Lilly launches Mounjaro (tirzepatide), offers new treatment option for obesity and type 2 diabetes

Eli Lilly and Company (India) announced the launch of Mounjaro in single-dose vial presentation following the marketing authorisation from the Central Drugs Standard Control Organization (CDSCO). It is a treatment for obesity, overweight, and type 2 diabetes that activates both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) hormone receptors. 

Mounjaro is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m2 or greater (obesity) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition. Mounjaro is also indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. 

Tirzepatide was evaluated in two robust global clinical development programmes: the SURMOUNT – 1 trials for chronic weight management and the SURPASS trials for type 2 diabetes. 

In SURMOUNT-1, a study of 2,539 adults with obesity, or excess weight and weight-related medical problems not including diabetes, people taking Mounjaro as an adjunct to diet and exercise experienced substantial weight loss compared with placebo at 72 weeks. At the highest dose (15 mg), people taking Mounjaro lost on average 21.8 kg, while at the lowest dose (5 mg), people lost on average 15.4 kg (compared to 3.2 kg on placebo) (1,2). Additionally, 1 in 3 patients taking Mounjaro at the highest dose lost over 26.3 kg (25 per cent of body weight), compared to 1.5 per cent on placebo, according to data not controlled for type 1 error (1,2). In summary, Mounjaro significantly reduced weight by up to 21.8 kg in the SURMOUNT-1 study (1,2).

In phase 3 SURPASS programme, efficacy was evaluated for Mounjaro 5 mg, 10 mg and 15 mg used alone or in combination with commonly prescribed diabetes medications, including metformin, SGLT2 inhibitors, sulfonylureas and insulin glargine. Participants in the SURPASS programme achieved average A1C reductions between 1.8 per cent and 2.1 per cent for Mounjaro 5 mg and between 1.7 per cent and 2.4 per cent for both Mounjaro 10 mg and Mounjaro 15 mg over the period of 40 weeks (3-6). Overall, the program demonstrated that Mounjaro, whether used alone or with other diabetes medications, reduced A1C by up to 2.4 per cent (3-6).

India has about 101 million people living with diabetes and nearly half of these in the adult patients category are being inadequately treated with suboptimal glycemic control (10). Obesity, a chronic relapsing disease, is a major risk factor for diabetes, is linked to over 200 health complications, including hypertension, dyslipidemia, coronary heart disease, and obstructive sleep apnea (11,12). As of 2023, adult obesity prevalence in India stood at around 6.5 per cent, affecting nearly 100 million people (13).

“Obesity and diabetes are recognised as serious conditions linked to various life-limiting health complications, making effective and sustained treatment critical. We are thrilled to introduce Mounjaro in India to address these unmet medical needs. Mounjaro may offer a new approach to metabolic health management, providing healthcare providers with an innovative option to treat these diseases.” said Dr Manish Mistry, Senior Medical Director, Lilly India.

Once-a-weekly, prescription-based medicine, Mounjaro is a single molecule that selectively binds to and activates both GIP and GLP-1 receptors, which are natural incretin hormones. In a glucose-dependent manner, Mounjaro improves first-phase and second-phase insulin secretion, and reduces glucagon levels; it also improves insulin sensitivity and delays gastric emptying (14). GIP receptors and GLP-1 receptors are both expressed in important areas of the brain that regulate appetite. Mounjaro reduces food intake, body weight, and decreases fat mass by regulating appetite; moreover, Mounjaro has been demonstrated to regulate lipid utilization (14). Mounjaro (tirzepatide) has already had a tremendous impact on millions of people living with type 2 diabetes and obesity, respectively.

References:

1. Mounjaro. Prescribing Information for India.
2. Jastreboff AM, Aronne LJ, Ahmad NN, et al; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216.
3. Rosenstock, J, et. al. Efficacy and Safety of Once Weekly Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist Versus Placebo as Monotherapy in People with Type 2 Diabetes (SURPASS-1). Abstract 100-OR. Presented virtually at the American Diabetes Association’s 81st Scientific Sessions; June 25-29.
4. Rosenstock, J, et. al. (2021). Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-155. doi: 10.1016/S0140-6736(21)01324-6.
5. Frías JP, Davies MJ, Rosenstock J, et al; for the SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6) (suppl):503-515. doi: 10.1056/NEJMoa2107519
6. Frias, J.P. Efficacy and Safety of Tirzepatide vs. Semaglutide Once Weekly as Add-On Therapy to Metformin in Patients with Type 2 Diabetes. Abstract 84-LB. Presented virtually at the American Diabetes Association’s 81st Scientific Sessions; June 25-29.
7. Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398(10300):583-598. doi: 10.1016/S0140-6736(21)01443-4
8. Del Prato S, Kahn SE, Pavo I, et al; for the SURPASS-4 Investigators. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021;398(10313):1811-1824. doi: 10.1016/S0140-6736(21)02188-7
9. Dahl D, Onishi Y, Norwood 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. doi:10.1001/jama.2022.0078
10. Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17) – The Lancet Diabetes & Endocrinology                                                                                      
11. Waters H, Graf M. America’s Obesity Crisis: The Health and Economic Costs of Excess Weight. Milken Institute; 2018. Accessed February 20, 2024. https://milkeninstitute.org/sites/default/files/reports-pdf/Mi-Americas-Obesity-Crisis-WEB_2.pdf
12. Wolk R, Shamsuzzaman AS, Somers VK. Obesity, sleep apnea, and hypertension. Hypertension. 2003;42(6):1067-1074. doi:10.1161/01.HYP.0000101686.98973.A3
13. IQVIA analysis and projection based on National Family Health Survey (NFHS-5), India, 2019-20 and Data from Global Observatory (World Obesity)- https://data.worldobesity.org/country/india-95/#data_economic-impact
14. Rosenstock J, Wysham C, Frias JP, et al. Lancet 2021; 398(10295): 143-155.