New weight loss and dementia medications: Understanding the benefits and risks

New medications developed over the course of the past few years to treat Alzheimer’s disease and aid in weight loss have garnered a great deal of attention through the media and advertising. That attention has led more people to ask their physicians to prescribe these medications. What’s sometimes lost in the excitement surrounding new treatments is a clear understanding of the benefits and risks of these medications and which patients are appropriate candidates for new treatments.

All medications, both new and older, come with potential side effects and the possibility of an adverse reaction. When a medication goes through the clinical trial process and receives FDA approval, those risks are noted and weighed against the potential benefit the medication offers.

Any time your physician prescribes a medication, or you inquire about getting a prescription for a new medication, it’s important to discuss both the benefits and risks. Your PinnacleCare Health Advisor can help you make an informed decision by providing in-depth, evidence-based information on the medication.

What to know about new weight loss medications

Originally developed and FDA approved to treat type 2 diabetes, several of these medications have recently been approved for weight loss, while others are prescribed off label (to treat a condition other than the one the medication was FDA approved to treat). In addition to an injectable form, some of the medications have recently been released in a pill formulation.

The most effective class of medications is the GLP-1 receptor agonists (GLP-1 RAs). GLP-1 is a hormone made by the small intestine. It plays several roles, including:

• Triggering the release of insulin from the pancreas
• Blocking the release of the hormone glucagon, which helps raise blood sugar levels when needed
• Slowing the emptying of the stomach, which decreases the amount of glucose from food that enters the bloodstream
• Increasing satiety or a feeling of fullness after eating

GLP-1 RAs bind to GLP receptors and trigger the effects that the naturally occurring hormone would, lowering blood sugar and supporting weight loss. There are several medications in this class, including the injectable semaglutides Ozempic and Wegovy and the oral semaglutide Rybelsus and the injectable tirzepatides Zepbound and Mounjaro, which are both GLP-1 RAs and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists.

The health benefits of GLP-1 RAs

A number of studies have found that these medications, in combination with a change in diet and exercise, led to significant weight loss. One study that included 1,961 obese adults compared the outcomes of those using semaglutide plus lifestyle changes with people who only made lifestyle changes. After 68 weeks, half of the trial participants using the medication had lost 15% of their bodyweight and almost a third had lost 20%. The trial participants who only made lifestyle changes lost approximately 2.4% of their bodyweight over the course of the study.

For people who were also living with diabetes, these medications helped significantly lower A1C. People taking .5 mg per week experienced decreases of .32 to .79 percentage points, while the A1C of those taking 1 mg per week decreased 0.38 to 1.07 percentage points.

The recent SELECT trial also found that semaglutide had a positive impact on heart health. At a dose of 2.4 mg per week, the medication was associated with a 20% reduction in major cardiovascular events compared to placebo. Another double-blind, placebo controlled trial, STEP-HFpEF, found that the same dose was associated with improved symptoms and physical function for people with heart failure with preserved systolic function and obesity.

The FLOW trial uncovered an association between 1 mg weekly of semaglutide and a reduction in the progression of kidney disease. The patients in the trial received either the standard of care treatment or the standard of care treatment plus semaglutide. Participants in the second group experienced a 24% reduction in disease progression and cardiovascular and kidney disease related death.

The potential side effects and risks of new weight loss medications

The most common side effects and potential health risks associated with GLP-1 RAs include:

• Gastrointestinal side effects such as nausea, vomiting, diarrhea, and constipation
• Gastroparesis, a rare, but serious, dysfunction of the nerves and muscles of the stomach that leads to stomach paralysis and an inability of the stomach to empty
• Diabetic retinopathy complications uncovered in a two-year trial involving patients with type 2 diabetes and high cardiovascular risk. More events of diabetic retinopathy complications occurred in patients treated with Ozempic® (3.0%) compared with placebo (1.8%).
• Acute and chronic pancreatitis
• Acute kidney injury and worsening of chronic renal failure, although the FLOW study found the opposite result
• Risk of thyroid C-cell tumors, although a recent large study found no significant increase in thyroid cancer risk

For most people, side effects resolve during the first few weeks after starting treatment. Because of the possibility of more serious side effects, it’s important to ask your physician what symptoms may be signs of a serious side effect and to see your physician if you experience any of these symptoms. You should also see your physician for regularly scheduled appointments to check your progress with the medication and screen for any issues.

New medications to treat Alzheimer’s disease

Dementia caused by Alzheimer’s disease involves damage to the brain from abnormal clumps of proteins called amyloid plaques and tangled bundles of fibers called neurofibrillary, or tau, tangles. While no currently available medications can reverse the progression of Alzheimer’s disease, new monoclonal antibody medications that target the disease process and slow the disease’s progression are now available.

One of the first medications on the market, sold under the brand name Aduhelm, never showed clinical benefit and is being discontinued so the manufacturer can focus its resources on a newer medication, lecanemab (Leqembi), and the development of new treatments.

Lecanemab was approved by the FDA last year for people with early-stage Alzheimer’s disease after it showed moderate slowing of the decline in cognition and function in a clinical trial. The medication works by targeting the amyloid plaques and tau tangles that build up in the brains of people with this type of dementia and disrupt brain function. In a trial involving 1,795 participants with early-stage, symptomatic Alzheimer’s disease, lecanemab slowed clinical decline by 27% after 18 months of treatment compared with those who received a placebo.

Study participants had a significant reduction in amyloid burden in imaging tests and usually reached normal levels by the end of the trial. Participants also showed a 26% slowing of decline in a key secondary measure of cognitive function and a 37% slowing of decline in a measure of daily living compared to the placebo group.

A second medication, donanemab, is still under review by the FDA. The TRAILBLAZER-ALZ2 trial found that the drug significantly slowed cognitive and functional decline in people with early, symptomatic Alzheimer’s disease.

In the trial, 47% of participants taking the medication showed no decline on Clinical Dementia Rating-Sum of Boxes, a key measure of disease severity, at one year, compared to 29% of participants on placebo. Trial participants receiving the medication also had a 40% less decline in ability to perform activities of daily living and a 39% lower risk of progressing to the next stage of disease compared to placebo.

What are the risks of new Alzheimer’s medications?

Like all medications, both of these new treatments have potential side effects and risks. Common side effects include infusion-related reactions, such as fever, chills, body aches, headache, nausea, vomiting, dizziness, changes in heart rate, and shortness of breath.

The medications also have the potential to cause more serious side effects, including brain swelling and small bleeds in the brain. In most cases, these effects do not cause symptoms or serious health effects. However, in rare cases, brain swelling and bleeding has the potential to cause health issues, including:

• Headache
• Confusion
• Dizziness
• Vision changes
• Nausea
• Difficulty walking
• Seizures
• Larger brain bleeds, which can cause death

Some people are not candidates for these medications due to other health factors that increase the risk of serious adverse effects. These include people:

• With two copies of the APOE e4 gene, which increases the risk of brain swelling or bleeding
• On blood thinners
• Who’ve had a stroke, transient ischemic attack, or heart attack within the year
• Who have a history of brain cancer
• With a history of alcohol or substance use disorder within the past two years
• Who take other monoclonal antibody medications

Get the support of PinnacleCare

Any time your physician prescribes a medication, or you inquire about getting a prescription for a new medication, it’s important to discuss both the benefits and risks. Your PinnacleCare Health Advisor can help you make an informed decision by providing in-depth, evidence-based information on the medication. Connect with our team to learn more.