Mounjaro® (tirzepatide), Lilly’s innovative drug for treating type 2 diabetes (DM2) or for weight control in obese people, is now available in Spain. This drug, administered subcutaneously weekly, will be available from July 1 in Spanish pharmacies, always under medical prescription, in doses of 5 and 10 mg.
Due to its proven efficacy, tirzepatide has been approved for two indications. On the one hand, as a treatment for DM2 and, on the other, for weight control in overweight people with a body mass index (BMI) >27kg/m2 and at least one complication resulting from excess weight, or obesity (BMI) >30 kg/m2)1.
This is the first drug in a new therapeutic family that acts on GIP and GLP-1 receptors.1Its mechanism of action, in addition to promoting glycemic control, decreases appetite, increases the feeling of satiety and reduces excess fat, including visceral fat around the waist.4. Furthermore, in people with DM2, it improves glycemic control through multiple mechanisms that include increased insulin secretion, decreased glucagon secretion, and improved insulin sensitivity.1.
In clinical studies in people with T2DM, tirzepatide has demonstrated excellent glycemic control (up to 87% of patients achieved glycated hemoglobin (HbA1c) levels of 6.5% or lower compared to 66.2% of those treated with semaglutide 1 mg), and even around 50% achieved levels similar to those of a person without diabetes (HbA1c ≤5.7%) compared to 19.7% who achieve this with semaglutide.1,2with average weight losses of up to 12.4kg with tirzepatide versus 6.2kg with semaglutide, all with a favorable safety profile.1,2
In overweight and obese people without diabetes, tirzepatide showed a Average weight reduction of up to 22.5% (23.6 kg) at week 72 and, in addition, 4 out of 10 patients achieved a weight loss equal to or greater than 25%1.4. All this with a high response rate: 96% of patients achieved a reduction equal to or greater than 5% after 72 weeks of treatment1.4.
The clinical development of tirzepatide has had a robust clinical trial program, known as SURPASS (in people with DM2) and SURMOUNT (in people with obesity and overweight, without diabetes).), “in which the powerful effect of the molecule has been demonstrated in terms of glycemic control, even achieving normalization of HbA1c levels in up to 51% of people with DM2 treated, and weight loss with decreases of around 20% with doses of 10 and 15 mg/week in obesity. These data are close to what is achieved after bariatric surgery. In addition, beneficial effects on different cardiovascular risk factors are observed, although the specific results of the cardiovascular effects will be known later”, indicates the Dr. Javier Escalada, president of the Spanish Society of Endocrinology and Nutrition Foundation (FSEEN).
Indicated for type 2 diabetes
Tirzepatide is the first molecule in its therapeutic class approved for the treatment of DM2 when sufficient control is not achieved with diet and exercise alone, and has demonstrated a reduction in HbA1c and weight superior to treatments from other therapeutic classes (including GLP-1 receptor agonists) at all doses studied.1.3.
The efficacy and safety information as a treatment for DM2 comes from the SURPASS clinical trial program, which studied its use both as monotherapy and in combination with other drugs used to control DM2.1.3The SURPASS-2 phase 3 clinical trial was a 40-week, head-to-head comparison study with semaglutide 1 mg. SURPASS-2 included 1,879 patients with a mean baseline HbA1c of 8.28% and a diagnosis of diabetes for a mean of 8.6 years.2.
Indicated for weight control in people with obesity
The use of tirzepatide as a treatment for weight control in overweight adults with BMI >27kg/m2 and at least one weight-related complication, or obesity (BMI) >30 kg/m2) has been studied in the SURMOUNT clinical program.
SURMOUNT-1 is a multicenter, randomized, double-blind, parallel, placebo-controlled Phase 3 clinical trial that compared the efficacy and safety of tirzepatide 5 mg, 10 mg, and 15 mg versus placebo, both as an adjunct to a low-calorie diet and increased physical activity in overweight or obese adults with at least one of the following complications: hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease.1.4.
In addition to the weight control already mentioned, in the participants included in this clinical trial, with tirzepatide a benefit is observed in key cardiometabolic parametersgenerating reductions in waist circumference ranging from 14.6 to 19.9 cm, reductions of the triglycerides (24.3 – 31.4%), decrease in the blood pressure (both systolic and diastolic) and a positive impact on blood pressure levels. cholesterol (with improvements in HDL and reductions in LDL)1.4.
