Efficacy and safety of variable-dose metformin as adjunctive therapy to insulin in adolescents with type 1 diabetes mellitus: a systematic review and network meta-analysis
Abstract
Background: Adolescent Type 1 Diabetes (T1D) is complicated by insulin resistance, dyslipidemia, and heightened cardiovascular risk. As adjunctive metformin therapy lacks optimized dosing, we conducted a network meta-analysis (NMA) to rigorously assess the dose-dependent efficacy and safety of metformin combined with insulin in this population.
Methods: Totally 764 adolescents (aged 10-19 years) met inclusion criteria were involved. We assessed five metformin regimens: 1.0 g/day, 1.7 g/day, 2.0 g/day, weight-based (≤ 60 kg:1.0 g/day;≥60 kg:2.0 g/day), and multi-tiered weight-based (< 50 kg:1.0 g;50-75 kg:1.5 g;≥75 kg:2.0 g). Outcomes included HbA1c, BMI/BMI-Z, insulin dose, lipid profile, and adverse events. A Bayesian NMA was performed using R 4.4.1, with effect sizes reported as mean differences (MD) or relative risks (RR) with 95% confidence intervals (CI). Surface under the cumulative ranking curve (SUCRA) values ranked interventions.
Results: Consequently, metformin 2.0 g/day significantly reduced BMI (MD=-0.6 kg/m², 95%CI:-0.68, -0.52) and LDL-C (MD=-12.78 mg/dL, 95%CI:-21.17, -0.49) versus placebo. Doses of 1.0 g/day, 2.0 g/day, and the 60 kg weight-based regimen significantly reduced daily insulin requirements. Metformin 2.0 g/day and the 50 kg weight-based regimen reduced total cholesterol. No regimen significantly lowered HbA1c or triglycerides versus placebo. All doses demonstrated safety profiles comparable to placebo regarding gastrointestinal events,…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 764 participants or records.
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.