DEPRESSION, ALZHEIMER’S, GLP-1’S, COGNITIVE DECLINE

MEDICAL NEWS BRIEFS #28

High fruit and veggie diet decreases risk of depression: It has been reported that women over the age of 45 who eat 4-6, or more, servings of vegetables and fruits per day have a 9%-15% decreased risk of depression compared to women in the lowest intake groups. People who were considered “healthy” (had no major chronic illnesses) had fewer depressive symptoms compared to “unhealthy” patients. These studies were done in Australia and South Africa. The degree of lessening of symptoms was less dramatic in South Africa than in Australia. 

TAKE HOME MESSAGE: A diet high in fruits and vegetables is not only helpful for preventing obesity and cardiovascular disease, it reduces patients’ (especially women) risk for depression.

Reference: Bigelow S, Crosby K, Sachs V, Chong AB, Hobrecht T. High fruit and vegetable intake to Decrease Risk of Depression in Adults. Am Fam Phys 2024 Nov;110(5):533-534.

Evidence Ties Semaglutide (Wegovy, Ozempic, Rybelsus) to Reduced Alzheimer’s Risk: As if there weren’t enough reasons to call GLP-1 receptor agonists “the drugs of the century,’ another very pertinent reason has been reported by Alzheimer’s researchers. “Adults with Type 2 Diabetes who were prescribed …. Semaglutide had a significantly lower risk forAlzheimer’s Disease compared to their peers who were prescribed any of seven other antidiabetic medications, including other types of GLP-1 receptor-targeting medications.” Semaglutide is “neuroprotective in animal models” and is associated with a 40%-70% reduced risk for first-time diagnosis of Alzheimer’s Disease in patients with Type 2 Diabetes. Also reported was evidence “GLP-1’s may protect cognitive function.” Diabetes is a known risk factor for Alzheimer’s Disease so managing diabetes could benefit the brain as well. 

Reference: Brooks M. More Evidence Ties Semaglutide to Reduced Alzheimer’s Disease Risk. Medsacape Medical News 2024 October 24.

Another weight loss drug enters the competition: Experimental drug retatrutide, made by Eli Lilly and Co. has found its way to the head of the “class.” The “class” in this case is GLP-1 receptor agonists, the weight-loss “miracle drugs.” Canadian researchers examined the three commercially available drugs (semaglutide, liraglutide, tirzepatide) and nine drugs (retatrutide, survodutide, mazdutide, orforglipron, beinaglutide, efpeglenatide, exenatide,noiiglutide) yet to be approved. Patients lost the following percentages of weight from baseline:

Approved GLP-1 receptor agonists:

Tirzepatide—15mg once-weekly inj. lost 18% after 72 weeks

Semaglutide—2.4mg once weekly inj. lost 14% after 68 weeks

Liraglutide—3mg once-daily inj. lost 6% after 26 weeks

GLP-1 RA’s yet to be approved:

Retatrutide—12mg once-weekly inj. lost 22% after 48 weeks

Survodutide—lost 6%-15%

Mazdutide—lost 7%-11%

Orforglipron—once-daily oral pill lost 9%-15%

Beinaglutide—0.2mg inj. 3 times a day lost 6%

Efpeglenatide—4-8mg once-weekly inj. lost 7%

Exenatide—10mcg twice-daily inj. lost 5kg (11lbs)

Noiiglutide—once-daily inj. lost 9%

60%-80% of patients had GI side effects (nausea, diarrhea, constipation, vomiting), and 6%—26% had to stop treatment because of side effects. It was also learned that to maintain weight loss, the drugs have to be taken chronically. Retatrutide is not yet FDA approved but should be soon. 

Reference: Ault A. Retatrutide Produces Greatest Weight Loss Medscape Medical News 2025 January 7.

Managing GLP-1Side Effects: Glucagon Like Peptide-1 Receptor Agonists (GLP-1RA’s) are the current rage in weight loss treatment. Despite effective substantial weight loss, they are plagued by gastrointestinal side effects. Nausea, vomiting, constipation, dehydration, gallstones, delayed gastric emptying, and pancreatitis have all been reported. Slow emptying of the stomach makes the patient feel full longer, and one’s appetite is suppressed. Digestion is slowed and that leads to unpleasant side effects. Solutions that prevent GI symptoms suggest the patient start at a low dose and increase the dose slower than the prescribed norm. If side effects occur, reduce the dose or stop increasing the dose until the side effects stop. Frequent small meals are safer than three large meals a day. Fiber, fruits, vegetables help, too. Hydration is important as is avoiding artificial sweeteners. Prescription and OTC drugs reduce symptoms. 

Reference: Novak Sara. Expert tips for Managing GLP-1 Medication Side Effects. Medscape Medical News 2024 December 27. 

A New Weight Loss Drug with No Side Effects? So far, drugs targeting a protein called NK2R show promise. These drugs activate a part of the brain that limits appetite without causing nausea or vomiting. These drugs do not cause loss of muscle mass, bone density, or organ integrity. They are expected to compete with GLP-1’s and be better tolerated.

Reference: Szalinski C. A New Weight Loss Drug with no Side Effects? Yes…so far. Medscape Medical News 2024 December 18. 

Too Much Medication Contributes to Cognitive Decline in the Elderly: Older nursing home residents who had their high blood pressure dosage reduced or stopped had a 12% lower likelihood of cognitive decline compared to patients who remained on the same dose of anti-hypertensive medication. Dementia patients whose BP medication was reduced or stopped had a 16% reduced likelihood of cognitive decline. 

Reference: Chaphalkar A. Cognitive Decline and Antihypertensive Use: New Data. Medscape Medical News 2024 October 15. 

When NOT to prescribe GLP-1RA’s: The GLP-1 receptor agonists (Ozempic, Zepbound, Mounjaro, Wegovy, Rybellsus) are truly reputed to be “miracle drugs,” and have been jokingly referred to as needing to be put in the water. They have already begun to “revolutionize” the treatment of obesity, especially affecting the frequency of bariatric surgery. There are several medical situations, however, where patients should use them with caution or not al all. Those situations are as follows:

   Patients with a family history of medullary thyroid cancer or multiple endocrine neoplasia type 2, both of which are rare diseases. 

   Intestinal motility issues: GLP-1’s slow down the gut delaying emptying of the stomach and slowing intestinal transit times. If one has these conditions already, GLP-1’s make them worse.

   Patients with inflammatory bowel disease (IBD)—Crohn’s disease, Ulcerative Colitis, etc.

   Patients with pancreatitis—GLP-1’s cause it and make it worse.

   Patients with impaired kidney function (eGFR 30 or less). GLP-1’s worsen kidney function.

   Pregnancy—GLP-1’s can cause infant abnormalities—skeletal abnormalities, low birth weight

Widely prescribed and used, GLP-1’s are effective for weight loss.

Reference: Osborne-Roberts TK. GLP-1 RA’s: When Not to prescribe. Medscape Int Med 2024 December 31.