Liraglutide (SAXENDA): A Bad Weight-Loss Choice at Any Age

In December 2020, the Food and Drug Administration (FDA) extended the approved treatment population of the chronic weight-management drug SAXENDA — a high-dose formulation of the once-daily injectable drug liraglutide — to include obese children aged 12 and older.[1],[2] The FDA initially approved a lower dose of liraglutide under the brand name VICTOZA in 2010 to treat type 2 diabetes in adults and subsequently approved it to reduce the risk of major cardiovascular events in adults with type 2 diabetes who have a cardiovascular disease.[3],[4]

Like its 2014 approval for obese adults as well as those who are overweight and have at least one weight-related condition (such as high blood pressure, type 2 diabetes or high cholesterol), Saxenda is approved for obese adolescents as an adjunct to lifestyle therapy (reduced-calorie diet and increased physical activity).[5]

Because the evidence supporting Saxenda’s approval in obese adolescents is even weaker than that for obese adults, Public Citizen’s Health Research Group has designated the drug as Do Not Use for all age groups. We also have designated Victoza as a Do Not Use drug for diabetes and unsuccessfully petitioned the FDA in 2012 to ban it because it offers no additional benefits over other diabetes treatments and is associated with increased risks of pancreatitis, thyroid cancer and other serious adverse effects.[6]

Evidence of limited, vanishing benefits from a single trial

Novo Nordisk Inc. (the maker of Saxenda) conducted a single small, randomized, double-blind clinical trial to support use of the drug in obese adolescents who do not have type 1 diabetes.[7] In addition to lifestyle therapy — described as counseling about healthy nutrition and physical activity for weight loss — this trial randomized 251 obese adolescents (average age was 15 years) who had reportedly previously failed to lose sufficient weight with lifestyle modifications into two groups: 125 received Saxenda and 126 received a placebo for 56 weeks (treatment period).

Before starting the treatment period, the subjects’ average body mass index standard deviation scores (the primary endpoint of the trial) were 3.14 and 3.20 in the Saxenda and placebo groups, respectively. At the end of the treatment period, Saxenda subjects had a modest statistically significant beneficial effect (an average 0.23 reduction) on the primary endpoint of the trial, whereas those who received the placebo had no reduction. On average, adolescent subjects taking Saxenda lost 2.7% of their body weight and those who received the placebo gained 2.4% of their body weight.

Importantly, there was no benefit for Saxenda in terms of overall weight-related quality of life or in clinically meaningful indicators, such as cardiometabolic (including cholesterol and fasting insulin levels in the blood) and glycemic tests. Furthermore, the small beneficial effect in the primary endpoint after 56 weeks of treatment with Saxenda disappeared during the 26-week follow-up period after the drug was discontinued — a finding that also occurred in clinical trials evaluating its use in adults. Therefore, the trial investigators acknowledged that “continued treatment” with Saxenda is necessary to maintain its weight-loss benefit. This recommendation is troubling because the trial was too short to support the drug’s long-term use among adolescents, whose organs are still developing.[8] As noted by the European Medicines Agency, it is unclear whether the drug’s effect on weight-related parameters will endure with its long-term use in adolescents.

Poor tolerance, risks and uncertainties

The lone clinical trial evaluating the use of Saxenda in adolescents showed that the drug was poorly tolerated; although it was titrated over up to eight weeks, only 82% reached the full dose of 3 milligrams. In addition, 10% of adolescents taking Saxenda exited the trial before its completion due to the drug’s adverse effects, compared with none in the placebo group.

Gastrointestinal events — including diarrhea, nausea and vomiting — were the adverse effects more frequently reported among adolescents treated with Saxenda (65%) than those who received the placebo (37%). Also, dizziness was reported in 10% of adolescents treated with Saxenda, compared with only 3% of those who received the placebo. Such adverse effects are problematic because they can lower adolescents’ quality of life, which has often already been impaired by obesity. Another potentially concerning trend was that the resting heart rate of Saxenda-treated adolescents increased by three to five beats per minutes in the trial.[9]

