Tirzepatide: A Dual GLP-1/GIP Receptor Agonist for the Treatment of T2D

Authors: Ashley Wagnild, PharmD Candidate 2024, Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP

Department of Pharmacotherapy

College of Pharmacy and Pharmaceutical Sciences

Washington State University

A 54-year-old man was referred to the pharmacotherapy clinic by his primary care provider (PCP) for a therapy consult. The patient had a past medical history significant for type 2 diabetes, hypertension, dyslipidemia, and obesity. When asked about his priorities for care, he desired to decrease the frequency of his hypoglycemic events and to lose weight. The patient reports blood glucose readings ranging from 52-65 mg/dL two or three times weekly with pronounced rebound hyperglycemia. He had a private insurance plan with low copays. His current A1C was 7.9%. He weighed 240 pounds and had a BMI of 34.4 kg/m².

Medication regimen at time of consult:

• Janumet XR (Sitagliptin 100mg – Metformin 1000mg) once daily in the morning
• Glyburide 5 mg once daily in the morning
• Insulin glargine (Lantus) 60 units subcutaneously once daily in the evening
• Atorvastatin 40 mg once daily in the evening
• Lisinopril 40 mg once daily in the morning

As expressed by the patient, his highest priorities included minimizing hypoglycemia and weight loss. He was currently managed with basal insulin and a sulfonylurea – both of which were likely contributing to both his frequent hypoglycemia and weight gain.

Because the patient was comfortable with self-injection, we felt he was a good candidate for a non-insulin injectable agent with low hypoglycemia risk, good glycemic efficacy, and the potential for weight loss. Tirzepatide (Mounjaro) was approved in May 2022 to improve glycemic control in adults with type 2 diabetes.¹ Tirzepatide is sometimes referred to as a “twincretin” agent because it activates both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors.² Data available to date indicate that tirzepatide has unmatched effectiveness for both A1C and weight reduction.² When compared to 1mg once weekly of injectable semaglutide, tirzepatide treatment resulted in greater reductions in both A1C and weight from baseline in the SURPASS-2 clinical trial.³ Tirzepatide has also demonstrated benefit in improving glycemic control when added to background insulin glargine therapy in people with type 2 diabetes with inadequate glycemic control.⁴

Recommendations made:

• Initiate tirzepatide 2.5 mg subcutaneously once weekly for 4 weeks, then increase to 5 mg once weekly if tolerated. May increase dose by 2.5 mg/week every 4 weeks if needed to achieve individualized glycemic goals up to a maximum weekly dose of 15 mg.
• Discontinue Janumet XR and start metformin ER 1,000 mg once daily. Because tirzepatide is being added, continued benefit from the DPP-4 inhibitor is unlikely and should be discontinued.
• Discontinue glyburide to decrease hypoglycemia risk.
• The patient was counseled about hypoglycemia prevention, hypoglycemia treatment recommendations, and lifestyle recommendations to assist with weight loss (e.g., healthy diet and increased physical activity).
• The patient was scheduled for a 1-week follow up phone call and asked to monitor his blood glucose and contact the clinic with any severe tolerability issues or hypoglycemic events.

Lessons learned:

• Tirzepatide is a dual GLP-1/GIP receptor agonist with robust glycemic and weight lowering effects.
• Tirzepatide has demonstrated benefits in improving glycemic control in adults with type 2 diabetes with inadequate glycemic control despite background basal insulin therapy.
• When adding tirzepatide to an existing medication regimen, adjustments to background insulin and/or sulfonylurea therapy should be considered to prevent treatment-emergent hypoglycemia.

References:

1. Mounjaro (tirzepatide) injection. Prescribing information. Eli Lilly and Company. Indianapolis, IN. September 2022.
2. Nauck MA, D’Alessio DA. Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regarding glycaemic control and body weight reduction. Cardiovasc Diabetol. 2022;21(1):169.
3. Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385:503-515.
4. Dahl D, Onishi Y, Norwwod P, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: The SURPASS-5 randomized clinical trial. JAMA. 2022;327(6):534-545.