FDA NewsPerspective

FDA approves Saxenda injection therapy for weight management

The FDA granted approval to liraglutide 3-mg injection as the first once-daily human glucagon-like peptide-1 analogue to help manage obese or overweight patients, according to a press release from the agency.

Liraglutide 3-mg injection (Saxenda rDNA origin, Novo Nordisk) is approved for adults with obesity with BMI ≥30 kg/m2 or overweight adults with BMI ≥27 mg/m2 and at least one weight-related comorbidity including hypertension, type 2 diabetes or high cholesterol dyslipidemia to use along with diet and physical activity, according to the press release.

“Saxenda, used responsibly in combination with a healthy lifestyle that includes a reduced-calorie diet and exercise, provides an additional treatment option for chronic weight management for people who are obese or are overweight and have at least one weight-related comorbid condition,” James Smith, MD, MS, acting deputy director, Division of Metabolism and Endocrinology Products, FDA Center for Drug Evaluation and Research, said in the press release.

The therapy should not be used in combination with other drugs belonging to this class of glucagon-like peptide-1 (GLP-1) receptor agonists, including liraglutide recombinant 18 mg (Victoza, Novo Nordisk) designed to treat type 2 diabetes, according to the statement.

The safety and efficacy of liraglutide 3 mg were evaluated in three clinical trials involving approximately 4,800 patients with obesity and overweight; the patients, both with and without significant weight-related conditions, also received counseling on lifestyle modifications for reduced-calorie diet and regular physical activity.

In a clinical trial that enrolled patients without diabetes, average weight loss from baseline was 4.5% with treatment vs. placebo at 1 year; 62% of patients treated with liraglutide lost ≥5% of their body weight compared with 34% of patients treated with placebo.

In another clinical trial that enrolled patients with type 2 diabetes, average weight loss from baseline was 3.7% with treatment vs. placebo over the same period; 49% of patients treated with liraglutide lost ≥5% of their body weight compared with 16% of patients treated with placebo.

Patients receiving liraglutide 3 mg should be evaluated after 16 weeks, according to the release, if <4% of baseline body weight is not lost, the patient is unlikely to achieve and sustain clinically meaningful weight loss and therapy should be discontinued.

A boxed warning indicates thyroid gland tumors have been observed in rodent studies, but it remains unknown whether it has the same effect in humans. The drug is contraindicated for patients with personal/family history of medullary thyroid carcinoma (MTC) or those with multiple endocrine neoplasia syndrome type 2, according to the statement.

The most common side effects observed in patients during clinical trials were nausea, diarrhea, constipation, vomiting, hypoglycemia and decreased appetite. Other reported side effects include pancreatitis, gallbladder disease, renal impairment and suicidal thoughts. The drug can raise heart rate and should be discontinued if increased resting heart rate continues.

Post-marketing studies required by the FDA include: trials for dosing, safety and efficacy in pediatric patients; a case registry of ≥15 years to identify any treatment-related increase in medullary thyroid carcinoma; and ongoing trials to evaluate potential breast cancer risk.

“Obesity has many root causes and there is a clear need for additional treatment options to help health care professionals better address our patients' individual conditions and goals for weight management,” Donna Ryan, MD, professor and associate director of clinical research at the Pennington Biomedical Research Center, said in a press release. “The approval of Saxenda provides us with a new therapeutic approach for helping our patients achieve and maintain a healthier body weight.”

The FDA granted approval to liraglutide 3-mg injection as the first once-daily human glucagon-like peptide-1 analogue to help manage obese or overweight patients, according to a press release from the agency.

Liraglutide 3-mg injection (Saxenda rDNA origin, Novo Nordisk) is approved for adults with obesity with BMI ≥30 kg/m2 or overweight adults with BMI ≥27 mg/m2 and at least one weight-related comorbidity including hypertension, type 2 diabetes or high cholesterol dyslipidemia to use along with diet and physical activity, according to the press release.

