Dimitrios Patoulias1, Konstantinos Stavropoulos2, Konstantinos Imprialos1, Alexandra Katsimardou1, Maria-Styliani Kalogirou1, Konstantinos Koutsampasopoulos1, Ioanna Zografou1, Christodoulos Papadopoulos3, Asterios Karagiannis1, Michael Doumas4. 1. Second Propedeutic Department of Internal Medicine, General Hospital "Hippokration", Aristotle University of Thessaloniki, Thessaloniki, Greece. 2. Second Propedeutic Department of Internal Medicine, General Hospital "Hippokration", Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address: konvstavropoulos@hotmail.com. 3. Third Department of Cardiology, General Hospital "Hippokration", Aristotle University of Thessaloniki, Thessaloniki, Greece. 4. Second Propedeutic Department of Internal Medicine, General Hospital "Hippokration", Aristotle University of Thessaloniki, Thessaloniki, Greece; VAMC and George Washington University, Washington, DC, USA.
Abstract
OBJECTIVE: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now considered as key players in the treatment of type 2 diabetes mellitus (T2DM). The purpose of this meta-analysis was to provide precise effect estimates regarding the safety and efficacy of the addition of a GLP-1RA on top of SGLT-2i treatment. RESEARCH DESIGN AND METHODS: PubMed and CENTRAL, along with grey literature sources, were searched from their inception to May 2019 for randomized controlled trials (RCTs) with a duration ≥ 12 weeks, evaluating the safety and efficacy of addition of a GLP-1RA on a SGLT-2i compared to SGLT-2i alone in patients with T2DM. We also used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the credibility of our summary estimates. RESULTS: We identified three eligible RCTs, pooling data retrieved from 1,042 patients with T2DM in total. Administration of the maximum dose of a GLP-1RA on top of SGLT-2i treatment compared to SGLT-2i alone resulted in significant decrease in HbA1c by 0.91% (95% CI; -1.41 to -0.42) [GRADE: moderate], in body weight by 1.95 kg (95% CI; -3.83 to -0.07) [GRADE: moderate], in fasting plasma glucose by 1.53 mmol/L (95% CI; -2.17 to -0.88) [GRADE: moderate] and in systolic blood pressure levels by 3.64 mm Hg (95% CI -6.24 to -1.03). No significant effects on lipid profile and diastolic blood pressure were demonstrated. A significant increase in the risk for any hypoglycemia (RR: 2.62, 95% CI; 1.15-5.96, I2 = 33%) [GRADE: moderate] and for nausea (RR: 3.21, 95% CI; 1.36-7.54, I2 = 63%) [GRADE: moderate] and a non-significant increase in the risk for diarrhoea (RR: 1.64, 95% CI; 0.98-2.75, I2 = 0%) [GRADE: low] were documented. No other safety issues were identified. CONCLUSIONS: This meta-analysis suggests that a GLP-1RA/SGLT-2i combination, if tolerated, exerts significant beneficial effects on glycemic control and body weight loss, however increasing the risk for any hypoglycemia and gastrointestinal adverse events.
OBJECTIVE:Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are now considered as key players in the treatment of type 2 diabetes mellitus (T2DM). The purpose of this meta-analysis was to provide precise effect estimates regarding the safety and efficacy of the addition of a GLP-1RA on top of SGLT-2i treatment. RESEARCH DESIGN AND METHODS: PubMed and CENTRAL, along with grey literature sources, were searched from their inception to May 2019 for randomized controlled trials (RCTs) with a duration ≥ 12 weeks, evaluating the safety and efficacy of addition of a GLP-1RA on a SGLT-2i compared to SGLT-2i alone in patients with T2DM. We also used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the credibility of our summary estimates. RESULTS: We identified three eligible RCTs, pooling data retrieved from 1,042 patients with T2DM in total. Administration of the maximum dose of a GLP-1RA on top of SGLT-2i treatment compared to SGLT-2i alone resulted in significant decrease in HbA1c by 0.91% (95% CI; -1.41 to -0.42) [GRADE: moderate], in body weight by 1.95 kg (95% CI; -3.83 to -0.07) [GRADE: moderate], in fasting plasma glucose by 1.53 mmol/L (95% CI; -2.17 to -0.88) [GRADE: moderate] and in systolic blood pressure levels by 3.64 mm Hg (95% CI -6.24 to -1.03). No significant effects on lipid profile and diastolic blood pressure were demonstrated. A significant increase in the risk for any hypoglycemia (RR: 2.62, 95% CI; 1.15-5.96, I2 = 33%) [GRADE: moderate] and for nausea (RR: 3.21, 95% CI; 1.36-7.54, I2 = 63%) [GRADE: moderate] and a non-significant increase in the risk for diarrhoea (RR: 1.64, 95% CI; 0.98-2.75, I2 = 0%) [GRADE: low] were documented. No other safety issues were identified. CONCLUSIONS: This meta-analysis suggests that a GLP-1RA/SGLT-2i combination, if tolerated, exerts significant beneficial effects on glycemic control and body weight loss, however increasing the risk for any hypoglycemia and gastrointestinal adverse events.