The discovery of new and better ways to treat obesity and type 2 diabetes is evolving at a rapid pace, with more treatment strategies emerging that simulate the action of our own hormones.   Two hormones that are of interest include GLP1, and GIP.  Both are ‘incretin’ hormones that are released from our intestines in response to eating.  In the past week, a new publication and a new topline data release add to our knowledge of these hormonal approaches to treatment of obesity and type 2 diabetes.


The STEP2 study of semaglutide 2.4mg as an obesity treatment in people with type 2 diabetes was published in The Lancet (disclaimer: I am a co-author of this paper).   Semaglutide is a GLP1 analog that has been in use since 2018 as a treatment of type 2 diabetes, at a lower dose of 1.0mg (called Ozempic).  In this study, we randomized 1,210 people with type 2 diabetes and overweight or obesity (BMI ≥27) to receive either once weekly semaglutide 2.4mg, semaglutide 1.0mg, or placebo.  At baseline, the mean weight was 99.8kg (BMI 35.7), average hemoglobin A1C was 8.1%, and patients were on up to 3 oral diabetes medications (about 25% were on sulfonylurea).  At 68 weeks, mean weight loss was -9.6% with semaglutide 2.4mg, vs -7.0% with semaglutide 1.0mg, vs -3.4% with placebo (differences between groups were statistically significant).  Diabetes control improved in all three groups, with A1C reduction of -1.6% with semaglutide 2.4mg, -1.5% with semaglutide 1.0mg, and -0.4% with placebo. A decrease in use of concomitant glucose lowering medication was enjoyed by 29% of patients with semaglutide 2.4mg, 25% of patients with semaglutide 1mg, and 7% of patients with placebo.


This past week, the topline results were also released for the SURPASS-2 trial, comparing tirzepatide to semaglutide as treatments of type 2 diabetes.  As blogged previously, tirzepatide is a dual GLP1 and GIP agonist that is being studied for treatment of type 2 diabetes, as well as as a weight loss medication in people with or without diabetes.  In the SURPASS-2 trial, 1,879 participants with type 2 diabetes on metformin alone were randomized to receive either tirzepatide 5mg, 10mg, or 15mg weekly, or semaglutide at the 1.0mg weekly (diabetes treatment) dose. Baseline A1C in these participants was 8.3%, and mean baseline weight was 93.7kg.  After 40 weeks, they found an A1C reduction with tirzepatide 5mg of -2.1%, -2.4% with tirzepatide 10mg, -2.5% with tirzepatide 15mg, vs -1.9% with semaglutide 1mg (all were statistically significant compared to semaglutide).  Weight loss was -8.5% with tirzepatide 5mg, -11% with tirzepatide 10mg, -13.1% with tirzepatide 15mg, and -6.7% with semaglutide 1mg (all were statistically significant compared to semaglutide). The most common side effects for both tirzepatide and semaglutide were gastrointestinal (GI), and a little bit more common with tirzepatide 15mg than with semaglutide 1mg. Discontinuation rates due to adverse events were 7.9% with tirzepatide 15mg, vs 3.8% with semaglutide 1mg.


To better understand how these medications compare as weight loss agents, we would need to compare tirzepatide to the obesity treatment dose of semaglutide (2.4mg), a study which has not (yet) been done.  As always, we should not compare numbers between the two separate trials, due to differences in population, baseline medications, study design, primary endpoints, etc.


As a clinician, I look very forward to both semaglutide 2.4mg and tirzepatide becoming available for people with (and without!) type 2 diabetes.  Both of these medications show the capacity for excellent weight loss in people with type 2 diabetes (and more than any currently available obesity treatments), a group of people in whom it is harder to lose weight than people without diabetes (stay tuned for an upcoming blog to explore this phenomenon further). Different medications will work best for different people, and it is great to have options.  There are other exciting treatments coming down the pipes as well… stay tuned!


Disclaimer: I am an investigator in the STEP and SURPASS clinical trial programs.  The STEP trials are conducted by Novo Nordisk, the makers of semaglutide.  The SURPASS trials are conducted by Eli Lilly, the makers of tirzepatide. I receive honoraria as a continuing medical education speaker and consultant from the makers of semaglutide (Novo Nordisk) and tirzepatide (Eli Lilly).


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