Most people are familiar with the standard methods of weight loss that are accepted and used by millions of folks. I’m talking about Weight Watchers, Jenny Craig, NutriSystem, Optifast, GOLO, the Atkins diet, and on and on. There are dozens, if not hundreds, of diets and programs that claim success, but work only as long as you stay on them. Dieting to lose weight is a reasonable option, but one has to be “patient” as it takes weeks or months to reach your target weight. And although people lose weight while on the diet, they nearly always regain what they lost when they aren’t.
Many patients would, thus, prefer to take a pill to melt away those extra pounds. It’s certainly easier and quicker, yet just as effective. The most commonly used anti-obesity medication ever is phentermine. It’s essentially an amphetamine that was introduced to the market in 1959, but really increased in use after reports in the early 2000’s that when combined with fenfluramine, in Redux, it was more effective the phentermine alone. When doctors were besieged by requests for Redux, they set up weight loss monitoring programs individualized for each patient. Redux was touted as the perfect drug for obese patients wanting to lose weight.
But like so many “perfect” drugs, Redux (fen-phen), was discovered to cause leaky heart valves and pulmonary hypertension (elevated pressure in the arteries carrying blood from the heart to the lungs). These were terrible side effects and patients stopped taking Redux en masse. Redux (Fen-phen) was removed from the market. Phentermine alone did not cause primary pulmonary hypertension, and still is the most often prescribed anti-obesity drug.
That was until recently when subcutaneous injectable glucagon-like peptide-1 (GLP-1) agonists came to market for the treatment of diabetes. Coincidently, GLP-1 agonists not only lower blood sugar and Hgb A1C, they cause weight loss up to 15% or more. The first GLP-1 available was Byetta, developed by Eli Lilly & Co. Early on, Lilly drug reps touted it mainly for better control of diabetes, but also mentioned it caused noticeable weight loss in a population of patients (Type II diabetics) who were obese and needed to lose weight. I stubbornly refused to prescribe Byetta because it was a twice daily injection, and I wasn’t convinced it did all it was reputed to do.
Time has proven me wrong, however! There are now nine GLP-1agonists on the market. Three of them (Ozempic, Rybelsus, Wegovy) are generically semaglutide. This drug is FDA approved and claims to produce a weight loss of 15% or more. Rybelsus is a daily injection; Ozempic and Wegovy are weekly. Similar to semaglutide is liraglutide known commercially as Saxenda, and also FDA approved. It’s a daily injection with a potential 15% weight loss effect. Other weekly injectable GLP-1’s are Trulicity, Bydureon, & Mounjaro, and daily dosing GLP-1’s are Victoza, Bydureon, and twice daily Byetta.
The exact mechanism of action for weight loss with GLP-1’s is unclear, but it is known that they suppress appetite and slow movement of food from the stomach into the small intestine. Thus, the patient feels full sooner and longer and eats less. Since GLP-1’s are drugs for diabetes one might be concerned they cause low blood sugar, but in my research, hypoglycemia was not an oft-mentioned side effect. If one did become hypoglycemic, counter measures are easily done.
Can GLP-1’s be used for weight loss in non-diabetic patients? The answer is “yes,” and the number of prescriptions for this purpose has skyrocketed. GLP-1’s stimulate insulin production and secretion, but only if the blood sugar is elevated. In non-diabetics, hyperglycemia does not occur so the patient is not at risk for hypoglycemia. The combination of delayed gastric emptying, early satiety (satisfaction after eating), and appetite suppression over time leads to significant weight loss.
Phentermine alone is still used for weight loss but with caution and close patient surveillance. It is rapidly being replaced by Glucagon-like Peptide-1 agonists as the most popular and effective treatment for obesity. GLP-1’s are primarily prescribed for diabetics, but are safe to use in obese non-diabetics. Semaglutide is the most effective of these for weight loss, and being a once-weekly injection shouldn’t discourage doctors from prescribing it.
References: Practice Guidelines Medications to Promote Weight Loss: Guidelines from the American Gastroenterological Association Am Fam Phys 2023 October;108(4):424-426.
