Making a case for the combined use of SGLT2 inhibitors and GLP1 receptor agonists for cardiorenal protection

Abstract

Sodium glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) were initially approved to improve glycemic control in the treatment of type 2 diabetes. Clinical trials have also demonstrated beneficial effects with regards to cardiovascular and renal parameters. Beyond improving glycemic control, these therapies promote weight loss and lower blood pressure when used individually, and in an additive manner when used together. Accordingly, taking advantage of complementary mechanisms of action with the combined use of these two classes of agents to further improve cardiorenal outcomes is conceptually appealing, but has yet to be explored in detail in clinical trials. In this review, we discuss proposed mechanisms for renal protection, clinical benefits, and adverse events associated with the individual and combined use of SGLT2 inhibitors and GLP-1RA. The management of type 2 diabetes has significantly changed over the last few years, moving away from solely glycemic control towards the concurrent management of associated comorbidities in a patient population at significant risk of cardiovascular disease and progression of chronic kidney disease. It is from this perspective that we seek to outline the rationale for the sequential and/or combined use of SGLT2 inhibitors and GLP-1RA in patients with type 2 diabetes.

Phytochemical Profiling in Conjunction with In Vitro and In Silico Studies to Identify Human α-Amylase Inhibitors in Leucaena leucocephala (Lam.) De Wit for the Treatment of Diabetes Mellitus

“…As nutraceuticals, hexadecanoic acid and oleic acid could serve for nonpharmacological strategies for treating T2DM. − However, possible detrimental side effects (e.g., fatty liver, insulin resistance, atherosclerosis, or other cardiovascular diseases) of long-term treatment at higher doses must be considered and would require further animal and human studies. − Moreover, although L. leucocephala leaves could be a reasonable alternative medicine in the form of a food supplement for relief of T2DM, , isolated and purified fatty acids from different plant origins and with proven inhibitory activity of key enzymes related to T2DM − would require optimized production processes at an industrial scale and would have to pass through the entire drug development process, including clinical trials. − …”

Doença Renal Do Diabetes: A Importância Do Diagnóstico E Tratamento Precoces

“…A empaglifozina foi adicionada à terapia individualizada de cada paciente, ou seja, não substituiu os medicamentos que o paciente já fazia uso. Os resultados mostraram que nos pacientes que fizeram o uso da droga, independente da dose, houve uma redução significativa da mortalidade cardiovascular, com redução de 32% da mortalidade geral e diminuição de 35% das internações por insuficiência cardíaca 16,17 . Nos casos de infarto agudo do miocárdio e acidente vascular cerebral não houve digerenças significativas nos desfechos com o uso do fármaco.…”

“…O estudo prosseguiu avaliando-se os resultados renais nesses pacientes os quais a maioria, cerca de 75%, apresentavam uma eTFG (taxa de filtração glomerular estimada) acima de 60 ml / min / 1,73 m² e cerca de 40% apresentavam relação albuminúria/creatinina acima de 30mg/g. Os resultados evidenciaram que os pacientes tratados com empaglifozina demonstraram redução da progressão da doença renal crônica com diminuição da progressão da eTFG de até 4 ml / min / 1,73 m² nas primeiras quatro semanas de tratamento enquanto no grupo que fez uso de placebo houve redução progressiva da eTFG durante o período do estudo 16,17 16 . Partiparam deste estudo pacientes com DM2 e doença cardiovascular estabelecida ou que apresentavam fatores de risco para doenças cardiovasculares 18 .…”

Combining glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes mellitus (T2DM)

“…SGLT2is and GLP-1RAs exhibit clinical benefits on glycemic control, systolic blood pressure (SBP), body weight, and dyslipidemia, which may all partly contribute to the cardiovascular protection provided by these two drug classes [ 4 , 19 ]. Compared to GLP-1RAs, SGLT2is are associated with an overall modest mean weight loss of 2–3 kg [ 20 ]. A network meta-analysis [ 21 ], conducted in 27,018 patients with obesity or overweight and with or without diabetes mellitus, compared the mean weight loss observed with different GLP-1RAs and demonstrated the following trends, from highest to lowest responses: subcutaneous semaglutide at 2.4 mg weekly: − 9.9 kg, liraglutide at > 1.8 mg daily: − 4.5 kg, subcutaneous semaglutide at < 2.4 mg weekly: − 4.3 kg, oral semaglutide: − 2.7 kg, liraglutide at ≤ 1.8 mg daily: − 2.7 kg, extended-release exenatide: − 2.2 kg, immediate-release exenatide: − 1.8 kg, dulaglutide ≥ 1.5 mg: − 1.4 kg, and lixisenatide: − 0.6 kg [ 21 ].…”