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GLP-1 agonists in type 2 diabetes

Rybelsus (semaglutide) is a daily oral GLP-1 agonist for Type 2 diabetes that has A1C lowering as strong as injected Victoza (liraglutide) 1.8mg and somewhat better weight loss (-4.4kg versus -3.1kg to week 26), with similar gastrointestinal side effects. For proper oral absorption, it must be taken at least 30 minutes before the first food, beverage, or other oral medications of the day. 


  • In which patients, line of therapy, or other situations do you use Rybelsus as compared to injectable GLP-1 agonists, and when do you use an injectable GLP-1 agonist instead? 
  • In which patients, lines of therapy, or other situations do you prefer other oral classes of agents, besides metformin, to Rybelsus and why? 

  • In patients with type 2 DM and established atherosclerotic cardiovascular disease after metformin and lifestyle modifications, I advise the use of Rybelsus for patients who are unwilling or unable to self-inject glucose-lowering medications. The reasons to sometimes avoid it are the GI side effects (nausea, vomiting, abdominal pain) and it’s need to be administered at least 30 min before the first food, beverage, or other oral medications of the day and that it be taken with no more than 4 oz plain water only.

    Other reasons to avoid it include its interactions with medications including levothyroxine or bisphosphonates.

    To the second question I would use an alternative agent in diabetics without atherosclerotic cardiovascular disease
    March 25, 2022
  • I would use Rybelsus over injectable GLP1 agonists for patients who are terrified of needle, esp. the weight loss are comparable as well as the CV benefits, I may also prescribed once weekly Ozempic.
    For question 2, I will consider the SGLT2 inhibitors for the CV and renal benefits as well as BP reduction, weight loss but not as robust compared to the GLP1 agonist
    March 25, 2022
  • I will use Rebelsus in overweight and obese patients, patients who refuse injection treatment-
    The GI side effects, drug drug interactions and having to take 30 minutes before meal may limit its use in some patients.
    GLP2 agonists are preferred over GLP1 agonists for their CV benefits and will remain first line over GLP2 agonists for me
    March 25, 2022
  • Once a week Trulucity would be easier to use in patients who don’t have injection phobia rather than daily Rebelsus with its need to be taken 30 minutes before any food or beverage
    March 25, 2022
  • I would use Rybelsus in someone who is needle phobic or prefers not to inject.

    I would use other classes in patients with proven cv disease and or CKD
    March 25, 2022
  • I think Rybelsus would be an excellent alternative to those with Type II DM that have needle phobia or want to defer initiate insulin , or those with obesity and CAD and motivated to loose weight, higher A1C uncontrolled on other oral therapies;
    Patients obviously should be able to afford oral therapies as these agents are expensive; would use in some one who prefer pills over injections

    Other class of drugs are preferred in those with no significant CAD risk and those who are forgetful to take this drug on empty stomach; otherwise no reason to not use RYbelsus.
    March 26, 2022
  • For patient who absolutely hates needle, I would use Rybelsus, study showed improved hA1C by 1 to 1.3%, some weight loss although does not increase the risk of major cardiovascular (CV) events such as heart attack, stroke, or death. Other then Rybelsus, I would prefer SGLT2 inhibitors like Invokana, Jardience, Farxiga for their CV and renal benefits
    March 27, 2022
  • I use once weekly glp1 agonist in those needing more weight loss and who are otherwise not needle phobic; rybelsus is an alternative for those not willing to inject.
    April 14, 2022