GLP-1 Receptor Agonists & T2DM

Glucagon-like peptide-1 receptor agonists (GLP1RAs) were originally developed for use in the treatment of T2DM. More recently, a few of these medications are also being used for weight loss in patients with obesity.

GLP1RAs bind and activate the GLP-1 receptor in a manner similar to endogenous GLP-1, which exerts its main effects by stimulating glucose-dependent insulin release from the pancreatic islets. GLP-1 has also been shown to slow gastric emptying, inhibit inappropriate post-meal glucagon release, and reduce food intake.

Outcomes

The following information is for GLP1RAs when used in treating T2DM:

DrugA1C ReductionOutcomes
(ASCVD/HF)
CKDMortality
(CV/Overall)
Dulaglutide***
(Trulicity)
-1 to -1.5Benefit/
Benefit
BenefitBenefit/
Benefit
Exenatide ER***
(Bydureon)
-1.5 to -1.6Neutral/
Neutral
UnknownBenefit/
Benefit
Liraglutide***
(Victoza)
-0.8 to -1.6Benefit/ NeutralBenefitBenefit/ Benefit
Semaglutide SC***
(Ozempic)
-1.5 to -2Benefit/ NeutralBenefitBenefit/ Benefit
Semaglutide PO***
(Rybelsus)
-0.7 to -2Neutral/ NeutralUnknownBenefit/ Unknown
Exenatide** (Byetta)-1Unknown/ UnknownUnknownUnknown/ Unknown
Tirzepatide* (Mounjaro)-2 to -2.5Unknown/ UnknownUnknownUnknown/ Unknown
***Long-acting GLP1RA (more pronounced effect on fasting glucose)
**Short-acting GLP1RA (more pronounced effect on postprandial glucose)
*Dual-acting GLP1RA and GIP receptor agonist

How to prescribe

Again, the following information is for GLP1RAs when used in treating T2DM:

AgentInitial DoseMaintenance DoseQuantityPrescribe needles?
Exenatide ER2 mg SC once weeklyN/A4 pens (3.4 mL)No
Dulaglutide0.75 mg SC once weekly1.5 mg -> 3 mg -> 4.5 mg4 pens (2 mL)No
Semaglutide SC0.25 mg SC once weekly for 4 weeks, then increase to 0.5 mg SC once weekly1 mg -> 2 mg1 pen (3 mL)No
Liraglutide0.6 mg SC once daily for 1 week, then increase to 1.2 mg SC once daily1.8 mg3 pens (9 mL)Yes
Semaglutide PO3 mg once daily for 30 days, then increase to 7 mg once daily14 mg30 tabletsN/A
Exenatide5 mcg SC BID (within 1 hour before the 2 main meals of the day, at least 6 hours apart)10 mcg5 mcg dose: 1.2 mL (1 pen)
10 mcg dose: 2.4 mL (1 pen)
Yes
Tirzepatide2.5 mg SC once weekly for 4 weeks, then increase to 5 mg SC once weekly7.5 mg -> 10 mg -> 12.5 mg -> 15 mg4 pens (2 mL)No
  • Dulaglutide:
    • Initial dose: 0.75 mg SC once weekly
    • If not meeting glycemic goals after 4 weeks, increase dose as tolerated every 4 weeks as follows: 1.5 mg SC once weekly, then 3 mg SC once weekly, then 4.5 mg SC once weekly
  • Exenatide ER:
    • Initial dose: 2 mg SC once weekly
  • Liraglutide:
    • Initial dose: 0.6 mg SC once daily for 1 week and then increase to 1.2 mg SC once daily
    • If not meeting glycemic goals after another 1-2 weeks, increase dose as tolerated to 1.8 mg SC once daily
  • Semaglutide SC:
    • Initial dose: 0.25 mg SC once weekly for 4 weeks, then increase to 0.5 mg SC once weekly
    • If not meeting glycemic goals after at least 4 weeks, increase dose as tolerated every 4 weeks as follows: 1 mg SC once weekly, then 2 mg SC once weekly
  • Semaglutide PO:
    • Take fasting, at least 30 min before breakfast or other oral medications, with no more than 4 oz of plain water
    • Initial dose: 3 mg once daily for 30 days and then increase to 7 mg once daily
    • If not meeting glycemic goals after 30 days on 7 mg dose, increase dose as tolerated to 14 mg once daily
  • Exenatide:
    • Initial dose: 5 mcg SC twice daily (within 1 hour before the 2 main meals of the day, at least 6 hours apart)
    • If not meeting glycemic goals after 4 weeks, increase dose as tolerated to 10 mcg SC twice daily
  • Tirzepatide:
    • Initial dose: 2.5 mg SC once weekly for 4 weeks, then increase to 5 mg SC once weekly
    • If not meeting glycemic goals after at least 4 weeks, increase by 2.5 mg increments every 4 weeks as needed to achieve glycemic goals. Maximum dose 15 mg SC once weekly

Local insurance Coverage

Active coverage for GLP1RAs in treating T2DM (as of the date of this blog post) in a few common insurance plans in RI:

  • NHPRI Medicaid
    • Formulary: dulaglutide (Trulicity), semaglutide SC (Ozempic), semaglutide PO (Rybelsus), tirzepatide (Mounjaro)
      • All meds require PA
    • Non-formulary: exenatide ER (Bydureon), exenatide (Byetta), liraglutide (Victoza)
  • NHP Commercial
    • Formulary: dulaglutide (Trulicity), liraglutide (Victoza), semaglutide SC (Ozempic), tirzepatide (Mounjaro)
      • All meds require step therapy and PA
    • Non-formulary: exenatide ER (Bydureon), exenatide (Byetta), semaglutide PO (Rybelsus)
  • UHC Medicaid
    • Formulary: liraglutide (Victoza), semaglutide SC (Ozempic), semaglutide PO (Rybelsus), tirzepatide (Mounjaro)
      • All meds require PA
    • Non-formulary: exenatide ER (Bydureon), exenatide (Byetta)

Blog post based on information compiled by our clinical pharmacy team!

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