Liraglutide (SAXENDA) for Weight Loss

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

In the past, the FDA rejected Public Citizen’s petition 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 side effects.[3]

The high-dose version of liraglutide that has been approved for weight loss also offers minimal benefits and can cause the same dangerous adverse events. Public Citizen's Health Research Group therefore recommends that patients not use this dangerous drug and 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 of a toxic drug

Liraglutide was first approved by the FDA in January 2010, at a dose of up to 1.8 milligrams (mg) per day as a treatment for Type 2 diabetes.[4],[5] The drug, which is injected under the skin, originally was not approved for weight loss. However, clinical testing for diabetes revealed that while on the drug, some research subjects did lose weight.[6] This discovery was not surprising, given that some of the drug’s most common side effects were nausea, vomiting and diarrhea.[7] The drug also is believed to slow the rate at which food leaves the stomach.[8]

Before approving a drug for weight loss, the FDA generally requires that such drugs be compared with a placebo in clinical trials that last at least one year and result in clinically meaningful weight loss.[9] After testing several doses of liraglutide for up to one year to assess weight loss effects, the drug’s manufacturer, Novo Nordisk, determined that a much higher dose of up to 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.[10]

In clinical testing, the higher-dose liraglutide did meet the FDA’s effectiveness target. But to keep the weight off, the drug had to be continued. Subjects who stopped taking the drug at the end of the year gained back more than 2 percent of their weight, on average, in just 12 weeks.[11]

'The thought of food makes me want to throw up'

As with previous clinical trials of liraglutide, rates of gastrointestinal side 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.[12] This proved to be a very uncomfortable way to lose weight, and about 6 percent of subjects taking liraglutide withdrew from the weight loss trials due to gastrointestinal adverse events, compared with only 1 percent of placebo-treated subjects.[13]

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:

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.[14]

Dangerous side effects

While many side effects of liraglutide produce only temporary discomfort, a few are more serious. Liraglutide carries a black-box warning because the drug causes thyroid tumors in mice and rats.[15] Severe vomiting can lead to dehydration and kidney impairment.[16] In clinical trials, the drug also quadrupled the rate of pancreatitis, which can be life-threatening.[17]

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.[18] 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.[19] 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.[20]

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 lower than are used in patients with diabetes.[21] 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 stopped taking the drug after they realized they were pregnant.[22]

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 side effects — and even more with the larger-dose weight loss version.

There is currently no medication that can be used safely to achieve weight loss effortlessly and without dangerous side 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.

Just choosing to set a goal for healthy weight loss may be beneficial by itself: One large survey-based study found that people who reported trying to lose weight have lower rates of death, regardless of whether they actually lose weight.[23]

Healthy eating and exercise cannot 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. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm427913.htm. Accessed July 22, 2015.

[2] Ibid.

[3] Public Citizen. Public Citizen to FDA: Pull diabetes drug Victoza from market immediately. April 19, 2012. http://www.citizen.org/pressroom/pressroomredirect.cfm?ID=3586. Accessed July 22, 2015.

[4] Food and Drug Administration. FDA approves new treatment for type 2 diabetes. January 25, 2010. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm198638.htm. Accessed August 13, 2015.

[5] Daily Med. Label: Victoza- liraglutide injection, solution. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5a9ef4ea-c76a-4d34-a604-27c5b505f5a4. Accessed July 22, 2015.

[6] Ibid.

[7] Ibid.

[8] 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. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf. Accessed August 13, 2015.

[9] Food and Drug Administration. Guidance for industry: Developing products for weight management. February 2007. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071612.pdf. Accessed July 22, 2015.

[10] 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. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf. Accessed August 13, 2015.

[11] Ibid.

[12] Ibid.

[13] Ibid.

[14] Ask a Patient. Drug ratings for VICTOZA. http://www.askapatient.com/viewrating.asp?drug=22341&name=VICTOZA&PerPage=60&sort=dateAdded&order=0. Accessed July 22, 2015.

[15] Daily Med. Label: Victoza- liraglutide injection, solution. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5a9ef4ea-c76a-4d34-a604-27c5b505f5a4. Accessed July 22, 2015.

[16] Ibid.

[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. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf. Accessed August 13, 2015.

[18] Ibid.

[19] National Institute of Diabetes and Digestive Kidney Disease. Dieting and gallstones. http://www.niddk.nih.gov/health-information/health-topics/weight-control/dieting_gallstones/Pages/dieting-and-gallstones.aspx. Accessed July 22, 2015.

[20] 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. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf. Accessed August 13, 2015.

[21] Public Citizen. Petition to ban diabetes drug liraglutide. April 19, 2012. http://www.citizen.org/documents/2020.pdf. Accessed August 13, 2015.

[22] 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. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM413317.pdf. Accessed August 13, 2015.

[23] Gregg EW, Gerzoff RB, Thompson TJ, Williamson DF. Intentional weight loss and death in overweight and obese US adults 35 years of age and older. Ann Intern Med. 2003;138:383-389.