Tirzepatide bests semaglutide in HbA1c reduction, weight loss

The investigational glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonist tirzepatide led to important and superior HbA1c and physique weight reductions for adults with sort 2 diabetes vs. semaglutide, SURPASS-2 research information present.

Additionally, a prespecified exploratory evaluation confirmed 60% of contributors on the best, 15-mg dose of tirzepatide (Eli Lilly) achieved a composite endpoint of an HbA1c of 6.5% or decrease and weight lack of 10% or higher with no studies of extreme hypoglycemia, in contrast with 22% of contributors assigned 1 mg semaglutide (Ozempic, Novo Nordisk).

“The outcomes of the trial reveal that tirzepatide offered a level of efficacy with respect to HbA1c decreasing and discount in physique weight that has not beforehand been seen in medical trials assessing antihyperglycemic brokers,” Juan Pablo Frias, MD, FACE, medical director and a principal investigator of the National Research Institute in Los Angeles, instructed Healio. “Importantly, these efficacy outcomes had been seen with very low charges of clinically important hypoglycemia and a security and tolerability profile in step with the GLP-1 receptor agonist class.”

Study design

For the part 3 trial, Frias and colleagues analyzed information from 1,879 adults with sort 2 diabetes inadequately managed with metformin remedy of not less than 1,500 mg each day (imply age, 57 years; imply baseline HbA1c, 8.28%; imply baseline weight, 93.7 kg). Researchers randomly assigned contributors a once-weekly subcutaneous injection of 5 mg, 10 mg or 15 mg tirzepatide or 1 mg semaglutide for 40 weeks, adopted by a 4-week security follow-up interval. Primary endpoint was change in HbA1c from baseline to 40 weeks.

The findings had been offered as a late-breaking poster presentation and concurrently printed in The New England Journal of Medicine.

Researchers discovered the estimated imply change from baseline within the HbA1c stage was –2.01 proportion factors, –2.24 proportion factors and –2.3 proportion factors with the 5 mg, 10 mg and 15 mg doses of tirzepatide, respectively, and –1.86 proportion factors with semaglutide. The estimated variations between the 5 mg, 10 mg and 15 mg tirzepatide teams and the semaglutide group had been –0.15 proportion factors (95% CI, –0.28 to –0.03), –0.39 proportion factors (95% CI, –0.51 to –0.26) and –0.45 proportion factors (95% CI, –0.57 to –0.32), respectively.

At all doses, tirzepatide was noninferior and superior to semaglutide. Reductions in physique weight had been higher with tirzepatide vs. semaglutide, with least-squares imply estimated therapy variations of 1.9 kg, 3.6 kg and 5.5 kg for the 5 mg, 10 mg and 15 mg doses, respectively (P < .001 for all).

The most typical hostile occasions had been gastrointestinal and primarily delicate to reasonable in severity within the tirzepatide and semaglutide teams.

Severe hypoglycemia, outlined as blood glucose stage lower than 54 mg/dL, was noticed in 0.6%, 0.2% and 1.7% of contributors within the 5 mg, 10 mg and 15 mg tirzepatide teams, respectively, and in 0.4% of contributors within the semaglutide group.

Serious hostile occasions had been reported in 5% to 7% of the sufferers who acquired tirzepatide and in 3% of those that acquired semaglutide.

“What is stunning is the proportion of sufferers who achieved glorious and even regular glycemic management, with 92% and 51% attaining an HbA1c of lower than 6.5% and fewer than 5.7%, respectively, with the 15 mg tirzepatide dose, in addition to the unprecedented proportion attaining not less than 15% relative discount in physique weight — 40% with the 15 mg tirzepatide dose,” Frias instructed Healio. “And, in all arms of the research, it appeared that weight discount had not plateaued on the finish of the 40-week therapy interval. If accredited, this may probably make tirzepatide essentially the most potent antihyperglycemic agent for sort 2 diabetes, when contemplating glucose and physique weight results.”

A ‘new stage’ of remedy

In a associated editorial, Katherine R. Tuttle, MD, FASN, FACP, FNKF, govt director for analysis at Providence Health Care and professor of medication within the nephrology division on the Institute of Translational Health Sciences on the University of Washington, wrote that the novel idea of mixing a glucose-dependent insulinotropic polypeptide with a GLP-1 receptor agonist “takes incretin therapeutic brokers to a brand new stage.”

“In precept, therapy with a glucose-dependent insulinotropic polypeptide and a GLP-1 receptor agonist collectively would increase glucose decreasing whereas offering protection in opposition to hypoglycemia,” Tuttle wrote. “Thus, in sufferers with sort 2 diabetes, mixture incretin remedy is poised to supply higher glycemic efficacy than therapy with a GLP-1 receptor agonist alone whereas sustaining a great side-effect profile with respect to avoiding hypoglycemia.”

As Healio previously reported, top-line information from SURPASS-4, the biggest and longest trial of this system up to now, additionally demonstrated that tirzepatide considerably lowered HbA1c and physique weight in contrast with insulin glargine (Lantus, Sanofi) for adults with sort 2 diabetes at excessive cardiovascular danger. For the efficacy estimand, the best dose of tirzepatide led to an HbA1c discount of two.58% and lowered physique weight by –11.7 kg in contrast with insulin glargine (imply HbA1c discount of 1.44% and imply weight achieve of 1.9 kg) at 52 weeks. The full outcomes from SURPASS-4 will likely be offered on the European Association for the Study of Diabetes annual assembly and printed in a peer-reviewed journal, in accordance with Eli Lilly.

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