GLP1 Receptor Agonist and SGLT2 Inhibitor Combination: An Effective Approach in Real-world Clinical Practice

Díaz-Trastoy, Olaia; Villar-Taibo, Rocío; Sifontes-Dubón, Mildred; Mozo-Peñalver, Hector; Morón, Ignacio; Cabezas-Agrícola, José Manuel; Muñoz-Leira, Virginia; Peinó-García, Roberto; Martis-Sueiro, Aurelio; García-López, José Manuel; Olmos, Miguel

doi:10.1016/j.clinthera.2019.12.012

Cited by 16 publications

(17 citation statements)

References 32 publications

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“…Of note, the combination therapy seems to achieve a sustained glycemic control even over long periods of time while being well tolerated and safe [ 84 ]. These results have been confirmed in real-world population studies [ 85 , 86 ] and by metanalyses performed on available data [ 79 , 87 ]. The dual therapy has demonstrated a greater improvement of endothelial glycocalyx thickness (a marker of endothelial dyfunction) after 12 months of treatment in comparison to insulin therapy, together with a greater reduction in arterial stiffness and a greater increase of myocardial work index, despite a similar improvement of glycemic burden [ 88 ].…”

Section: Sglt-2i Vs Glp-1ra: Direct Comparison and Possible Mechanismssupporting

confidence: 54%

Effects of GLP-1 receptor agonists and SGLT-2 inhibitors on cardiac structure and function: a narrative review of clinical evidence

Natali

Nesti

Tricò

et al. 2021

Cardiovasc Diabetol

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The impressive results of recent clinical trials with glucagon-like peptide-1 receptor agonists (GLP-1Ra) and sodium glucose transporter 2 inhibitors (SGLT-2i) in terms of cardiovascular protection prompted a huge interest in these agents for heart failure (HF) prevention and treatment. While both classes show positive effects on composite cardiovascular endpoints (i.e. 3P MACE), their actions on the cardiac function and structure, as well as on volume regulation, and their impact on HF-related events have not been systematically evaluated and compared. In this narrative review, we summarize and critically interpret the available evidence emerging from clinical studies. While chronic exposure to GLP-1Ra appears to be essentially neutral on both systolic and diastolic function, irrespective of left ventricular ejection fraction (LVEF), a beneficial impact of SGLT-2i is consistently detectable for both systolic and diastolic function parameters in subjects with diabetes with and without HF, with a gradient proportional to the severity of baseline dysfunction. SGLT-2i have a clinically significant impact in terms of HF hospitalization prevention in subjects at high and very high cardiovascular risk both with and without type 2 diabetes (T2D) or HF, while GLP-1Ra have been proven to be safe (and marginally beneficial) in subjects with T2D without HF. We suggest that the role of the kidney is crucial for the effect of SGLT-2i on the clinical outcomes not only because these drugs slow-down the time-dependent decline of kidney function and enhance the response to diuretics, but also because they attenuate the meal-related anti-natriuretic pressure (lowering postprandial hyperglycemia and hyperinsulinemia and preventing proximal sodium reabsorption), which would reduce the individual sensitivity to day-to-day variations in dietary sodium intake.

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Section: Sglt-2i Vs Glp-1ra: Direct Comparison and Possible Mechanismssupporting

confidence: 54%

Effects of GLP-1 receptor agonists and SGLT-2 inhibitors on cardiac structure and function: a narrative review of clinical evidence

Natali

Nesti

Tricò

et al. 2021

Cardiovasc Diabetol

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“…In theory, the combination of SGLT2i with incretin‐based drugs could exert complementary actions on cardiorenal protection and ameliorating adverse effects, with SGLT2i mainly lowering the risks of HF and diabetic nephropathy via hemodynamic benefits, GLP1RA acting to reduce major adverse cardiovascular events with anti‐atherogenic and anti‐inflammatory properties, and DPP4i attenuating the elevated risk of genital infections associated with SGLT2i use through modulating the immune system. 7 , 14 , 18 , 43 , 44 Furthermore, SGLT2i may compensate for the possible negative actions of GLP1RA and potential risk of specific DPP4i in HF progression, while incretin‐based drugs may alleviate the development of ketoacidosis associated with SGLT2i use by counteracting its increased glucagon secretion and subsequent ketogenesis. 14 , 29 , 45 , 46 Nevertheless, it has also been proposed that the production of ketone bodies induced by SGLT2i may partly be responsible for its decrease in cardiac and renal workload, and hence the observed clinical benefits; therefore, any complementary effects of SGLT2i and incretin‐based drug combination may depend on the degree of glucagon suppression, duration of pharmacological treatment, and any changes in drug efficacy over time.…”

