Assessing the benefit–risk profile of newer glucose‐lowering drugs: A systematic review and network meta‐analysis of randomized outcome trials

Dec 26, 2024Diabetes, obesity & metabolism

Benefits and risks of newer diabetes drugs compared using clinical trial results

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Abstract

A total of 198,177 participants were enrolled across 26 trials assessing the benefits and risks of glucose-lowering medications.

GLP-1 receptor agonists (GLP-1RAs) significantly reduced the risks of major adverse cardiovascular events (MACE) and stroke, but were associated with a higher risk of thyroid cancer.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) provided notable reductions in hospitalization for heart failure and improved kidney outcomes, while increasing the risk of genital infections.
Dipeptidyl peptidase 4 inhibitors (DPP4i) correlated with a decreased risk of certain psychiatric disorders and Parkinson's disease, but were linked to higher risks of neuropathy and pancreatitis.
The findings suggest that GLP-1RAs are more effective for reducing vascular complications, whereas DPP4i may offer benefits for neurodegenerative diseases.

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AIM: To comprehensively evaluate the benefits and risks of glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP4i), and sodium-glucose cotransporter 2 inhibitors (SGLT2i).

MATERIALS AND METHODS: A systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 2023 to identify randomized cardiovascular and kidney outcome trials that enrolled adults with type 2 diabetes, heart failure, or chronic kidney disease and compared DPP4i, GLP-1RAs, or SGLT2i to placebo. Twenty-one outcomes (e.g., major adverse cardiovascular events [MACE], stroke, and hospitalization for heart failure [HHF]) were assessed. Data were pooled using population-averaged odds ratios (ORs) with 95% CIs.

RESULTS: Twenty-six trials enrolling 198 177 participants were included. GLP-1RAs were most effective in lowering the risks of MACE (OR, 0.85, [95% CI, 0.79 to 0.92]) and stroke (0.84 [0.77, 0.91]), but increased the risk of thyroid cancer (1.58 [1.36, 2.50]). SGLT2i showed the greatest benefits in reducing the risk of HHF (0.68 [0.64, 0.73]) and improving composite renal outcomes (0.67 [0.58, 0.77]), but increased the risk of genital infections (3.11 [2.15, 4.50]). DPP4i were associated with a lower risk of certain psychiatric disorders, Parkinson's disease (0.54 [0.32, 0.92]), and amputation (0.70 [0.86, 0.93]), but an increased risk of neuropathy (1.10 [1.02, 1.18]) and pancreatitis (1.63 [1.40, 1.91]). The weighted origami plot suggested that GLP-1RAs were more suitable for reducing macrovascular and microvascular outcomes, while DPP4i might be better for neurodegenerative diseases and cancer concerns.

CONCLUSIONS: Given the distinct benefit-risk profiles, the selection of glucose-lowering drugs should be individualized based on patient characteristics and risk factors.

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Assessing the benefit–risk profile of newer glucose‐lowering drugs: A systematic review and network meta‐analysis of randomized outcome trials

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