Liraglutide

Natural GLP-1 lasts only a minute or two before enzymes such as DPP-4 break it down. Liraglutide shares 97% of its amino-acid sequence with human GLP-1 but carries a fatty-acid chain; it binds blood proteins, clumps together under the skin, and resists those enzymes, giving it a half-life of about 13 hours^1,2. It activates GLP-1 receptors on pancreatic beta cells, raising insulin release when glucose is high, and lowers glucagon in the same glucose-dependent way; it also slows stomach emptying¹. GLP-1 receptors sit in brain areas that regulate appetite, and in animal studies liraglutide reached such regions, including the hypothalamus, and activated neurons there. Per its label, the weight loss comes from lower calorie intake, not from higher energy expenditure².

Two large human trials anchor its evidence. LEADER randomized 9,340 people with type 2 diabetes and high cardiovascular risk to liraglutide or placebo for a median 3.8 years. Cardiovascular death, nonfatal heart attack or nonfatal stroke occurred in 13.0% versus 14.9% (hazard ratio 0.87), and both cardiovascular and all-cause deaths were lower³. The SCALE Obesity and Prediabetes trial enrolled 3,731 adults with obesity, or overweight plus high blood pressure or abnormal lipids, and no diabetes. Over 56 weeks, alongside lifestyle counseling, mean weight fell 8.4 kg on liraglutide versus 2.8 kg on placebo; 63% versus 27% lost at least 5% of body weight. Nausea and diarrhea were the most frequent complaints, and serious adverse events occurred in 6.2% versus 5.0%⁴.

The FDA approved liraglutide in 2010 as Victoza for type 2 diabetes (now including children 10 and older) and to reduce major cardiovascular events in adults with diabetes and heart disease, and in 2014 as Saxenda for chronic weight management in adults and adolescents 12 and older^1,2. Generic liraglutide and a combination with insulin degludec (Xultophy) are also FDA-approved.

Per FDA labels, the most common effects are digestive: nausea, diarrhea, vomiting, constipation, indigestion and reduced appetite, plus headache, injection-site reactions and, with insulin or sulfonylureas, low blood sugar. A boxed warning describes thyroid C-cell tumors in rodents; it is contraindicated with a personal or family history of medullary thyroid cancer or MEN 2. Other warnings: pancreatitis, gallbladder disease, severe digestive reactions, kidney injury from dehydration, raised heart rate, serious allergic reactions and aspiration during anesthesia^1,2.

1. FDA label: VictozaFDA label (DailyMed)
2. FDA label: SaxendaFDA label (DailyMed)
3. Marso et al., N Engl J Med 2016PubMed
4. Pi-Sunyer et al., N Engl J Med 2015PubMed