We have read the article published by Kadowaki, et al. 1 “Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes mellitus in an East Asian population (STEP 6): A randomized, double blind, double dummy, placebo controlled, phase 3a trial”, where the authors conclude that semaglutide at a dose of 2.4 mg, in diabetic and non-diabetic patients, reduces obesity and overweight compared to placebo in East Asian patients. These interesting results, demonstrate once again its benefits regarding overweight and obesity1,2. We consider that there should be several relevant aspects to have in mind. The study shows, once again, that semaglutide might have dose dependent effects and some that aren’t dose dependent, with weight loss being a dose-dependent effect. Regarding renal benefits, we consider that including albuminuria as a variable is of importance, given that only eGFR by CKD-EPI was included in the study. The average eGFR of the patients was 97.2 cc/min, patients with an eGFR less than 30 were excluded (eGFR less than 60 in patients receiving SGLT-2 inhibitors). We mention this since it would’ve been interesting to evaluate albuminuric vs non-albuminuric patients, hence seeing if there are any renal benefits, especially in albuminuric patients that may be dose dependent. Recently, Shaman, et al. 3 reported that liraglutide and semaglutide had renal benefits in type 2 diabetes mellitus, but their effect in albuminuria was higher in patients with 1 mg of semaglutide weekly vs 0.5 mg weekly. The latter allows to hypothesize that this effect may be dose dependent. Given this, it would be of interest to assess if higher doses bring increased renal benefits, as seen in weight loss. In summary, having in mind the renal benefits seen by semaglutide in other studies4, it would be of great importance to verify the impact of albuminuria in patients with obesity. Hence, we hope that in the upcoming trials, albuminuria is taken into consideration, so that we can highlight not only the cardio-metabolic benefits, but renal benefits in diabetic and non-diabetic patients that are obese or overweight, and to assess if there is a dose-dependent response.
Kadowaki T, Isendahl J, Khalid U, Lee SY, Nishida T, Ogawa W, et al. Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population ( STEP 6): a randomized, double-blind, double -dummy, placebo-controlled, phase 3a trial . lancet Diabetes Endocrinol 2022; 10:193-206. https://doi.org/10.1016/S2213-8587(22)00008-0
Wilding J, Batterham R, Calanna S , Davis M, Van Gaal LF, Lingvay I, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021;384:989-1002. https://doi.org/10.1056/NEJMoa2032183
Shaman A, Bain S, Bakris J, Buse J, Idorn T, Mahaffey KW, et at. Effect of Glucagon-Like Peptide-1 Receptor Agonist Semaglutide and Liraglutide Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER. Circulation 2022; 145:575-585. https://doi.org/10.1161/CIRCULATIONAHA.121.055459
Marso E, Bain S, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016; 375:1834-1844 https://doi.org/10.1056/NEJMoa1607141
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