The latest generation of weight loss drugs seems to have addressed the longstanding American dream of slimming down without suffering. Ozempic (aka, semaglutide) is the most familiar of the class of drugs known as GLP-1 agonists, but there are several other equally effective drugs for those looking to reduce their weight ‘safely’ and predictably. Wegovy has the same chemical constituents as Ozempic, but its dosing is slightly different. Zepbound and Mounjaro (aka, tirzepatide) are known in the trade as a “me-too” drugs, which means that they utilize a slightly different chemical but target the same cell pathways as Ozempic and Wegovy. All of these drugs affect various hormones that manage blood sugar [glucose] levels and stomach emptying. They were developed to help manage adult-onset diabetes mellitus. They showed considerable efficacy in the management of this chronic disease, but it was the weight loss associated with their use that surprised and excited their manufacturers.
Unexpected effects are common occurrences in drug development. Studies are intended to identify problems with drugs but not unintended benefits. Terrible effects can slip through drug development without any evidence of trouble until the drugs are launched and thousands of patients are exposed to what appeared to be a safe and effective drug. In fact, identifying safe and effective drugs is the objective of drug development. That our current methods and safeguards can fail spectacularly was most evident years ago with a drug called thalidomide. This was developed to suppress morning sickness in pregnant women. Animal tests revealed no problems with the drug, and limited studies in women were unremarkable enough to allow for its promotion and wide-spread adoption by many gynecologists and obstetricians. Unfortunately, thalidomide stunted the growth of arms and legs in some fetuses and led to terrible birth defects. It took several years and dozens of deformed babies before a link was established between the drug and the birth defects.
Occasionally investigators stumble upon a benefit from a drug or a natural material, and they simply fail to see what Mother Nature has revealed to them. The classic instance of this was Alexander Fleming’s report on the effects of a common mold, called Penicillin, on bacterial growth. Fleming was studying the effect of saliva (yes, spit) on a variety of germs. After returning from the traditional British summer holiday, he and his colleagues were sorting through culture plates used for growing various bacteria, some of which had been contaminated by molds. He noticed that the Penicillin mold inhibited the growth of some germs. He published this curious observation and went back to his work on saliva. Fortunately, a scientist named Florey saw the potential for a germ-killing agent in the mold that Fleming discarded, and the field of antibiotic development exploded.
Of course, even the most useful drugs may have unwanted effects. Ozempic, Wegovy and their cousins may interfere with normal stomach activity in some people to such an extent that they virtually paralyze the stomach. Alternatively, they occasionally cause serious disturbances in the organ, the pancreas, that makes insulin and glucagon, the hormones most important in blood sugar regulation. What was not evident in the clinical trials involving these [GLP-1 agonist] drugs was their effect on fertility in women. Women who had tried and failed to get pregnant for years got pregnant on the Ozempic-like drugs. Women taking birth control pills to avoid getting pregnant also got pregnant on these medications. Here was an effect so unexpected that drug developers were [and are] at a loss to convincingly explain it.
The fertility effects of these Ozempic-like drugs were a source of joy for some women and a cause of misery for others who discovered they were losing some fat but gaining a fetus. The obvious recommendation was to supplement any birth control pills being used with barrier-type prophylactics, such as condoms or diaphragms, or with IUDs if pregnancy was unwanted. This was a simple solution to an unanticipated problem or benefit, but the boost to fertility raised new concerns, unrelated to its effect on family size or finances. The most likely reason for these unplanned pregnancies was an unidentified effect of these drugs on reproductive or other hormones. What other effects might appear with longterm use could not be anticipated. In fact, what shortterm or longterm effects might be occurring in men taking these GLP-1 agonist drugs remain a mystery.
If GLP-1 drugs can result in pregnancies in women, one must wonder what effects they will have on reproductive organs in men. Additionally, patients must face the possibility of ‘rebound’ weight gain when they stop the medication. Weight loss does not change your body’s insistence on storing fat, just in case there is a famine up the road. Tinkering with the body’s chemistry frequently yields mishaps. What we know for sure is that these GLP-1 drugs are powerful materials that target many more body functions than their developers intended.
Despite the unknowns associated with these drugs, their popularity continues to grow. That you can shed more than a fifth of your body weight over the course of a year with some of these GLP-1 drugs without struggling to diet or exercise is truly remarkable. How long the benefits last remains unknown. Simplifying the dosing of these drugs and expanding access to them is already proceeding rapidly. Ozempic itself is now available as a pill, as well as as an injection. Other Ozempic-like drugs still require injections.
Recommending regular exercise and sensible diets has done little to blunt the obesity epidemic currently confronting Americans. These GLP-1 medications may well be the long-sought treatment for unwonted fat, but they, like most drugs enjoying rave reviews at inception, may prove to be more ‘poison’ than panacea. Remember that heroin was introduced as a ‘safe and effective’ cough suppressant for children, cocaine was believed to be a cure for opium addiction, and frontal lobotomy was widely adopted as the ‘best’ treatment for a variety of psychiatric problems. [By the way, the father of the frontal lobotomy, Antonio Egas Moniz, won a Nobel Prize in 1949 for this medical ‘breakthrough.’] Caveat emptor [buyer beware], as the Romans were fond of saying.
Dr. Lechtenberg is an Easton resident who graduated from Tufts University and Tufts Medical School in Massachusetts and subsequently trained at The Mount Sinai Hospital and Columbia-Presbyterian Medical Center in Manhattan. He worked as a neurologist at several New York Hospitals, including Kings County and The Long Island College Hospital, while maintaining a private practice, teaching at SUNY Downstate Medical School, and publishing 15 books on a variety of medical topics. He worked in drug development in the U.S., as well as in England, Germany, and France.
