Help Navigate Common Hurdles With GLP-1 Agonists

Questions are rolling in about GLP-1 agonists...dulaglutide (Trulicity), liraglutide (Victoza), semaglutide (Ozempic, etc), etc.

It’s partly because these meds are a first-line option for type 2 diabetes with compelling indications...such as CV or kidney disease.

Plus semaglutide or the dual agonist tirzepatide (Zepbound, etc) seem to be the most effective meds for managing overweight or obesity.

Be ready to navigate common hurdles and guide appropriate use.

Expect GLP-1 agonist shortages to continue...due to high demand.

If needed, temporarily step down to a lower dose.

Or change GLP-1 agonists if necessary. Lean toward a med given at the same interval...and consider switching to a comparable dose.

For example, if a patient using semaglutide 0.5 mg weekly for type 2 diabetes can’t get it due to shortages...consider switching to dulaglutide 1.5 mg weekly, beginning on the date the next dose is due.

When starting GLP-1 agonists or stepping up doses, counsel to expect modest, temporary GI upset (nausea, etc).

Start low and go slow...to improve tolerability.

For example, start tirzepatide at 2.5 mg weekly and increase by 2.5 mg every 4 weeks as tolerated...up to a max of 15 mg/week.

Keep in mind, it’s okay to slow the titration if patients still have adverse effects.

To help limit nausea, encourage patients to eat smaller meals...consume food slowly...and stop eating before they feel full.

Think about trying a short-term med to relieve symptoms if needed...such as ondansetron for nausea or loperamide for diarrhea.

If that’s still not enough, consider a temporary dose reduction...or settle on a lower than max dose for tolerability.

Educate to promptly report severe GI pain. It can be a red flag for rare pancreatitis, gallbladder issues, or bowel obstruction.

Be alert for potential interactions. For example, tirzepatide labeling cautions about possible reduced efficacy of oral contraceptives. This is due to delayed gastric emptying...which lessens with time.

Discuss switching to a non-oral (ring, IUD, etc) option or adding a barrier method for 4 weeks after starting and each titration.

Be aware, FDA’s recent analysis doesn’t confirm a link between GLP-1 agonists and suicide risk...but monitoring is ongoing. Continue to advise patients to report mood changes, suicidal thoughts, etc.

Use our resources, Drugs for Type 2 Diabetes and Weight Loss Products, for efficacy comparisons, safety considerations, and more.

Key References

  • American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024. Diabetes Care. 2024 Jan 1;47(Suppl 1):S158-S178.
  • Almandoz JP, Lingvay I, Morales J, Campos C. Switching Between Glucagon-Like Peptide-1 Receptor Agonists: Rationale and Practical Guidance. Clin Diabetes. 2020 Oct;38(4):390-402.
  • Anderson J, Gavin JR 3rd, Kruger DF, Miller E. Optimizing the Use of Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes: Executive Summary. Clin Diabetes. 2022 Summer;40(3):265-269.
  • le Roux CW, Zhang S, Aronne LJ, et al. Tirzepatide for the treatment of obesity: Rationale and design of the SURMOUNT clinical development program. Obesity (Silver Spring). 2023 Jan;31(1):96-110.
  • Ruder K. As Semaglutide's Popularity Soars, Rare but Serious Adverse Effects Are Emerging. JAMA. 2023 Dec 12;330(22):2140-2142.
Prescriber Insights. February 2024, No. 400201



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