There is no end to the information reported by clinicians on the benefits and effects of glucagon-like peptide-1 receptor agonists (GLP-1). It seems a new reason to prescribe the drugs emerges every week while adverse events pile up the more the drugs are used. The two examples of this drug class that stand out are tirzepatide (Zepbound, Mounjaro) and semaglutide (Ozempic, Rybelsus, Wegovy).
Zepbound and Mounjaro are both products made by Eli Lilly & Co. They both contain tirzepatide and do the same thing. So, why does Eli Lilly have two brands of the same drug? Well, it’s because the FDA did not, or would not, approve either drug for both Type 2 Diabetes and weight loss! Therefore, Mounjaro is approved for lowering blood sugar in patients with Type 2 Diabetes, and Zepbound is approved for weight loss. They are the exact same drug, with two brand names that have different indications for use.
To lower blood sugar, Mounjaro causes an increase in the release of insulin in response to a high blood sugar. To cause weight loss Zepbound slows transition time of food through the intestinal tract, delays gastric emptying, and effectively suppresses one’s appetite.
Ozempic, Wegovy, and Rybelsus are all made by Novo Nordisk. All three contain semaglutide and do the same thing. Like Eli Lilly, Novo Nordisk has 3 brands of the same drug, two-of-which are indicated for treating Type 2 Diabetes (Ozempic, Rybelsus) and Wegovy is indicated for weight loss. Ozempic and Rybelsus both cause the release of insulin in response to a high blood sugar. The difference between them is Ozempic is a once-weekly injection and Rybelsus is a once-daily oral tablet.
Since we have five brands of the two most effective GLP-1 receptor agonists, tirzepatide and semaglutide, it now comes down to finding out which one is more effective and lowering blood sugar, which is more effective at causing weight loss, and which one has fewer adverse effects. While I haven’t seen any information that says one is more effective at lowering blood sugar, I have seen studies comparing the amount of weight loss.
Tirzepatide prescribed for overweight or obese people, was “significantly more likely to achieve weight loss than semaglutide at 3 months, 6 months, and 12 months. In a 36-week period, tirzepatide resulted in a 20.9% weight loss, and from 36-88 weeks, patients lost an additional 5.5%. Individuals who were not diabetic had larger weight reductions than those with Type 2 Diabetes. During the same study period, patients on placebo gained 14% more weight. At the end of the 88-week period, nearly 90% of participants had stayed at a weight that was at least 80% of what they had lost.
The conclusion reached by Rodriguez et al. was “tirzepatide was associated with significantly greater weight loss than semaglutide.” That gives tirzepatide a true advantage!
Along with the good must come the bad, or at least the adverse. No drug is perfect (except for maybe statins) so the use of GLP-1 receptor agonists can be fraught with problems and adverse reactions. I previously reported on the increased chance for GI side effects, and most alarmingly the development of acute pancreatitis, a potentially serious problem. Now, also come reports of a concern for vision loss.
Type 2 Diabetes, in addition to being characterized by insulin resistance, obesity, and high blood sugar, also is a generalized inflammatory vasculitis. That means that a diabetic’s blood vessels are very susceptible to developing arteriosclerosis. There is a constant degree of inflammation present in the vessel walls. So anything that stimulates or triggers an inflammatory response (eg. cigarette smoking, cholesterol, high blood sugar) can cause vasculitis which can have devastating effects.
Recently, patients who are type 2 diabetics, overweight, and taking semaglutide have been found to have an increased risk of developing a rare cause of vision loss. It’s called nonarteritic anterior ischemic optic neuropathy (NAION). At the 36-month juncture of the study, 8.9% of semaglutide patients who were diabetic reported vision problems. Those not on semaglutide had a 1.8% incidence of NAION. In non-diabetics, NAION still occurred but was 2% less common.
This type of ischemic optic neuritis is a rare phenomenon (incidence 2.3-10.2 cases per 100,000 patients), but if you acquire it, permanent vision loss is a possibility, and if it occurs during the course of trying to lose weight, it won’t matter that you’re thin if you can’t see where you’re going.
Glucagon-Like Peptide-1 receptor agonists are all the rage nowadays! They work, certainly, but if you stop taking it, you regain lost weight, or have poorly-controlled diabetes again. Plus you run a small risk of potentially serious adverse effects while you’re taking it, especially if you take it a long time. These drugs should not be used and then just forgotten. Monitoring and awareness of possible adverse effects must be done and the doctor should be on the lookout for signs of problems. Don’t prescribe and ignore—problems will follow.
References: Tucker ME, Tirzepatide Tops Semiglutide for Weight Loss Medscape Medical News 2024 July 9.
Remaly J. Semiglutide Linked to Cause of Vision Loss Medscape Medical News 2024 July 3;
Rodriguez PJ, et al. Semaglutide vs Tirzepatide for weight loss in Adults with Overweight or Obesity. JAMA Int Med 2024 July 8;.
Aronne LJ, et al. Continued Treatment with Tirzepatide for Maintenance of Weight Reduction in Adults with Obesity JAMA 2024 Jan 2;331(1):38-48.
Your right…..you can’t see if you loss weigh if you can’t see.