PMID- 37005640 OWN - NLM STAT- MEDLINE DCOM- 20230404 LR - 20230427 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 22 IP - 1 DP - 2023 Apr 1 TI - Combining glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes mellitus (T2DM). PG - 79 LID - 10.1186/s12933-023-01798-4 [doi] LID - 79 AB - Due to their cardiovascular protective effect, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent breakthrough therapies for type 2 diabetes mellitus (T2DM). In this review article, we discuss the mechanistic and clinical synergies that make the combined use of GLP-1RAs and SGLT2is appealing in patients with T2DM. Overall, the presented cumulative evidence supports the benefits of GLP-1RA plus SGLT2i combination therapy on metabolic-cardiovascular-renal disease in patients with T2DM, with a low hypoglycemia risk. Accordingly, we encourage the adoption of GLP-1RA plus SGLT2i combination therapy in patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (i.e., age >/= 55 years, overweight/obesity, dyslipidemia, hypertension, current tobacco use, left ventricular hypertrophy, and/or proteinuria). Regarding renal effects, the evidence of SGLT2is in preventing kidney failure is more abundant than for GLP-1RAs, which showed a beneficial effect on albuminuria but not on hard kidney endpoints. Hence, in case of persistent albuminuria and/or uncontrolled metabolic risks (i.e., inadequate glycemic control, hypertension, overweight/obesity) on SGLT2i therapy, GLP-1RAs should be considered as the preferential add-on therapy in T2DM patients with chronic kidney disease. Despite the potential clinical benefits of GLP-1RA plus SGLT2i combination therapy in patients with T2DM, several factors may delay this combination to become a common practice soon, such as reimbursement and costs associated with polypharmacy. Altogether, when administering GLP-1RA plus SGLT2i combination therapy, it is important to adopt an individualized approach to therapy taking into account individual preferences, costs and coverage, toxicity profile, consideration of kidney function and glucose-lowering efficacy, desire for weight loss, and comorbidities. CI - (c) 2023. The Author(s). FAU - Gourdy, Pierre AU - Gourdy P AD - Endocrinology, Diabetology and Nutrition Department, Toulouse University Hospital, Toulouse, France. gourdy.p@chu-toulouse.fr. AD - Institute of Metabolic and Cardiovascular Diseases, UMR1297 INSERM/UPS, Toulouse University, Toulouse, France. gourdy.p@chu-toulouse.fr. FAU - Darmon, Patrice AU - Darmon P AD - Aix Marseille University, INSERM, INRA, C2VN, Marseille, France. FAU - Dievart, Francois AU - Dievart F AD - Department of Cardiology, Villette Private Hospital, Dunkirk, France. FAU - Halimi, Jean-Michel AU - Halimi JM AD - Department of Nephrology, Tours University Hospital, Tours, France. AD - EA4245, Tours University, Tours, France. FAU - Guerci, Bruno AU - Guerci B AD - Department of Endocrinology, Diabetology, and Nutrition, Brabois Adult Hospital, University of Lorraine, Vandoeuvre-Les-Nancy, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20230401 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - IY9XDZ35W2 (Glucose) RN - 9NEZ333N27 (Sodium) SB - IM MH - Humans MH - Middle Aged MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy/complications MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide-1 Receptor/agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects MH - Overweight MH - Albuminuria/drug therapy MH - Obesity/complications MH - *Hypertension/drug therapy MH - Glucose MH - Sodium MH - *Cardiovascular Diseases/prevention & control PMC - PMC10067319 OTO - NOTNLM OT - Cardiovascular protection OT - Combination therapy OT - Glucagon-like peptide-1 receptor agonists OT - Sodium-glucose cotransporter-2 inhibitors OT - Type 2 diabetes mellitus COIS- PG has received occasional fees, either personally or institutionally, for the activities of speaking, scientific advising, or clinical research from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Novo Nordisk, Organon, Pfizer, and Sanofi. PD has received consulting fees/honoraria from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Mundipharma, Merck Sharp & Dohme, Bayer, Abbott, LVL Medical, and Bastide. FD has received occasional consulting fees/honoraria and travel grants from BMS-Pfizer Alliance, Amgen, AstraZeneca, Bayer, Bouchara-Recordati, Bristol Myers Squibb, Boehringer Ingelheim, Menarini, Merck Sharp & Dohme, Novartis, Novo Nordisk, Organon, Pfizer, Sanofi, and Servier. JMH has received honoraria and/or travel grants from Ablynx, Alexion, AstraZeneca Rare Disease, AstraZeneca, Bayer, Bouchara-Recordati, Fresenius, GlaxoSmithKline, Mundipharma, Merck Sharp & Dohme, Roche, Servier, Sanofi, and Vifor Fresenius. BG has received fees for the activities of speaking, scientific advising, or clinical research from Eli Lilly, Novo Nordisk, AstraZeneca, Sanofi, Bristol Myers Squibb, Novartis, GlaxoSmithKline, Johnson & Johnson, Bayer, Intercept Pharma France, Gilead, Boehringer Ingelheim, Janssen, Intarcia, MetaCure, Pfizer, Merck Sharp & Dohme, Roche Diagnostics, Medtronic, Insulet, A. Menarini Diagnostics, Abbott, LifeScan, Dinno Sante, Asten Sante, Elivie, Homeperf, ISIS Diabete, Linde Homecare France, Nestle, ORKYN', and VitalAire. EDAT- 2023/04/04 06:00 MHDA- 2023/04/04 06:42 PMCR- 2023/04/01 CRDT- 2023/04/03 01:16 PHST- 2023/02/21 00:00 [received] PHST- 2023/03/12 00:00 [accepted] PHST- 2023/04/04 06:42 [medline] PHST- 2023/04/03 01:16 [entrez] PHST- 2023/04/04 06:00 [pubmed] PHST- 2023/04/01 00:00 [pmc-release] AID - 10.1186/s12933-023-01798-4 [pii] AID - 1798 [pii] AID - 10.1186/s12933-023-01798-4 [doi] PST - epublish SO - Cardiovasc Diabetol. 2023 Apr 1;22(1):79. doi: 10.1186/s12933-023-01798-4.