In the last ten years, almost 200 million new cases of diabetes mellitus have been officially registered, and this number is only increasing with our current lifestyle and diet. Diabetes mellitus is a chronic metabolic disorder characterized by high blood sugar levels over a prolonged period. It results from defects in insulin secretion, insulin action, or both. There are two main types of diabetes mellitus:
Type 1 Diabetes Mellitus: An autoimmune disease where the body's immune system attacks and destroys the insulin-producing beta cells in the pancreas. This type typically develops in children and young adults, and patients require lifelong insulin therapy for survival.
Type 2 Diabetes Mellitus: A condition in which the body becomes resistant to the effects of insulin or the pancreas fails to produce enough insulin. This form of diabetes is more common in adults, especially those who are overweight or obese, and is strongly associated with lifestyle factors such as poor diet, physical inactivity, and genetic predisposition.
Diabetes mellitus is a significant public health concern due to its association with severe complications that can lead to reduced quality of life and increased mortality. These complications include:
Cardiovascular Disease: People with diabetes are at higher risk of heart disease and stroke.
Neuropathy: Nerve damage that can lead to pain, tingling, and loss of sensation, particularly in the extremities
Nephropathy: Kidney damage that can result in chronic kidney disease or kidney failure.
Retinopathy: Eye damage that can lead to blindness.
Foot Problems: Poor blood flow and neuropathy in the feet increase the risk of infections and amputations.
Effective management of diabetes mellitus involves lifestyle modifications such as a balanced diet, regular physical activity, and weight management. In addition to lifestyle changes, pharmacotherapy plays a crucial role in controlling blood glucose levels and preventing complications.
Treatment for Diabetes Mellitus:
Type 1 Diabetes: The primary treatment is insulin therapy, which can be delivered through injections or an insulin pump. Regular monitoring of blood glucose levels is essential.
Type 2 Diabetes: Treatment often starts with oral medications such as metformin, sulfonylureas, DPP-4 inhibitors, and thiazolidinediones. Injectable options, including GLP-1 receptor agonists and insulin, may be added if oral medications are insufficient to control blood glucose levels.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are medications used to treat type 2 diabetes mellitus by mimicking the incretin hormone GLP-1. They enhance insulin secretion, inhibit glucagon release, delay gastric emptying, and reduce appetite, resulting in improved glycemic control and weight loss. Common GLP-1 RAs include exenatide, liraglutide, dulaglutide, semaglutide, and lixisenatide. These medications effectively lower HbA1c levels and have shown cardiovascular benefits, particularly in patients with established heart disease. Side effects may include gastrointestinal issues, risk of pancreatitis, and injection-site reactions. GLP-1 RAs are contraindicated in patients with a history of medullary thyroid carcinoma or pancreatitis.
Recent findings indicate that the use of GLP-1 receptor agonists for managing type 2 diabetes has increased significantly due to the weight loss experienced as a side effect. The FDA has approved the use of Wegovy for weight loss, but many people use GLP-1 receptor agonists like Ozempic off-label for this purpose. This has led to a worldwide shortage of the drug for type 2 diabetes patients.
A recent study published in the Annals of Internal Medicine showed that there were more than 1 million new GLP-1 receptor agonist users between 2011 and 2023, many of whom did not have diabetes mellitus but had a body mass index (BMI) of 30 kilograms per square meter (kg/m²) or greater. The study also found that the use of non-FDA-approved GLP-1 drugs increased from 0.21% in 2019 to 0.37% in 2023.
The study was population-based and involved the medical records of 45 million patients from the United States listed in TriNetX, a real-time federated health research network. It included patients who had at least one outpatient or inpatient doctor visit between 2011 and 2023. Scientists studied various factors, including BMI and demographics, and concluded that there are over 1 million GLP-1 RA users. The study also found that most GLP-1 users were white, non-Hispanic females.
Dr. David Cutler, a board-certified family medicine physician at Providence Saint John's Health Center, raised concerns about how health insurance coverage affects the availability of these medications. He explained that even if doctors prescribe these medications, patients may not obtain them if they are not covered by insurance, worsening the situation. He emphasized that insurance companies need to reevaluate their policies and establish criteria to obtain this medication.
There is also variability in how they cover the drugs when used for diabetes. Regardless of which drug or which disease, access to the drug may be limited to some patients due to cost. This inevitably leads to racial, ethnic, and other socioeconomic disparities in access. Since control of diabetes and obesity are significant health outcome risk factors, it is conceivable that the shortages and high cost of GLP1 agonists will exacerbate existing health disparities
Dr. David Cutler MD
GLP-1 RAs are expensive drugs with high demand among diabetic patients due to their efficacy. However, their use as weight loss drugs has led to a shortage. FDA-approved companies are profiting without real competition, even though there are non-FDA-approved drugs available. Buyers should be cautious when purchasing non-approved drugs.
Fixing this issue is complicated due to factors like pharmaceutical licensure, manufacturing, and distribution. FDA-approved companies excel in these areas, so changes in insurance policies and increased production by these companies are necessary. Although non-approved companies are selling the drug at lower prices, they are still not FDA-approved.
This is a trend we’ve been seeing and it’s been seen by other studies as well that there’s a shortage of these medications because it’s a much broader indication now than just diabetics — it’s patients who are obese and don’t have diabetes can get these medications. The typical hurdles our patients are facing is first, getting covered by insurance, which is another separate issue because if there were more people covered, there’d be an even greater shortage of these medications
Dr. Mri Ali MD
Research is ongoing regarding the use of GLP-1 RAs for metabolic-associated steatohepatitis, which could further impact availability but holds great future significance. More research on the safety of non-FDA-approved GLP-1 drugs at lower prices could potentially help resolve this issue.
Conclusion:
The rising incidence of diabetes mellitus, particularly type 2 diabetes, highlights the urgent need for effective management strategies. GLP-1 receptor agonists have proven to be a valuable treatment option, offering significant benefits in glycemic control and weight management. However, the increased off-label use of these drugs for weight loss has led to shortages, impacting patients who rely on them for diabetes management. Addressing this issue requires a multifaceted approach involving policy changes, increased production, and careful consideration of insurance coverage. Ensuring that GLP-1 RAs remain accessible and affordable for those who need them most is crucial for improving public health outcomes in the fight against diabetes.
Reference :
1. Pelc, C. (2024, July 25). Who uses GLP-1 drugs, and for what? Is it worsening diabetes drug shortages?https://www.medicalnewstoday.com/articles/glp-1-drugs-diabetes-drug-shortages#Twofold-increase-in-GLP-1-drug-users-without-diabetes
2. Diabetes. (2023, April 5). https://www.who.int/news-room/fact-sheets/detail/diabetes
3. GLP-1 agonists: Diabetes drugs and weight loss. (2022, June 29). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/expert-answers/byetta/faq-20057955
4. Collins, L., & Costello, R. A. (2024b, February 29). Glucagon-Like Peptide-1 Receptor Agonists. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK551568/#:~:text=Glucagon%2Dlike%20peptide%2D1%20(,options%20for%20these%20endocrine%20diseases.
By Yash Kamble
