14] Food and Drug Administration. FDA briefing document: NDA 206321; Liraglutide injection, 3 mg; Sponsor: Novo Nordisk; Endocrinologic and Metabolic Drugs Advisory Committee. September 11, 2014. https://wayback.archive-it.org/7993/20170405215615/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf. Accessed September 14, 2020.

[15] Ibid.

[16] National Institute of Diabetes and Digestive Kidney Disease. Dieting & gallstones. November 2017. https://www.niddk.nih.gov/health-information/digestive-diseases/gallstones/dieting. Accessed September 14, 2020.

[17] Food and Drug Administration. FDA briefing document: NDA 206321; Liraglutide injection, 3 mg; Sponsor: Novo Nordisk; Endocrinologic and Metabolic Drugs Advisory Committee. September 11, 2014. https://wayback.archive-it.org/7993/20170405215615/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf. Accessed September 14, 2020.

[18] Public Citizen. Petition to ban diabetes drug liraglutide (Victoza). April 19, 2012. https://www.citizen.org/article/petition-to-ban-diabetes-drug-liraglutide-victoza/. Accessed September 14, 2020.

[19] Food and Drug Administration. FDA briefing document: NDA 206321; Liraglutide injection, 3 mg; Sponsor: Novo Nordisk; Endocrinologic and Metabolic Drugs Advisory Committee. September 11, 2014. https://wayback.archive-it.org/7993/20170405215615/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf. Accessed September 14, 2020.