Abstract
GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) have been associated with improved glycemic control, body weight loss and favorable changes in cardiovascular risk factors and outcomes. We conducted a systematic review and meta-analysis to evaluate the effects of the addition of GLP-1RA to SGLT2i in patients with type 2 diabetes mellitus and inadequate glycemic control. Six databases were searched until March 2019. Randomized controlled trials (RCT) with a follow-up of at least 24 weeks reporting on HbA1c, body weight, systolic blood pressure, lipids, achievement of HbA1c < 7%, requirement of rescue therapy due to hyperglycemia and hypoglycemic events were selected. Four RCTs were included. Compared to SGLT2i, the GLP-1RA/SGLT2i combination was associated with greater reduction in HbA1c (−0.74%), body weight (−1.61 kg), and systolic blood pressure (−3.32 mmHg). A higher number of patients achieved HbA1c < 7% (RR = 2.15), with a lower requirement of rescue therapy (RR = 0.37) and similar incidence of hypoglycemia. Reductions in total and LDL cholesterol were found. The present review supports treatment intensification with GLP-1RA in uncontrolled type 2 diabetes on SGLT2i. This drug regimen could provide improved HbA1c control, together with enhanced weight loss and blood pressure and lipids control.
Highlights
In the last 10 years, two new drug classes have been available for type 2 diabetes therapy, GLP-1 receptor agonists (GLP-1RA) and SGLT-2 inhibitors (SGLT2i)
Since studies evaluating the effects of the addition of GLP-1RA to SGLT2i in patients with inadequately controlled type 2 diabetes are available, we performed a systematic review and meta-analysis focusing on traditional glycemic targets as well as on other major risk factors for cardiovascular disease, including hypertension, obesity, and dyslipidemia
This systematic review and meta-analysis was performed to identify a high level of evidence on the efficacy of the combination therapy with GLP-1RA and SGLT2i versus SGLT2i in patients with inadequately controlled type 2 diabetes
Summary
In the last 10 years, two new drug classes have been available for type 2 diabetes therapy, GLP-1 receptor agonists (GLP-1RA) and SGLT-2 inhibitors (SGLT2i). The most used SGLT2i include canagliflozin, dapagliflozin and empagliflozin They inhibit glucose reabsorption by the kidney, increasing its excretion in the urine and ameliorating the effects of glucotoxicity on beta-cells; they increase glucagon levels. SGLT2i combination should be preferentially used over other therapies in inadequately controlled patients in which promoting weight loss is a priority[14] Considering their specific mechanistic synergy, tackling multiple pathophysiological defects of type 2 diabetes, the combination of GLP-1RA and SGLT-2i is expected to result in further decrease in HbA1c with no further risk of hypoglycaemia, greater weight loss, and enhanced potential for cardiovascular and renal benefits, as compared with either drug class alone. A comparison of the effects of the GLP-1RA/SGLT2i combination versus SGLT2i on HbA1c, body weight, systolic blood pressure (SBP), lipids, achievement of HbA1c < 7%, requirement of rescue therapy due to hyperglycemia, and incidence of hypoglycemic events was carried out
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