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GLP-1 RA’s Role in the Management of Diabetes: Too ...
About GLP-1 RAs
About GLP-1 RAs
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Video Transcription
Hello everyone, I'm Diana Isaacs and I'm going to start off by talking to you about the impact of type 2 diabetes. There are 38.4 million people that have diabetes in the U.S. That is actually 11.6% of the U.S. population. 8.7 million people are undiagnosed. That is about 22.8% of adults with diabetes. 29.7 million people, including 29.4 million adults, are diagnosed. That's 8.9% of the U.S. population. And the percentage of adults with diabetes increases with age, reaching 29.2% among those over the age of 65. Let's talk about why effective management of type 2 diabetes is so critical. The number of cases and the prevalence of diabetes has been steadily increasing over the past few decades and we know that type 2 diabetes can cause serious health complications including atherosclerotic cardiovascular disease, neuropathy, nephropathy, chronic kidney disease, retinopathy, erectile dysfunction, and peripheral artery disease. And the key to prevention of complications is treatment and ongoing management, but there are some barriers to overcome. Next, let's talk about GLP-1 receptor agonists in diabetes management, including the benefits and the efficacy. Clinical trials show the superiority of GLP-1 receptor agonists to other anti-hyperglycemic drugs in improving glycemic efficacy, reducing weight and blood pressure, and having a cardioprotective effect, all without the risk of hypoglycemia when not combined with insulin or sulfonylureas. There can be an increased risk of hypoglycemia when combined with insulin or sulfonylureas, but when this drug class is used on its own, we don't expect it to cause hypoglycemia. GLP-1 receptor agonists lower body weight through their influence on the central nervous system and also slowing gastric emptying. And GLP-1 receptor agonists also reduce cardiovascular events. That includes myocardial infarction, stroke, and associated mortality. And the end goal of diabetes management is to reduce or prevent complications. So there's several additional benefits beyond lowering A1c and weight loss of GLP-1 receptor agonists. That includes lowering blood pressure, improving lipids, improving fatty liver disease, also reducing severity of obstructive sleep apnea, reducing the risk of heart disease and kidney disease, delaying progression of diabetes-related nephropathy, and reducing insulin doses or delaying initiation. Let's talk a little bit more about lowering the risk of hypoglycemia. Hypoglycemia occurs when glucose falls below 70. There is a very low risk of hypoglycemia when a GLP-1 receptor agonist is used alone. However, when taken with other medications that lower glucose, specifically ones that can cause hypoglycemia like sulfonylureas or insulin, that can contribute to hypoglycemia, especially if the doses of the sulfonylurea or insulin are not decreased or stopped. So attention should be given to proactively reducing sulfonylureas or insulin doses when initiating and titrating GLP-1 receptor agonists. There are several GLP-1 receptor agonists that are available, and depending on the type, it may be injected. Most are injected. There is one oral formulation, and some of them are weekly versus others are daily, and we even have one that's twice daily. So dulaglutide is a weekly injection, so it's a xenotide extended release. There is an exenotide immediate release, which is twice daily and needs to be taken 1 to 60 minutes before food. Semaglutide has two formulations. One is a weekly injection, and then the other is actually an oral formulation that is taken every day. Liraglutide and lixisenotide are both daily formulations, although lixisenotide only is available in a combination with insulin-glargine. It is not available by itself. And then we also have terzepatide, which is a dual GLP-1-GIP receptor agonist, and that is also taken once a week. Next, let's talk about potential side effects. So any drug can have some side effects. The most common with GLP-1 receptor agonists are gastrointestinal, and that includes loss of appetite, nausea. If nausea is bad enough, that could lead to vomiting. Diarrhea, although some people actually experience constipation. The GI side effects are typically mild and transient, with the greatest incidents occurring when initiating or with dose escalations. And side effects may be reduced with a slower dose titration. Now there are some other additional potential side effects that can include a mild tachycardia. This is typically an increase in heart rate by like two beats per minute, so not usually clinically significant. There could potentially be an increased risk of infections, indigestion, temporary mild itchiness, or redness at the injection site. Now there are some important safety information to be aware of. Pancreatitis, so generally these drugs have not been studied in people that had a history of pancreatitis. Medullary thyroid cancer, there is a black box warning because when high doses have been given to rodents, they actually developed medullary thyroid carcinomas. So that also, that black box warning also includes anyone that has a personal or family history of medullary endocrineoplasia should not take this medication. And there could be a temporary worsening of diabetes related retinopathy, often with rapid glucose lowering that can worsen pre-existing retinopathy. And there are a few other risks to consider including potential allergic reactions. This is not approved for use during pregnancy. And then hypoglycemia when used along with a drug that could cause hypoglycemia like a sulfonylurea or insulin. Next, let's go ahead and talk about outpatient glucose targets for non-pregnant adults. An A1c level of 6.5% is recommended for most non-pregnant adults as long as it can be achieved safely. To achieve this target level, fasting glucose may need to be less than 110 and the goal for two-hour postprandial glucose is less than 140. But glucose targets should be individualized with consideration for life expectancy, disease duration, presence or absence of micro and macrovascular complications, cardiovascular disease risk factors, comorbid conditions, and risk for hypoglycemia, as well as a person's cognitive and psychological status. So sometimes we may adopt a more less stringent glycemic goal such as an A1c of less than 7% or less than 8% in people with a history of severe hypoglycemia, hypoglycemia unawareness, limited life expectancy, advanced renal disease, extensive comorbid conditions, or long-standing diabetes in which the A1c goal has been difficult to attain despite intensive efforts, so long as the person remains free of hyperglycemia-associated symptoms. When and how should glucose monitoring be used? For starters, we typically want to get an A1c at least every six months in all people with diabetes and at least quarterly in people that are not meeting their glycemic targets. All people that use insulin could be at risk of hypoglycemia and should perform glucose monitoring either through finger sticks with blood glucose monitoring or through continuous glucose monitoring, CGM. For those that are on multiple daily injections of insulin or not meeting their A1c targets or have a history of hypoglycemia, this especially can be done through the use of CGM, which will provide more information than finger sticks. People who do not require insulin or insulin secretagogues may benefit from blood glucose monitoring or from professional CGM, especially to provide feedback about the effects of their lifestyle choices and to assess response to pharmacologic therapy. Professional CGM is typically worn on an intermittent basis, such as two to four times per year compared to personal CGM, which is generally worn all the time. And if a person's not on hypoglycemic medications, blood glucose monitoring or continuous glucose monitoring frequency may be reduced, especially after initiation and titration of GLP-1 receptor agonists. And next, I'd like to go ahead and turn it over to Katie Diamond, who's going to talk about engaging patients.
Video Summary
Diana Isaacs discusses the impact and management of type 2 diabetes, emphasizing the prevalence and undiagnosed cases in the U.S. She highlights the risks of complications such as cardiovascular disease and neuropathy. Effective management, including the use of GLP-1 receptor agonists, is critical. These drugs improve glycemic control, aid weight loss, and reduce cardiovascular events with low hypoglycemia risk when not combined with certain medications. Gastrointestinal side effects and safety considerations, including pancreatitis and thyroid concerns, are noted. Glucose monitoring, individualized treatment goals, and the significance of continual management are emphasized.
Keywords
type 2 diabetes
GLP-1 receptor agonists
continuous glucose monitoring
cardiovascular disease
diabetes management
glycemic control
glucose monitoring
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