“Saxenda, used responsibly in combination with a healthy lifestyle that includes a reduced-calorie diet and exercise, provides an additional treatment option for chronic weight management for people who are obese or are overweight and have at least one weight-related comorbid condition,” James Smith, MD, MS, acting deputy director, Division of Metabolism and Endocrinology Products, FDA Center for Drug Evaluation and Research, said in the press release.

The therapy should not be used in combination with other drugs belonging to this class of glucagon-like peptide-1 (GLP-1) receptor agonists, including liraglutide recombinant 18 mg (Victoza, Novo Nordisk) designed to treat type 2 diabetes, according to the statement.

The safety and efficacy of liraglutide 3 mg were evaluated in three clinical trials involving approximately 4,800 patients with obesity and overweight; the patients, both with and without significant weight-related conditions, also received counseling on lifestyle modifications for reduced-calorie diet and regular physical activity.

In a clinical trial that enrolled patients without diabetes, average weight loss from baseline was 4.5% with treatment vs. placebo at 1 year; 62% of patients treated with liraglutide lost ≥5% of their body weight compared with 34% of patients treated with placebo.

In another clinical trial that enrolled patients with type 2 diabetes, average weight loss from baseline was 3.7% with treatment vs. placebo over the same period; 49% of patients treated with liraglutide lost ≥5% of their body weight compared with 16% of patients treated with placebo.

Patients receiving liraglutide 3 mg should be evaluated after 16 weeks, according to the release, if <4% of baseline body weight is not lost, the patient is unlikely to achieve and sustain clinically meaningful weight loss and therapy should be discontinued.

A boxed warning indicates thyroid gland tumors have been observed in rodent studies, but it remains unknown whether it has the same effect in humans. The drug is contraindicated for patients with personal/family history of medullary thyroid carcinoma (MTC) or those with multiple endocrine neoplasia syndrome type 2, according to the statement.

The most common side effects observed in patients during clinical trials were nausea, diarrhea, constipation, vomiting, hypoglycemia and decreased appetite. Other reported side effects include pancreatitis, gallbladder disease, renal impairment and suicidal thoughts. The drug can raise heart rate and should be discontinued if increased resting heart rate continues.

Post-marketing studies required by the FDA include: trials for dosing, safety and efficacy in pediatric patients; a case registry of ≥15 years to identify any treatment-related increase in medullary thyroid carcinoma; and ongoing trials to evaluate potential breast cancer risk.

“Obesity has many root causes and there is a clear need for additional treatment options to help health care professionals better address our patients' individual conditions and goals for weight management,” Donna Ryan, MD, professor and associate director of clinical research at the Pennington Biomedical Research Center, said in a press release. “The approval of Saxenda provides us with a new therapeutic approach for helping our patients achieve and maintain a healthier body weight.”

    Perspective
    John Morton

    John Morton

    The recent approval of Saxenda indicates that both science and the marketplace are moving toward more solutions for obesity, and that there is a real recognition that obesity is a disease just as the American Medical Association recognized.

    Multiple options are required when treating a disease. We will likely begin to see a more integrated treatment approach for patients with obesity, similar to those for heart disease and cancer, with complementary interventions.

    The mechanism by which Saxenda works is interesting because it is really founded on the principles learned from bariatric surgery. We know that very high diabetes remission rates are seen, particularly with gastric bypass, and this is based in part on the GLP-1 agonist effect.

    Drug developers have reverse-engineered what we have seen in bariatric surgery practice. Based on the data for Saxenda, it is not going to be for everyone, but it is an option for some patients. Even a modest amount of weight loss, as seen in the study, is beneficial.

    It is also interesting to consider how the drug may work in bariatric surgery patients, before or after surgery. Theoretically, there could be some priming-of-the-pump with the use of this drug, augmenting the effect of the surgery to some degree because they both work on up-regulation of GLP-1.

    Saxenda could be helpful for patients who are thinking about surgery but need to lose some weight ahead of time, and potentially be a salvage therapy for patients who, on the rare occasion, regain some weight.

    • John Morton, MD, MPH, FACS
    • Chief, Bariatric and Minimally Invasive Surgery, Stanford University School of Medicine President, American Society for Metabolic and Bariatric Surgeons

    Disclosures: Morton reports no relevant disclosures.