[Comment] Can oral GLP-1 receptor agonists ACHIEVE the same as SGLT2 inhibitors?

Can oral GLP-1 receptor agonists ACHIEVE the same as SGLT2 inhibitors? Affiliations & Notes aDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, Netherlands bThe George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia Article Info Publication History: Published June 8, 2026 DOI: 10.1016/S0140-6736(26)01040-8 External LinkAlso available on ScienceDirect External Link Copyright: © 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies. Download started OkPharmacotherapy for the treatment of type 2 diabetes has changed profoundly. SGLT2 inhibitors and GLP-1 receptor agonists are now well recognised for their improvements in metabolic control and, importantly, cardiovascular and kidney protective effects.1 As a consequence, the glucose-centric treatment paradigm for individuals living with diabetes has shifted towards a treatment strategy focused on microvascular and macrovascular protection. Early treatment recommendations highlighted the complementary aspects of both drug classes: SGLT2 inhibitors primarily for heart failure and kidney protection; GLP-1 receptor agonists for atherosclerotic cardiovascular disease prevention. Yet, this separation is becoming increasingly inadequate as more recent studies have shown that GLP-1 receptor agonists also improve heart failure symptoms and slow the progression of kidney disease.1 Furthermore, the clinical availability of oral GLP-1 receptor agonists offers an opportunity that has the potential to enhance the adoption of GLP-1 receptor agonist treatment beyond what has been achievable with SGLT2 inhibitors alone. Against this background, the ACHIEVE-2 trial, presented by Michelle Welch and colleagues in The Lancet and comparing head to head the SGLT2 inhibitor dapagliflozin with the oral GLP-1 receptor agonist orforglipron, is of interest.2 References 1. Brown, E ∙ Heerspink, HJL ∙ Cuthbertson, DJ ∙ et al. SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications Lancet. 2021; 398:262-276 2. Welch, M ∙ Forst, T ∙ Weiping, J ∙ et al. Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial Lancet. 2026; published online June 8. https://doi.org/10.1016/S0140-6736(26)00800-7 3. Nauck, MA ∙ Tuttle, KR ∙ Tschöp, MH ∙ et al. Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits Lancet. 2026; 407:892-908 4. Heerspink, HJ ∙ Perkins, BA ∙ Fitchett, DH ∙ et al. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications Circulation. 2016; 134:752-772 5. Powell-Wiley, TM ∙ Poirier, P ∙ Burke, LE ∙ et al. Obesity and cardiovascular disease: a scientific statement from the American Heart Association Circulation. 2021; 143:e984-1010 6. Apperloo, EM ∙ Neuen, BL ∙ Fletcher, RA ∙ et al. Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials Lancet Diabetes Endocrinol. 2024; 12:545-557 7. Neuen, BL ∙ Fletcher, RA ∙ Heath, L ∙ et al. Cardiovascular, kidney, and safety outcomes with GLP-1 receptor agonists alone and in combination with SGLT2 inhibitors in type 2 diabetes: a systematic review and meta-analysis Circulation. 2024; 150:1781-1790 8. Horn, DB ∙ Aronne, LJ ∙ Wharton, S ∙ et al. Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial Lancet. 2026; published online May 12. https://doi.org/10.1016/S0140-6736(26)00656-2