Tirzepatide Shows Significant Improvements in Glycemic Control, Weight Loss Among Patients with Type 2 Diabetes

Tirzepatide is a multi-functional peptide based mostly on the native GIP peptide sequence, though it has been modified to bind to each GIP and GLP-1 receptors. It has a imply half-life of roughly 5 days, making once-weekly dosing potential. Drucker mentioned medical trials in sufferers with kind 2 diabetes have proven “very spectacular information,” and the hostile impact (AE) profile just isn’t markedly totally different from different sorts of studies with different molecules on this drug class.

Other presenters outlined the outcomes from the SURPASS trials, all of which confirmed encouraging outcomes with tirzepatide in numerous affected person populations. The SURPASS-1 trial was a randomized, managed, double-blind trial evaluating the outcomes of tirzepatide with placebo in adults with uncontrolled kind 2 diabetes, based on presenter Carol Wysham, MD, a medical professor of medication on the University of Washington School of Medicine.

In the trial, 705 sufferers have been screened and 478 have been randomized between teams to obtain both tirzepatide or a placebo. Within the tirzepatide group, sufferers obtained both 5 mg, 10 mg, or 15 mg, and all 3 doses have been related to a superior discount in A1c in comparison with placebo.

Participants receiving the very best dose achieved a discount of two.7%, and between 87% and 92% of tirzepatide-treated sufferers achieved an A1c goal of lower than 7%. Furthermore, between 13% and 27% of sufferers receiving tirzepatide achieved weight lack of at the least 15% of physique weight, and total AEs have been balanced between the teams. A single dying occurred within the placebo group due to myocardial infarction, based on the researchers.

Based on these findings, Wysham mentioned once-weekly tirzepatide helped handle kind 2 diabetes that was inadequately managed with weight-reduction plan and train alone. Investigators discovered sturdy reductions in glycemic management in addition to physique weight, and normoglycemia (outlined as <5.7%) was achieved in at the least one-third of members.

The SURPASS-2 trial discovered equally encouraging outcomes evaluating tirzepatide with once-weekly semaglutide as an add-on remedy to metformin in sufferers with kind 2 diabetes. Approximately 470 sufferers have been included in every of the 4 remedy teams and between 94% and 96% accomplished the examine.

Discontinuations have been barely larger within the tirzepatide arms in comparison with the semaglutide arm, mentioned presenter Juan Frias, MD, medical director and principal investigator of the National Research Institute in Los Angeles. Frias mentioned nearly all of discontinuations have been attributed to AEs and nearly all of deaths have been associated to COVID-19.

Reductions in A1c have been noticed as early as week 4 within the tirzepatide group and ranged from -0.2% to -0.6% with the 15 mg dose in comparison with semaglutide. A higher proportion of tirzepatide sufferers achieved HbA1c objectives at 40 weeks in comparison with semaglutide and a considerably higher proportion of sufferers within the tirzepatide arm achieved their weight reduction objectives.

Based on these findings, Frias mentioned as soon as weekly tirzepatide demonstrated superior and clinically significant enhancements in glycemic management in addition to a big discount in physique weight. Normoglycemia was achieved in as much as 51% of members.

Finally, Michelle Welch, MD, FACE, president of Diabetes and Metabolism Specialists in San Antonio, mentioned SURPASS-5, which in contrast the efficacy and security of three tirzepatide doses versus placebo as an add-on to insulin glargine with or with out metformin. Participants had a mean age of 60 years, and 44% have been feminine, 80% have been Caucasian, and 18% have been Asian. The common size of diabetes was 13.3 years with a baseline A1c of 8.3%.

Over the 40-week examine interval, investigators noticed between a 2.2% and a pair of.9% lower in A1c within the tirzepatide arm. In the arm receiving placebo and titrated insulin glargine, Welch mentioned there was an anticipated enhance in physique weight with a corresponding lower within the tirzepatide arm. Between 8% and 32% of sufferers achieved 15% or extra physique weight reduction.

All doses of tirzepatide have been superior to placebo at 40 weeks for change from baseline in HbA1c in addition to change from baseline in physique weight. The commonest AEs with tirzepatide have been gastrointestinal in nature, have been largely delicate to average in severity, and decreased over time. Welch concluded that in sufferers with kind 2 diabetes handled with basal insulin glargine and with or with out metformin, tirzepatide was an efficient remedy to enhance glycemic management and decrease physique weight.

Drucker agreed, including that tirzepatide is a promising remedy.

“A considerable variety of persons are having their glucose management normalized on this remedy,” Drucker concluded.


Drucker D, Wysham C, Frias J, Giorgino F, Welch M. Next Chapter in Incretin-Based Therapies–Tirzepatide, a Novel Dual GIP/GLP-1 Receptor Agonist–Results from the First Phase 3 SURPASS Clinical Trials. Presented at American Diabetes Association 81st Scientific Sessions. June 29, 2021. Accessed June 29, 2021. https://ada2021.org/live-stream/19772900/Next-Chapter-in-Incretin-Based-TherapiesTirzepatide-a-Novel-Dual-GIPGLP-1-Receptor-AgonistResults-from-the–First-Phase-3-SURPASS-Clinical-Trials-Includes-Live-Video-Question-and-Answer-Period

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