The drugs were also noted to reduce food intake and body weight significantly, and some have been approved to treat obesity in the absence of diabetes.
They slow gastric emptying, inhibit the release of glucagon, and stimulate insulin production, therefore reducing hyperglycemia in people with type 2 diabetes.
[2] Another class of anti-diabetes drugs, DPP-4 inhibitors, work by reducing the breakdown of endogenous GLP-1, and are generally considered less potent than GLP-1 agonists.
[8] A 2021 meta-analysis found a 12% reduction in all-cause mortality when GLP-1 analogs are used in the treatment of type 2 diabetes, as well as significant improvements in cardiovascular and renal outcomes.
[12] Likewise, the risk reduction due to SGLT-2 inhibitors was larger in populations with a higher proportion of albuminuria, but this relationship was not observed for GLP-1 receptor agonists.
They are at least as effective as the medications in current use, pioglitazone and Vitamin E, and significantly reduce steatosis, ballooning necrosis, lobular inflammation, and fibrosis according to a 2023 systematic review.
The combination therapy has shown greater efficacy in improving body weight, insulin sensitivity, hyperandrogenism, and menstrual cycle irregularities.
Compared to people using insulin, patients taking GLP-1 agonists showed significant risk reduction in esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancer, as well as meningioma and multiple myeloma.
[15] Patients who take glucagon-like peptide 1 (GLP-1) receptor agonists may be at increased risk of aspiration during anesthesia due to delayed gastric emptying, according to case reports.
[30] As of March 2024, there are 58 personal injury lawsuits for gastroparesis, ileus and intestinal blockage or obstruction in MDL 3094 before Judge Gene E.K.
[33] Additionally, while adolescents taking GLP-1 drugs experienced more gastrointestinal symptoms, they had a lower risk of acute pancreatitis compared to the control group.
[35] A large study published in Nature Medicine suggested that GLP-1 agonists may result in hypotension (low blood pressure), syncope (fainting), arthritic disorders, nephrolithiasis (kidney stones), interstitial nephritis, and drug-induced pancreatitis.
[39] In the United States, cost is the highest barrier to GLP-1 agonist usage and was reported as the reason for discontinuation in 48.6% of U.S. patients who stopped using the drugs.
[48][28] Combination with glucagon agonism is likely to make the drugs more efficacious for weight loss, at the expense of additional risk and a lower therapeutic index.
[29][49] The experimental formula cagrilintide/semaglutide combines semaglutide with a dual amylin and calcitonin receptor agonist for additional weight loss.
This is illegal in the U.S., but some buyers turn to unauthorized retailers after being denied insurance coverage and being unable to afford the name-brand drug.
[57] In the United States, the FDA declared shortages of injectable versions of semaglutide, tirzepatide, dulaglutide, liraglutide, and exenatide in 2022.
[58] During a declared shortage, compounding pharmacies are allowed to sell custom-made versions of the drug if they obtain the active pharmaceutical ingredient from an FDA-approved facility.
[62][63][64] In 2002, Eli Lilly entered into an alliance with Amylin to further develop exenatide and secure official approval to market the drug.
[63][64] Thirty years later, the pharmaceutical industry had come full circle from the mid-1990s, when Eng was attending one conference after another to present his poster about exendin-4 and was repeatedly met with a lack of interest.
[64] The June 2024 conference of the American Diabetes Association in Orlando, Florida, included presentations on at least 27 GLP-1 receptor agonists then in development.
[67] By July 2024, Novo Nordisk's semaglutide and Eli Lilly's tirzepatide were ranked among the most popular and lucrative drugs in the world.