Glucagon-like peptide-1 receptor agonists or sodium–glucose cotransporter-2 inhibitors as add-on therapy for patients with type 2 diabetes? A systematic review and meta-analysis of surrogate metabolic endpoints

May 22, 2020Diabetes & metabolism

Comparing two add-on diabetes medicines on metabolic markers in type 2 diabetes

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Abstract

Administration of GLP-1 receptor agonists (GLP-1RAs) resulted in significant decreases in HbA1c compared to sodium-glucose cotransporter-2 inhibitors (SGLT-2is).

GLP-1RAs are associated with a higher likelihood of achieving an HbA1c level of less than 7% compared to SGLT-2is.
No significant differences in body weight reduction of more than 5% were found between GLP-1RAs and SGLT-2is.
The use of GLP-1RAs increased the risk of any hypoglycaemia, nausea, and diarrhoea.
GLP-1RAs were linked to a lower risk of genital infections compared to SGLT-2is.
No notable differences in severe hypoglycaemia, treatment discontinuation, or blood pressure levels were identified between the two treatments.

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OBJECTIVE: As sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are second-line treatment options in type 2 diabetes mellitus (T2DM), our study sought to provide precise effect estimates regarding the role of GLP-1RAs vs SGLT-2is as add-on treatments in patients uncontrolled by metformin monotherapy.

RESEARCH DESIGN AND METHODS: PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and 'grey literature' were searched from their inception up to December 2019 for randomized controlled trials (RCTs) with durations≥12weeks to evaluate the safety and efficacy of adding a GLP-1RA vs an SGLT-2i in patients with T2DM.

RESULTS: Three eligible RCTs were identified. Administration of GLP-1RAs vs SGLT-2is resulted in significant decreases in HbA1c with no significant impact on either body weight or fasting plasma glucose. GLP-1RA treatment led to a significant increase in odds for achieving an HbA1c<7% compared with SGLT-2is, whereas no difference was detected in body weight reductions of>5%. Significantly greater risk for any hypoglycaemia, nausea and diarrhoea, and lower risk for genital infections, was also observed with GLP-1RAs, while no differences regarding severe hypoglycaemia, treatment discontinuation and impact on blood pressure levels were identified. No other major safety issues arose.

CONCLUSION: Our meta-analysis suggests that GLP-1RAs provide better glycaemic effects than SGLT-2is in patients with T2DM uncontrolled by metformin, albeit while increasing risk for hypoglycaemia and gastrointestinal adverse events.

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Glucagon-like peptide-1 receptor agonists or sodium–glucose cotransporter-2 inhibitors as add-on therapy for patients with type 2 diabetes? A systematic review and meta-analysis of surrogate metabolic endpoints

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