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Initial Pharmacological Strategies in People with Early Type 2 Diabetes Mellitus: A Systematic Review and Network

Jong Han Choi1, Bo Kyung Koo2, Ye Seul Yang3,4

  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

Diabetes & Metabolism Journal
|April 29, 2025
PubMed
Abstract

Insights

Early combination therapy for type 2 diabetes mellitus (T2DM) significantly improves glycemic control. Metformin combined with GLP-1RA or DPP-4 inhibitors showed the best results with minimal adverse effects.

Area of Science:

  • Endocrinology and Metabolism
  • Pharmacology
  • Clinical Medicine

Background:

  • Type 2 diabetes mellitus (T2DM) necessitates early glycemic control to prevent complications.
  • Optimal early treatment strategies for T2DM are not well-defined.
  • This study evaluates monotherapies versus combination therapies for early T2DM management.

Purpose of the Study:

  • To compare the efficacy and safety of various treatment regimens for early T2DM.
  • To identify the most effective monotherapies and combination therapies for glycemic control.
  • To assess the impact on body weight and adverse events.

Main Methods:

  • Systematic review and network meta-analysis adhering to PRISMA guidelines.
  • Inclusion of randomized controlled trials assessing glycemic control, body weight, and adverse events.
  • Primary outcomes: change in glycosylated hemoglobin (HbA1c) and achievement of target HbA1c at 6 months.

Main Results:

  • Combination therapies demonstrated superior efficacy compared to monotherapy.
  • Metformin + GLP-1RA (glucagon-like peptide-1 receptor agonists) and Metformin + DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors) were most effective for HbA1c reduction.
  • GLP-1RA and SGLT2 inhibitors (sodium-glucose cotransporter-2 inhibitors) promoted weight loss; sulfonylureas increased hypoglycemia risk, with other adverse events comparable across regimens.

Conclusions:

  • Early introduction of combination therapy for T2DM offers significant glycemic benefits without substantially increasing risks.
  • Further research into novel combination therapies, particularly with potent GLP-1RAs, is warranted.
Keywords:
Diabetes mellitus, type 2Drug therapy, combinationGlycemic controlHypoglycemic agents

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