Weight loss equal to or greater than 15% is associated with a reduction in the risk of cardiovascular mortality and with benefits in complications related to excess weightas various medical examinations have concluded5.6.
The impact of obesity
As she remembers Dr. Mar Malagón, president of the Spanish Society of Obesity (SEEDO), “Obesity is a chronic, relapsing disease that affects more than 18% of the adult population in Spain. Scientific evidence shows that it is a complex and multifactorial disease, influenced by biological and genetic factors, socioeconomic and environmental factors, and hours of sleep. Research has also been essential to identify the intrinsic factors that regulate intake and body weight, which has served as a basis for the development of compounds with therapeutic utility that open the door to optimism for people who suffer from this disease.”
In addition, people with obesity have a higher risk of suffering more than 200 complications7.8 as “cardiovascular diseases, type 2 diabetes mellitus, lipid disorders, metabolic liver disease (the leading cause of cirrhosis in our country), as well as various chronic respiratory pathologies, infertility, without forgetting very prevalent cancers: breast, colorectal, kidney, liver, ovarian, etc.”, add the Dr. Alfredo Michán Doña, specialist in Internal Medicine and coordinator of the Diabetes, Obesity and Nutrition group of the Spanish Society of Internal Medicine (SEMI).
The expert stresses that “Knowledge of its approach and treatment is essential for every clinical physician”since, in addition, obesity increases the risk of premature death and compared to adults with a healthy weight, people with obesity have 12 times more risk of developing 4 or more related diseases.7.
“The commercialization of tirzepatide represents a milestone in the treatment of people with type 2 diabetes and obesity. It is a disruptive innovation, which reflects Lilly’s vocation to research and develop medicines that represent a qualitative leap in the treatment of diseases that impact the life expectancy and quality of life of patients,” affirms the Dr. José Antonio Sacristán, medical director of Lilly Spain. “We are very proud of Spain’s participation in Tirzepatide’s clinical research programmes. Of the more than 10,000 patients who have participated in the clinical development of Tirzepatide, 95 centres (35 of them in obesity studies) and 1,128 patients have participated in Spain, which reflects the enormous quality of our healthcare system and of Spanish researchers.”
About Tirzepatida
The use of tirzepatide is approved by the European Medicines Agency for the treatment of weight control in overweight people over 18 years of age (BMI ≥27 kg/m2 a <30kg/m2) and at least one comorbidity related to weight or obesity (BMI ≥30 kg/m2), along with a low-calorie diet and increased physical activity.1
This drug is also approved for the treatment of adults with insufficiently controlled type 2 diabetes, as monotherapy in those patients who cannot take metformin or as an adjunct to other medications for the treatment of diabetes.1
It is the first therapeutic option of its kind that acts differently by activating the GIP hormone receptors and the GLP-1 hormone receptors.1
It will be available in pharmacies from July 1 in 2.5, 5, 7.5 and 10 mg doses (the 2.5 and 7.5 mg doses are escalating doses; the 5 and 10 mg doses are maintenance doses). The 15 mg dose is not yet available in Spain.
References:
1. Mounjaro® SmPC. Available at: https://image.mc.lilly.com/lib/fe8c127270660c7571/m/12/b90bd414-654c-4aae-a2d2-6c27a2c922e4.pdf Last accessed: June 2024.
2. Frias JP. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515.
3. From Block M, et al. Tirzepatide for the treatment of adults with type 2 diabetes: An endocrine perspective. Diabetes Obes Metab. 2023;25:3–17.
4. Jastreboff, A, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387:205-216.
5. Sundström J, et al. Weight Loss and Heart Failure: A Nationwide Study of Gastric Bypass Surgery Versus Intensive Lifestyle Treatment. Circulation. 2017;135(17):1577-1585.
6. Ryan DH, et al. Weight loss and improvement in comorbidity: differences at 5%, 10%, 15%, and above. Curr Obes Rep. 2017;6(2):187-194
7. Kivimäki M, Strandberg T, Pentti J, et al. Body mass index and risk of obesity-related complex multimorbidity: an observational multicohort study. Lancet Diabetes Endocrinol. 2022;10(4):253-263.
8. Michalowska J, et al. Incretin Hormones in Obesity and Related Cardiometabolic Disorders: The Clinical Perspective Nutrients. 2021;13(2):351.
Fountain: Ogilvy