Importantly, episodes of hypoglycemia (low blood sugar) occurred among 26 adolescents treated with Saxenda, compared with 18 adolescents taking the placebo in the clinical trial. In addition, one Saxenda-treated adolescent had a moderate episode of pancreatitis (inflammation of the pancreas). Furthermore, small increases in average pancreatic enzyme levels occurred among Saxenda users in this trial, which may be a serious problem with long-term use of the drug, especially when this drug is started in adolescents with a developing pancreas.[10]

An adolescent committed suicide during Saxenda treatment and another two attempted suicide during the follow-up period of the clinical trial, although adolescents with a history of major depressive disorders were excluded. Therefore, Saxenda’s labeling advises that patients taking this drug should be monitored for depression and suicidal thoughts.[11]

What You Can Do

Due to the lack of strong evidence showing long-term, lasting and clinically meaningful benefits of Saxenda that far outweigh its risks, obese adolescents should not take this drug. Likewise, adults should not take this drug or other liraglutide formulations, as discussed in the December 2020 issue of Worst Pills, Best Pills News.[12]

The safest way to lose unwanted pounds for all age groups is to make gradual and consistent lifestyle modifications coupled with behavioral therapy to foster continued motivation and compliance. It is especially important for children to avoid processed foods and sugar-containing foods and drinks and increase their intake of vegetables, fruits and whole grains (such as brown rice) as well as beans and peas, eggs, lean meats, poultry, seafood and soy products.[13] In addition, children need to engage in at least an hour of physical activity per day, which can be achieved through simple, fun activities: jumping rope, playing catch, playing tag, riding a bike, playing basketball or others.

Report all serious adverse events related to Saxenda or other medications to the FDA’s MedWatch adverse-event reporting program by visiting http://www.fda.gov/MedWatch or by calling 800-FDA-1088.
 

References

[1] Novo Nordisk Inc. Label: liraglutide (SAXENDA). June 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206321s015lbl.pdf. Accessed April 6, 2023.

[2] Food and Drug Administration. FDA approves weight management drug for patients aged 12 and older. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-weight-management-drug-patients-aged-12-and-older. December 4, 2020. Accessed April 6, 2023.

[3] Novo Nordisk Inc. Label: liraglutide (VICTOZA). January 2010. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022341lbl.pdf. Accessed April 6, 2023.

[4] Novo Nordisk Inc. Label: liraglutide (VICTOZA). June 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022341s037s038lbl.pdf. Accessed April 6, 2023.

[5] Novo Nordisk Inc. Label: liraglutide (SAXENDA). December 2014. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206321Orig1s000lbl.pdf. Accessed April 6, 2023.

[6] 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 April 6, 2023.

[7] Kelly AS, Auerbach P, Barrientos-Perez M, et al. A randomized, controlled trial of liraglutide for adolescents with obesity. N Engl J Med. 2020;382(22):2117-2128.

[8] European Medicines Agency. Assessment report for liraglutide (Saxenda). Procedure no. EMEA/H/C/003780/ II/0026. April 6, 2021. https://www.ema.europa.eu/en/documents/variation-report/saxenda-h-c-3780-ii-0026-epar-assessment-report-variation_en.pdf. Accessed April 6, 2023.

[9] Novo Nordisk Inc. Label: liraglutide (SAXENDA). June 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206321s015lbl.pdf. Accessed April 6, 2023.

[10] European Medicines Agency. Assessment report for liraglutide (Saxenda). Procedure no. EMEA/H/C/003780/ II/0026. March 25, 2021. https://www.ema.europa.eu/en/documents/variation-report/saxenda-h-c-3780-ii-0026-epar-assessment-report-variation_en.pdf. Accessed April 6, 2023.

[11] Novo Nordisk Inc. Label: liraglutide (SAXENDA). June 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206321s015lbl.pdf. Accessed April 6, 2023.

[12] Liraglutide (SAXENDA): The wrong choice for weight loss. December 2020. Worst Pills, Best Pills News. https://www.worstpills.org/newsletters/view/1372. Accessed April 6, 2023.

[13] National Institute of Diabetes and Digestive and Kidney Diseases. Helping your child who is overweight. June 2021. https://www.niddk.nih.gov/health-information/weight-management/helping-your-child-who-is-overweight. Accessed April 6, 2023.