ADA journal publishes practical guidance on switching between GLP-1 drugs

The American Diabetes Association's journal Clinical Diabetes published a review in October 2020 that offers practical guidance for clinicians on switching patients between GLP-1 receptor agonists ^[1]. The paper was led by Dr. Jaime P. Almandoz of UT Southwestern Medical Center in Dallas, with coauthors from Hofstra/Northwell University and the University of Texas Health Science Center at San Antonio ^[1].

Pharmacy data cited in the review suggest that up to one-fourth of patients switch from their first GLP-1 receptor agonist to another glucose-lowering medicine after the first year of treatment, and some of those patients move to a different GLP-1 ^[1]. The authors write that such switches may happen for several reasons, but that practical guidance on how to manage the transition safely and effectively is scarce ^[1]. Their recommendations draw on a PubMed search — 161 results for GLP-1 switching terms and 97 for once-daily versus once-weekly dosing terms — supplemented by their own clinical experience ^[1].

The review stresses that these drugs differ widely even though they belong to one class. Five molecules are marketed in the United States: dulaglutide, liraglutide and semaglutide, which are analogs of human GLP-1, and exenatide and lixisenatide, which are exendin-based ^[1]. Albiglutide was also approved but has been withdrawn for commercial reasons ^[1]. Half-lives in the review's comparison table range from about 2.4 hours for exenatide to roughly 7 days for semaglutide ^[1]. Exenatide is given twice daily, liraglutide and lixisenatide once daily, and dulaglutide, subcutaneous semaglutide and extended-release exenatide once weekly ^[1].

The dosing schedules are not interchangeable. In the table, subcutaneous semaglutide starts at 0.25 mg and rises to 0.5 mg after four weeks, then to 1 mg after another four weeks if needed; dulaglutide starts at 0.75 mg and can increase to 1.5 mg; liraglutide starts at 0.6 mg for one week, then 1.2 mg, with 1.8 mg as a further step ^[1]. Oral semaglutide, then newly approved in the United States, is dosed at 3 mg for 30 days, then 7 mg, and escalated to 14 mg after another 30 days if required ^[1]. It must be taken on an empty stomach with no more than 4 fluid ounces (120 mL) of plain water and at least 30 minutes before the first food, beverage or other oral medicine of the day ^[1].

Why it matters for patients

Switching from one GLP-1 to another is not a like-for-like swap. The medicines differ in how long they stay in the body, how often they are injected or taken by mouth, and what rules apply around meals ^[1]. A prescriber weighing a change has to account for all of that, and the review's guidance is written for clinicians rather than patients; it does not give patient-facing instructions ^[1]. The authors are also explicit that they supplement the available data with clinical experience, which means some of their suggestions are not backed by head-to-head trials of one GLP-1 against another ^[1]. Cost, insurance coverage and side effects are common triggers for these decisions, but the review does not rank those reasons or say how often each one applies. What a given patient's transition looks like depends on which two drugs are involved, and there is no FDA-approved conversion chart between GLP-1 molecules.

What happens next

No date has been set for updated guidance, and the review does not propose one ^[1]. Whether regulators or professional groups later publish a standardized conversion table between GLP-1 molecules has not been reported. Until then, the review's authors present their recommendations as practical suggestions for prescribers rather than a fixed protocol ^[1].