Initial SGLT-2 inhibitor/metformin combo yields benefit in T2D

  • Milder TY & al.
  • J Clin Med
  • 4 Jan 2019

  • curated by Miriam Tucker
  • Clinical Essentials
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Takeaway

  • For initial therapy in type 2 diabetes (T2D), combining sodium-glucose cotransporter-2 inhibitor (SGLT-2i) with metformin produces greater HbA1c and weight reductions than either monotherapy, without major safety issues.  

Why this matters

  • Guidelines differ regarding initial combination use.

Study design

  • Meta-analysis, 4 studies, n=3749, randomly allocated to SGLT-2i/metformin vs either alone.
  • Funding: None.

Key results

  • Vs metformin monotherapy, mean change in HbA1c from baseline at weeks 24-26 favored combination for (mean differences [MDs]; 95% CIs):
    • HbA1c: −0.55% (−0.67 to −0.43), and
    • Body weight: −2.00 kg (−2.34 to −1.66).
    • No significant adverse event (AE) differences except greater genital infection risk with combination (4.0% vs 1.8%; relative risk, 2.22; 95% CI, 1.33-3.72).    
  • Vs SGLT-2i monotherapy, MDs (95% CIs) were:
    • HbA1c: −0.59% (−0.72 to −0.46), and
    • Weight: −0.57 kg (−0.89 to −0.25), both favoring combination. 
    • AE differences (relative risks; 95% CIs):
      • Fewer genital infections with combination vs SGLT-2i alone: 4.0% vs 6.1% (0.69; 95% CI, 0.50-0.96) and
      • Higher diarrhea risk with combination: 5.3% vs 2.3% (2.23; 1.46-3.40).
  • No HbA1c difference in high- vs low-dose SGLT-2i (0.02%; 95% CI, −0.08 to 0.13), but slightly greater weight loss (−0.47 kg; −0.88 to −0.06).  

Limitations

  • Small sample.
  • Broad 95% CIs.
  • No control for diet.

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