A higher-dose version of the diabetes drug liraglutide helped obese people with prediabetes lose three times more weight and slash their odds for progressing to type 2 diabetes by 79% in a new, three-year study. The catch? Volunteers had to give themselves daily injections and must continue indefinitely to maintain the benefits. And the retail price of the drug (without insurance or a discount card) tops $1,000 per month.
Liraglutide (Saxenda) was approved by the FDA for weight loss in late 2014. It’s a glucagon-like peptide-1 (GLP-1) receptor agonist — a newer class of drugs better known for their ability to improve blood-sugar control. The new study, funded by drug maker Novo Nordisk and presented at the Endocrine Society’s 2016 annual meeting in April, tracked 2,254 overweight and obese people who used liraglutide or a placebo for three years while following a weight-loss diet and getting regular exercise. The liraglutide group lost an average of 15 pounds and kept it off, while the placebo group shed about 4 pounds.
“The liraglutide group had an average loss of 6% of their body weight, enough to significantly reduce their risk for progressing from prediabetes to type 2 diabetes,” lead researcher Ken Fujioka, MD, Director of the Center for Weight Management at the Scripps Clinic in La Jolla, CA, told EndocrineWeb.com. “After three years, 66% no longer had prediabetes compared to 33% in the placebo group.”
Volunteers also had high blood pressure and/or, high cholesterol levels at the start of the study. By the end, those in the drug group saw their systolic blood pressure (the top number in a bp reading) decrease nearly 3 points. Their total cholesterol was 2% lower, triglycerides fell 6% and c-reactive protein levels (a measure of body-wide inflammation) fell 29%. The liraglutide group also lost an inch more from their waist lines than the placebo group – a sign that they likely lost more visceral fat, the deep abdominal fat that increases inflammation and contributes to diabetes risk.
“As a weight loss medication, liraglutide is unusual,” Dr. Fujioka says. “It’s a hormone that helps people feel fuller while eating smaller meals. And it keeps people feeling full longer – they can go longer before wanting to eat their next meal. That really helps with sticking with a weight loss plan for the long term.”
The brain is one target of liraglutide’s actions, another new study presented at the same conference suggests. Brain scans of 18 people with type 2 showed that the drug decreased activity in reward centers of the brain when volunteers viewed pictures of tempting food like cake, pastries and fried foods – but not when they looked at images of healthy stuff like fruit and vegetables. “This decreased activation means that individuals on liraglutide find highly desirable foods less attention-grabbing and less rewarding than they typically would without liraglutide,” co-investigator Olivia Farr, PhD, an Instructor in Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in a release from the Endocrine Society. “Thus, this medication may prove to be better for weight loss for people who tend to eat more high-fat food as a reward, such as when they are stressed.”
GLP-1 agonists like liraglutide also improve the body’s ability to process blood sugar in a healthier way by nudging the pancreas to release more insulin and by reducing levels of glucagon, a hormone that increases blood sugar levels.1 While Saxenda is not FDA-approved for diabetes, other GLP-1 agonists are. These include a lower-dose version of liraglutide, Victoza, also made by Novo Nordisk. The daily dose for Saxenda is 3.0 milligrams,2 compared to 1.8 mg for Victoza.3 Other GLP-1 agonists on the market include albiglutide (Tanzeum), dulaglutide (Trulicity) and exenatide (Bydureon, Byetta).
The drugs carry warnings about increased risk for tumors of the thyroid gland, including medullary thyroid carcinoma (MTC; a type of thyroid cancer). “People have a history of medullary thyroid carcinoma or who has inherited multiple endocrine neoplasia type 2 [MEN2, a rare genetic condition that almost always leads to medullary thyroid carcinoma] should not take it,” Dr. Fujioka says. Other warnings listed by the manufacturer for users of Saxenda include the risk of acute pancreatitis, including fatal and non-fatal hemorrhagic; acute gallbladder disease and renal impairment.
Liraglutide comes in a pen for daily injections. Dr. Fujioka says about one in ten people who are candidates for Saxenda shy away from the daily shots. “Most don’t mind,” he says. But Saxenda’s price can be a bigger hurdle. “More and more insurance companies are covering it. But without insurance, the monthly cost can be $1,000 or more,” he says. A prescription savings card from the drug maker can cut the cost to $30 for those whose insurance covers the drug and can reduce the price by $200 for those without coverage.4
Dr. Fujioka, who prescribes the medication to some of his own patients, says the weight-loss version of liraglutide can be a particularly good choice for people with obesity who also have obesity-related health issues. “The patients you want to concentrate on for obesity are those with risk factors such as prediabetes. It’s a pretty big deal that two-thirds no longer had prediabetes in this study. “
1. Fujioka K et al: Liraglutide 3.0 Mg Reduces Body Weight and Improves Cardiometabolic Risk Factors in Adults with Obesity or Overweight and Prediabetes: The Scale Obesity and Prediabetes Randomized, Double-Blind, Placebo-Controlled 3-Year Trial. Presented at ENDO 16, April 2016.
2. Endocrine Society press release: Liraglutide may help nondiabetic overweight and obese adults lose weight and lower risks. Published April 4, 2016. Accessed April 21, 2016. https://www.endocrine.org/news-room/current-press-releases/liraglutide-may-help-nondiabetic-overweight-and-obese-adults-lose-weight-and-lower-risks
2. Endocrine Society: Liraglutide May Make High-Fat Foods Less Desirable to the Brain's Reward Centers. Published April 2, 2016. Accessed April 21, 2016.
1. Koehler et al: Glucagon-Like Peptide-1 Receptor Agonists Increase Pancreatic Mass by Induction of Protein Synthesis. Diabetes 2015;64:1046–1056. http://www.glucagon.com/pdfs/KoehlerDiabetes-2015-1046-56.pdf
2, Saxenda prescribing information. Accessed April 21, 2016. https://www.saxenda.com/
3. MedlinePlus: Liraglutide Injection. Accessed April 21, 2016
6. Saxenda Savings Card. Accessed April 22, 2016. https://www.saxendapro.com/practice-resources/coverage-savings/savings-card.html