Obesity and Diabetes — 10

Almost forty million Americans have sleep apnea. The favorable impact of GLP-1 drugs for treating sleep apnea in people with obesity was documented in two randomized trials of tirzepatide. Along with the marked weight loss, there was substantial reduction of apnea (nearly 60%), oxygen desaturation in the blood, patient-reported sleep impairment and disturbance, systolic blood pressure, and the inflammation marker C-reactive protein. Notably, all these improvements occurred in patients using or not using continuous positive airway pressure (CPAP) machines. The results have put in question the relative need for CPAP in the future, a device that many patients love to hate, or refuse to use.

What about GLP-1 drugs affecting cancer? While there are no randomized trials to draw from, in a study of 1.6 million people with type 2 diabetes, among those treated with GLP-1 drugs compared with insulin, there was reduction in eleven of thirteen cancers that are associated with obesity. Separately, from a study of 1.2 million people with type 2 diabetes, there was a marked reduction of colorectal cancer in those taking GLP-1 drugs compared with either insulin or metformin, even in those who were not overweight or obese. It’s harder to attribute these findings to weight loss, which is much less pronounced among diabetics. Perhaps it is a result of the direct anti-inflammatory effect or the known activation of T cells with antitumor activity in preclinical models.

Several reports suggest that GLP-1 drugs have other diverse benefits, such as a 50 percent reduction in alcohol intake; enhancement of fertility in women with polycystic ovary syndrome (“Ozempic babies”); reduction or cessation of tobacco abuse, gambling, and nail-biting; and treatment of autoimmune disorders such as psoriasis, arthritis, and asthma as well as depression. You’ll note that many of these conditions have little to do with obesity or weight loss. And yes, antiaging properties have also been identified. Simply put, it’s hard to find a possible indication that hasn’t been raised for GLP-1 drugs.

The news about GLP-1 drugs is not all good. In the trial with the longest follow-up at high doses (to almost forty months), twice as many people permanently discontinued the drug (16.6%) compared with placebo (8.2%). The main reason was the fivefold increase in gastrointestinal disorders that include nausea, diarrhea, vomiting, constipation, and abdominal distension, which typically occur early after treatment initiation, and rare cases of acute pancreatitis, acute gall bladder disease, and gastroparesis (slowing or cessation of food moving from stomach to intestine). Resting heart rates increase on the drugs; though usually only by a few beats per minute, in some people this can be substantial, up to twenty beats per minute. Blurred vision and exacerbation of diabetic retinopathy are known risks, even though the latter would be expected to be reduced over the longer term with better glucose control. More serious is one report of a higher incidence of a type of optic neuropathy (nonarteritic anterior ischemic optic neuropathy, which can result in sudden vison loss, frequently called an “eye stroke”) in an observational study of people taking semaglutide compared with matched controls. But other studies have found just the opposite, so this risk remains uncertain. It also goes against the anti-inflammatory properties of GLP-1 drugs, but time will tell if it is a risk rather than a spurious association. Anesthesiologists have raised the concern that patients undergoing surgery should not take their GLP-1 medication for seven days prior to reduce the problem with vomiting and aspiration pneumonia, but this is not resolved. The drugs are contraindicated in people with rare forms of cancer: medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.