Mounjaro™ (tirzepatide) is a dual-targeted, injectable, sustained-release therapy indicated for the management of type 2 diabetes (T2D) in adults as an adjunct to diet and exercise.
Developed by US-based pharmaceutical company Eli Lilly, Mounjaro is the first and only once-weekly glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist to improve blood glucose levels in adults with T2D.
Mounjaro is available in six doses as a clear, colourless to slightly yellow solution. It is available in pre-filled single-dose auto-injector pens for subcutaneous delivery.
Mounjaro regulatory approvals
In May 2022, the US Food and Drug Administration (FDA) approved Mounjaro for the T2D indication after receiving priority review designation. In July that year, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the approval of Mounjaro for the treatment of type 2 diabetes mellitus.
The drug received marketing authorisation in the European Union in September 2022, also receiving approval in Japan in the same month. Mitsubishi Tanabe Pharma Corporation (MTPC) distributes and sells Mounjaro in Japan according to its sales collaboration agreement with Eli Lilly Japan, which was signed in July 2022. The drug is administered using ATEOS®, a single-use autoinjector device, in Japan.
In October 2022, the FDA granted Fast Track designation for tirzepatide to evaluate it for the treatment of obesity, or overweight with weight-related comorbidities, in adults. Eli Lilly intends to begin a rolling submission of a new drug application (NDA) for the drug for these conditions. The NDA will be based primarily on the results of two Phase III clinical trials, SURMOUNT-1 which is complete, and SURMOUNT-2 which is expected to be completed by the end of April 2023.
Type 2 diabetes signs and symptoms
T2D is a chronic and progressive condition in which blood sugar regulation in the body is impaired, causing excessive sugar circulation in the bloodstream. High blood sugar levels can lead to circulatory, nervous, and immune system disorders.
The most common form of diabetes, T2D develops slowly and individuals with the condition can remain asymptomatic for years. Signs and symptoms of the disease can include increased thirst and hunger, frequent infection and urination, unintended weight loss, blurred vision, fatigue, slow-healing sores, and numbness or tingling sensations in the hands and feet.
Mounjaro’s mechanism of action
Mounjaro (tirzepatide) is a single molecule that selectively binds to and activates both the GIP and GLP-1 receptors to target GIP and GLP-1, the native incretin hormones.
The activation of these receptors improves the secretion of both first and second-phase insulin and reduces glucagon levels, both in a glucose-dependent manner.
Clinical trials on Mounjaro
The FDA’s approval of Mounjaro was based on positive outcomes from a Phase III SURPASS programme that included five clinical trials, namely SURPASS-1, SURPASS-2, SURPASS-3, SURPASS-4 and SURPASS-5.
In SURPASS-1, Mounjaro was studied as a monotherapy. In SURPASS-2, SURPASS-3 and SURPASS-4, the drug was studied as an add-on to the common diabetes medications metformin, sulfonylureas, and/or sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors). For SURPASS-5, Mounjaro was evaluated in combination with basal insulin with or without metformin.
Three doses of Mounjaro, namely 5mg, 10mg and 15mg, were used for evaluating the drug’s efficacy in the SURPASS programme. The doses were administered subcutaneously once weekly for comparison with placebo (SURPASS-1), semaglutide 1mg (SURPASS-2), insulin degludec (SURPASS-3), and/or insulin glargine (SURPASS-4).
These doses, in combination with basal insulin with or without metformin, were compared with placebo in T2D patients in the SURPASS-5 clinical study.
Patients with T2D who participated in the SURPASS programme achieved reductions of between 1.8% and 2.1% in their blood glucose levels on an average for Mounjaro 5mg, and between 1.7% and 2.4% for both 10mg and 15mg doses of Mounjaro.
Mounjaro delivered superior blood glucose level reductions against all comparators in the SURPASS programme. Use of the drug also led to significantly greater weight loss in patients than other comparators. Patients treated with 5mg of Mounjaro lost 12lb of weight, while those given a 15mg dose saw their weight reduce by 25lb.
The most common side effects reported in patients during the clinical trials were nausea, diarrhoea, decreased appetite, vomiting, constipation, indigestion, and abdominal pain.