Safety, cost and more: The issues PCPs should consider when prescribing GLP-1s
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Key takeaways:
- GLP-1s are a popular medication for obesity, type 2 diabetes or both, with many variants on the market.
- Experts broke down some of the variables PCPs should consider when prescribing these medications.
There are many important factors primary care providers must consider when prescribing popular anti-obesity medications, according to experts.
GLP-1 receptor agonists (GLP-1 RAs) are “a diverse group of medications” that treat CVD, diabetes and obesity, Harold Edward Bays, MD, president-elect of the Obesity Medicine Association, told Healio.
“The prescribing and administration of GLP-1 RA is not a ‘one-size-fits-all’ situation,” he said. “These drugs vary in the mode of their administration, dose and dose escalation. Some GLP-1 RAs have an FDA-approved indication to treat type 2 diabetes mellitus. Some GLP-1 RAs have an FDA indication to treat obesity. Other GLP-1 RAs have an approved indication to treat type 2 diabetes mellitus and reduce the risk of cardiovascular events in adults with type 2 diabetes mellitus and established CVD, while yet others have an approved indication to reduce the risk of cardiovascular events in adults with established CVD and either obesity or overweight.”
Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician scientist at Massachusetts General Hospital and Harvard Medical School, stressed that GLP-1 is a naturally occurring hormone, and GLP-1 RAs simply augment something already in human bodies.
“We have to recognize that each and every human [who] exists has GLP-1 housed within our bodies. For those of us who happen to be leaner at baseline, we have more GLP-1s in our body ... because that sends more satiety signals to our brain,” Stanford said. “I just want us to be mindful of that because most of us think we're just giving something to some people that's just contrived, but it is derived from something that's already inherent in each of us.”
Nevertheless, it can be difficult to navigate the sea of options PCPs have when choosing a medication for their patients with obesity, type 2 diabetes or both.
What’s on the market?
Two of the most popular GLP-1 RAs are both subcutaneous semaglutide. Ozempic (Novo Nordisk), a weekly injection for adults with type 2 diabetes, and Wegovy (Novo Nordisk), a weekly injection for patients with overweight or obesity and at least one weight-related comorbid condition, have skyrocketed in popularity recently. However, they are not the only options available.
Bays and Stanford discussed several other notable GLP-1 RAs on the market in the United States:
- Exenatide (Byetta, Eli Lilly), which treats type 2 diabetes in adults;
- Exenatide extended-release (Bydureon BCise, AstraZeneca), a weekly injection that Bays said “is a longer-acting version of Byetta”;
- Semaglutide tablets (Rybelsus, Novo Nordisk), an oral tablet version of semaglutide for type 2 diabetes;
- Liraglutide (Saxenda, Novo Nordisk), a daily injection for patients with obesity;
- Dulaglutide (Trulicity, Eli Lilly), a weekly injection for patients with type 2 diabetes aged 10 years and older; and
- Liraglutide (Victoza, Novo Nordisk), a daily injection for patients with type 2 diabetes aged 10 years and older.
Additionally, tirzepatide medications are known as dual agonists, so they also contain glucose-dependent insulinotropic polypeptide Bays said. These medications include the obesity treatment Zepbound and Mounjaro for the treatment of diabetes (both manufactured by Eli Lilly).
Stanford said liraglutide was the “first generation” of these anti-obesity medications and confers the least total body weight loss — roughly 6.5%. Semaglutide, the second generation, confers about 14.5% total body weight loss, and dual agonists confer about 22.5% total body weight loss, she said.
Apart from the weight loss percentages, the medications are indistinguishable from each other, Stanford said.
Safety
Each GLP-RA generally has “similar adverse side effect profiles,” Bays said, “which differ from other anti-obesity medications.”
Stanford said some of key adverse effects include constipation, vomiting, nausea and low blood sugar, which is “mostly due to people just not having a desire to eat.”
However, the overall safety of these medications has been a major question mark for many health care professionals.
Earlier this year, the FDA investigated reports of alopecia, suicidal ideation and aspiration with use of Ozempic, Wegovy, Mounjaro, Zepbound and Saxenda. Shortly thereafter, the agency found no evidence that the medications caused suicidal ideations and aspirations.
In further review, Jingchuan Guo, MD, PhD, and colleagues recently published a target trial on GLP-1 RAs and the associated risk for suicidal ideation and behaviors among older adults with type 2 diabetes. The study, published in the Annals of Internal Medicine, included 43,209 pairs of patients.
“Among their many mechanisms of action, GLP-1 RAs are believed to reduce appetite by changing reward effects in the brain, and there is some recent concern that GLP-1 RAs may increase suicidal thoughts and risk,” Guo said. “The study did not find clear increases in risk for suicidal behaviors associated with the GLP-1-RA class of medications among older adults when compared with SGLT2i or DPP4i medications.”
However, Guo noted that “the estimates were imprecise, and researchers could not rule out a modest increase in risk,” so more research is necessary to further evaluate this potential risk.
Accessibility
Bays stressed that PCPs should examine the prescribing information and clinical trial results for each GLP-1 RA.
“The take-home message for PCPs is the need to become educated on the different types of GLP-1 RAs, their different doses, and their different FDA-approved specific indications at the doses prescribed,” he said. “PCPs should also be aware of potential side effects of these medications, how best to monitor for these side effects and practical ways to.”
Aside from safety and mechanisms of action, there are other things PCPs should consider, according to Bays and Stanford.
For example, Bays noted that “costs do vary, which plays a role in prescribing,” so accessibility issues can also factor into PCPs’ decisions.
Comparable medications like Wegovy and Zepbound are both likely to be priced at more than $1,000, “which is significantly cost prohibitive,” Stanford said.
“That’s been one of the major issues,” she added. “There’s an equity and access issue. Patients [who] come from low socioeconomic positions just aren’t going to be able to afford them. Even if you can afford them, you just can’t get them a lot of times. We had, almost for 2 years, a major issue with ... a shortage.”
Patients who have a lower socioeconomic status and members of underrepresented racial and ethnic populations are less likely to obtain GLP-1 RAs, “which is unfortunate, particularly as a member of one of these groups,” Stanford said.
“It hurts my heart to know that we just can’t often give access to these individuals,” she added. “I want to make sure that we treat obesity particularly like we do other disease processes, and not assume that this patient population deserves their fate. We don't do that with other disease processes. I just hope that at some point in my lifetime that we begin to treat this patient population with the same dignity and respect that we do with other disease processes.”