Tirzepatide – A Twincretin

Tirzepatide (brand name Mounjaro) is a GIP/GLP-1 agonist produced by Eli Lilly and company that was recently approved by the FDA for the treatment of type 2 diabetes. It is a once-weekly injection that helps to control blood sugar levels and can also help with weight loss. Tirzepatide has been shown to be effective in reducing A1c levels and improving glycemic control.

What is a twincretin

A twincretin is a GIP and GLP-1 analog that has shown promise in early studies as a potential treatment for diabetes. “Twincretin” has gained recent traction in diabetology and refers to medications with a  both GIP and GLP-1 agonist properties. This allows twincretins at pharmacologic doses to exert a profound “incretin effect.” GIP and GLP-1 are hormones that play a role in glucose metabolism, and by mimicking their effects, a twincretin may help to regulate blood sugar levels and improve weight loss. Early research on twincretins has shown that they can improve insulin sensitivity and reduce fasting blood sugar levels in people with type 2 diabetes. However, more research is needed to confirm these effects and to determine if twincretins are safe and effective for long-term use. If proven effective, twincretins could become a valuable addition to not only the current diabetes treatment arsenal but also obesity management.

surmount infographic

Background

The results of the landmark SURMOUNT-1 study were published in the New England Journal of Medicine on June 4, 2022. The results were also presented at the 82nd scientific session of the American Diabetes Association in New Orleans, Louisiana.

Study Abstract

The SURMOUNT-1 trial was a study to assess the safety and efficacy of tirzepatide, a novel GIP/GLP-1 dual agonist in improving weight loss among individuals with obesity.

The inclusion criteria for the study

  • BMI ≥30 kg/m2 or 27 kg/m² and previous diagnosis with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease.
  • Failure of prior dietary approaches to losing weight

Exclusion criteria for the study

  • A history of diabetes Mellitus
  • Greater than 5kg weight loss within a 3-month pre-randomization stage
  • Secondary causes of obesity such as monogenic etiology or other hormonal derangements
  • History of pancreatitis
  • Family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
  • History of major depressive disorder.

The mean body weight of study subjects was 104.8kg with a corresponding BMI of 38. The trial randomized 2539 individuals with obesity to once-weekly subcutaneous injections of 5mg, 10mg, 15mg, or matching placebo over a 72-week period.

In the SURMOUNT-1 trial, all three doses of tirzepatide demonstrated substantial clinically meaningful and statistically significant body weight reductions compared to placebo. Weight reductions were 15%,19.5% and 20.9% for tirzepatide doses 5, 10 and 15mg respectively.

More importantly, a prespecified weight reduction of greater than 5% was achieved in 91% of individuals who were on the maximum dose of tirzepatide (15mg once weekly). Also, up to 57% of participants achieved a ≥20% reduction in body weight (compared to baseline) at the conclusion of the study. Furthermore, up to 35% of study participants achieved a greater than 25% reduction in body weight. Finally, weight reduction was sustained across all dosing categories for the duration of the study. All pre-specified cardio-metabolic endpoints improved for all patients on tirzepatide.

Conclusion

Obesity is a chronic, treatable disease with various cardiometabolic comorbidities, including hypertension, diabetes mellitus, hyperlipidemia, fatty liver disease, and obstructive sleep apnea, to mention a few. Weight loss, no matter how modest, can help mitigate cardiometabolic complications of obesity.

The results of the SURMOUNT-1 study provide new hope for patients with obesity and will undoubtedly expand on the available armamentarium to treat the condition.

Tirzepatide was approved by the United States Food and Drug Administration on May 13, 22.

Disclaimer

The opinions expressed here represent the views of a practicing hormone specialist (endocrinologist) and must not substitute the advice of your health care provider. This blog post is written for a non-medical audience interested in learning more about hormonal disorders. The author has no commercial conflicts of interest to declare. Also, read our privacy policy.

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