Section: Discussionmentioning

confidence: 99%

Switching to Versus Addition of Incretin‐Based Drugs Among Patients With Type 2 Diabetes Taking Sodium‐Glucose Cotransporter‐2 Inhibitors

Lau

Wong

et al. 2022

JAHA

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Background Evidence is limited in comparing treatment modification by substitution or add‐on of glucose‐lowering medications in patients with type 2 diabetes. This observational study aims to compare switching versus add‐on of incretin‐based drugs among patients with type 2 diabetes on background sodium‐glucose cotransporter‐2 inhibitors (SGLT2i). Methods and Results This population‐based, retrospective cohort study was conducted using the IQVIA Medical Research Data, including adults with type 2 diabetes on background SGLT2i from 2005 to 2020. New users of incretin‐based drugs were allocated into the “Switch” group if they had discontinued SGLT2i treatment, or the “Add‐on” group if their background SGLT2i was continued. Baseline characteristics of patients were balanced between groups. Study outcomes were all‐cause mortality, cardiovascular diseases, kidney diseases, hypoglycemia, and ketoacidosis. Patients were observed from the index date of initiating incretin‐based drugs until the earliest of an outcome event, death, or data cut‐off date. Changes in anthropometric and metabolic parameters were also compared between groups from baseline to 12‐month follow‐up. A total of 2888 patients were included, classified into “Switch” (n=1461) or “Add‐on” group (n=1427). Median follow‐up was 18 months with 5183 person‐years. Overall, no significant differences in the risks of study outcomes were observed between groups; however, patients in the “Add‐on” group achieved significantly greater reductions in glycated hemoglobin, weight, percentage weight loss, and systolic blood pressure than their “Switch” counterparts. Conclusions Initiating incretin‐based drugs as add‐on among patients with type 2 diabetes on background SGLT2i was associated with risks of clinical end points comparable to switching treatments, in addition to better glycemic and weight control observed with the combination approach.

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“…There are two methods for initiating combination therapy-sequential initiation and simultaneous initiation. Comparing both methods, simultaneous initiation led to a greater and more rapid reduction in HbA1c and weight, although these differences were unlikely to be significant in the long term [13,14]. The American Diabetes Association (ADA) recommends the sequential initiation of GLP-1 agonist and/or SGLT2 inhibitor in four groups of patients: established atherosclerotic cardiovascular disease, heart failure or chronic kidney disease, obesity and at risk of hypoglycemia.…”

Section: Discussionmentioning

confidence: 99%

High-Dose Liraglutide and SGLT2 Inhibitor: A Promising Combination

Chua

2021

Clinics and Practice

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Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists are important drugs in our armamentarium of treatment for Type 2 diabetes mellitus (DM). In addition to their glucose-lowering effects, they have effects on weight, other metabolic diseases and perhaps most importantly, a cardioprotective and reno-protective effect. Liraglutide is a long-acting GLP-1 agonist which was originally used at 1.8 mg daily for the treatment of DM. However, high-dose liraglutide—liraglutide 3 mg daily, has been demonstrated to be a safe and effective treatment for obesity, with or without DM. In this manuscript, I present two patients who had unusual responses to combination therapy with high-dose liraglutide and SGLT2 inhibitor—marked and/or rapid improvement in glycemic control and weight loss. Drawing from the observations in both cases, I discuss the complementary mechanisms of actions of both drugs, review the clinical effects of combination therapy and distil them into clinical pearls of practical utility for the physician. Given the “clash of the two pandemics” of obesity and COVID-19 and the burgeoning rates of obesity which loom in the near horizon, this is most timely.

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GLP1 Receptor Agonist and SGLT2 Inhibitor Combination: An Effective Approach in Real-world Clinical Practice

Cited by 16 publications

References 32 publications

Effects of GLP-1 receptor agonists and SGLT-2 inhibitors on cardiac structure and function: a narrative review of clinical evidence

Effects of GLP-1 receptor agonists and SGLT-2 inhibitors on cardiac structure and function: a narrative review of clinical evidence

Switching to Versus Addition of Incretin‐Based Drugs Among Patients With Type 2 Diabetes Taking Sodium‐Glucose Cotransporter‐2 Inhibitors

High-Dose Liraglutide and SGLT2 Inhibitor: A Promising Combination

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